THE PHYSIOLOGY
OF REPRODUCTION

v

FRANCIS H^Af MARSHALL

Sc.D. (CAMB.), D.Sc. (EDIN.), F.R.S.

FELLOW OF CHRIST'S COLLEGE, AND READER IN AGRICULTURAL PHYSIOLOGY
IN THE UNIVERSITY OF CAMBRIDGE

WITH CONTRIBUTIONS BY

WILLIAM CRAMER, PH.D., D.Sc., M.R.C.S., L.R.C.P.
JAMES LOCHHEAD, O.B.E., M.A., M.D., F.R.C.S.E.

AND

CRESSWELL SHEARER, M.D., Sc.D., F.R.S.

SECOND AND REVISED EDITION

^ /

^

<x*

LONGMANS, GREEN, AND CO.

39 PATERNOSTER ROW, LONDON, E.C.4

NEW YORK, TORONTO
BOMBAY, CALCUTTA, AND MADRAS

1922
All rights reserved

Made in Great Britain

TO
WALTER HEAPE, ESQ., M.A., F.R.S.

PREFACE TO SECOND EDITION

IN preparing a new edition of "The Physiology of Reproduction"
(the first edition having been for some time out of print) an attempt
has been made to bring the book up to date, and much new matter
has been added. Dr. Cramer has enlarged and partly rewritten his
chapter on the "Biochemistry of the Sexual Organs," besides per-
forming a similar service in respect of Dr. Lochhead's chapter
on the " Changes in the Maternal Organism During Pregnancy," to
which many important additions have been made ; Dr. Lochhead,
unfortunately, owing to his professional duties at Gibraltar, having
been unable to revise his former contributions. The chapter on
" Foetal Nutrition and the Physiology of the Placenta," by the
latter author, has been reprinted practically as it originally stood,
excepting for certain slight additions, chiefly in the form of footnotes,
for which I am responsible. It is believed, however, that the chapter
is in no sense out of date, since the quantity of original work
done in this field during the last decade has been relatively small.
Dr. Shearer has added to the value of the chapter on " Fertilisation "
by including a description of the Oxidation Processes Occurring in
the Egg at and after Fertilisation, as well as an account of Child's
work on the Life Cycle ; he has also given me the benefit of his
wide knowledge of the literature in the revision of other parts of
the book. In addition to Dr. Cramer and Dr. Shearer, I wish also
especially to thank my colleague, Mr. John Hammond, for his valuable
and ready help in the preparation of this edition. Besides affording
me the advantage of his extensive knowledge and experience, he
has placed at my disposal his numerous notes relating to different
branches of Generative Physiology.

I have pleasure in expressing my obligations to those authors,
editors, and publishers who have permitted me to reproduce illustra-
tions from their respective works; in particular I must mention
Professor E. Steinach, of Vienna; Dr. A. Pezard, of Paris; and
Dr. H. D. Goodale, of Amherst, Mass., U.S.A. I am indebted also

viii PREFACE

to the following for help in revising the proofs, for supplying me
with important references, or for assistance in other ways : — Professor
J. T. Wilson, of Cambridge ; Professor C. G. Seligman, of London ;
Dr. W. Blair Bell, of Liverpool; Mr. H. M. Fox, of Gonville and
Caius College; Dr. A. C. Haddon, of Christ's College: Mr. K. J. J.
Mackenzie, of Christ's College; Mr. L. F. Messel, of Magdalene
College : Mr. M. S. Pease, of Trinity College ; Dr. It. H. Rastall, of
Christ's College ; Mr. H. G. Sanders, of St. John's College ; Mr. J. T,
Saunders, of Christ's College ; Dr. J. M. Duncan Scott, of Edinburgh ;
and Mr. R. Weatherall, of Christ's College. To Mr. Alan S. Parkes,
of Christ's College, I am under a special obligation for the great
trouble he has taken in preparing the indices and reading the final
proof sheets.

I wish further to express my gratitude to Messrs. Longmans,
Green, & Co. for having met my wishes in all possible respects in
matters connected with publication.

The introduction to the first edition is reprinted as it originally
stood, except for a few necessary corrections.

It is now more than twenty-two years since, in association with
Professor Cossar Ewartiand Professor (now Sir Edward) Sharpey
Schafer at Edinburgh, I began the series of investigations on the
oastrous cycle from which the present work has grown, and I take
this further opportunity of thanking all who helped me in those
early days. Particularly I must mention Lord Carmichael of Skirling,
without whose generosity it would, in the absence of a regular
endowment, have been impossible to have conducted researches on
so extensive a scale. Since 1908 the work has been continued at
Cambridge, and I wish also to thank my colleagues in the schools
of Agriculture and Physiology, as well as the Master and Fellows of
my own college, for all they have done to make that work possible,
and for their never-failing encouragement during the past fourteen
years.

F. H. A. MARSHALL.

CHRIST'S COLLEGE, CAMBRIDGE,
August 1922.

CONTENTS

.. PAGK

INTRODUCTION 1

CHAPTER I

THE BREEDING SEASON 4

Protozoa — Ccelenterata — Nemertea, Etc. — Annelida — Arthropoda —
Mollusca — Echinodermata — Cephalochordata — Pisces — Amphibia —
Reptilia — Aves — Mammalia — Associated Phenomena — Periodicity of
Breeding, Etc.

CHAPTER II

THE (ESTROUS CYCLE IN THE MAMMALIA - - 32

Monotrenmta — Marsupialia — Rodentia — Ungulata — Cetacea — Garni vora
— Insectivora — Cheiroptera — Primates.

CHAPTER III

THE CHANGES THAT OCCUR IN THE NON-PREGNANT UTERUS DURING THE

(ESTROUS CYCLE • 70

The Cycle in Man — Monkeys — Lemurs — Insectivores — Carnivores —
Rodents — Ungulates — Marsupials.

CHAPTER IV

CHANGES IN THE OVARY — OOGENESIS — GROWTH OF FOLLICLES — OVULATIOTJtT-
FORMATION OF CORPORA LUTEA AND ATRETIC FOLLICLES — THE SIGNIFI-
CANCE OF THE PROOiSTROUS CHANGES IN THE UTERUS - 109

Development of Ovary and Oogenesis — Maturation and Ovulation — The
Formation of the Corpus Luteum — The Atretic Follicle — Super-
fcetation — Formation of Ova — The Significance of the Prooestrous
Changes.

CHAPTER V

SPERMATOGENESIS — INSEMINATION 159

Structure of Spermatozoa — Seminal Fluid — Movements of Spermatozoa —
Insemination.

CHAPTER VI

FERTILISATION - 180

The Oxidation Processes of the Ovum in Fertilisation and During Early
Development — The Hereditary Effects of Fertilisation — Telegony —
On Gametic Selection and the Conditions Favourable for the Occur-
rence of Fertilisation — Conjugation in the Protozoa — The Supposed
Chemotactic Properties of Spermatozoa and their Relation to the
Phenomena of Fertilisation — Child's Theory of the Life Cycle —
Artificial Aids to Fertilisation — Parthenogenesis, Natural and
Artificial.

x CONTENTS

CHAPTER VII

1'AWK
THE ACCESSORY REPRODUCTIVE ORGANS OF THE MALE AND THE MECHANISMS

CONCERNED* IN INSEMINATION - - 239

The Vesicula? Seminales — The Prostate Gland — Cowper's Glands — The
Copulatory Organ — The Mechanisms of Erection, Ejaculation, and
Retraction.

CHAPTER VIII

THE BIOCHEMISTRY OF THE SEXUAL ORGANS - 273

The Female Generative Organs : Mammals, Birds, Lower Vertebrates,
Invertebrates — The Male Generative Organs : The Semen — The
Chemistry of the Spermatozoon — The Biochemistry of Fertilisation.

CHAPTER IX

THE TESTICLE AND THE OVARY AS ORGANS OF INTERNAL SECRETION 320

The Correlation between the Testis and the other Male Organs and
Characters — The Correlation between the Ovary and the other
Female Organs and Characters — The Factors which Determine the
Occurrence of Heat and Menstruation — The Function of the Corpus
Luteum — The Supposed Internal Secretion of the Uterus — The
Correlation between the Generative Organs and the Ductless Glands
— General Conclusions regarding the Internal Secretions of the
Ovary and the Testis — The Influence of the Reproductive Organs
and the Effects of Castration upon the General Metabolism.

CHAPTER X

FCETAL NUTRITION : THE PLACENTA - 393

Part I. The Placenta as an Organ of Nutrition — I. Historical Survey —
II. Structure and Functions of the Epithelial Investment of the Villi
—III. The Decidua.

Part II. The first Stages of Pregnancy : Placental Classification — I. The
Ovarian Ovum — II. The Fertilised Ovum and its Coverings — III. The
Uterine Mucosa — IV. Placental Classification.

Part III. The Foetal Membranes, the Yolk-sac, and the Placenta —
I. General Anatomy of the Foetal Membranes — II. The Nutritive
Importance of the Yolk-sac (Marsupialia, Ungulata, Carnivora,
Proboscidea and Hyrax, Rodentia, Insectivora, Primates) — -III. The
Placenta in Indeciduata (Ungulata, Lemuroidea, Cetacea, Sirenia, and
Edentata) — IV. The Placenta in Deciduata (Carnivora, Proboscidea,
Hyrax, Rodentia, Insectivora, Cheiroptera, Primates) — V. General
Considerations of Fcetal Nutrition and the Placenta : A . The Plan
of Placental Formation. B. The Nature of the Trophoblastic
Activity.

CHAPTER XI

THE CHANGES IN THE MATERNAL ORGANISM DURING PREGNANCY - 514

I. The Stimulus for the Maternal Changes during Pregnancy — II. Changes
in the Metabolism of the Mother during Pregnancy : A . The Source
of the Materials transferred to the New Organism. B. The Body-
Weight during Pregnancy. C. The Protein Metabolism in Pregnancy.
D. The Carbohydrate Metabolism in Pregnancy. E. The Metabolism
of Fats in Pregnancy. F. The Acid-Base Equilibrium in Pregnancy.
<?. The Metabolism of Metals and Salts in Pregnancy. H. Respira-
tory Exchange and Energy Metabolism during Pregnancy.
7. Summary. K. Analogy oetween Metabolism of Pregnant and
Tumour-bearing Animals — III. The Changes in the Maternal Tissues
during Pregnancy.

CONTENTS xi

CHAPTER XII

PAGE

THE INXERVATION OF THE FEMALE GENERATIVE ORGAN'S — UTERINE CON-
TRACTION— PARTURITION — THE PUERPERAL STATE ... 560

The Innervation of the External Generative Organs — The Innervation
of the Ovaries — The Innervation of the Uterus and Vagina and the
Mechanism of Uterine Contraction — The Normal Course of Parturi-
tion in the Human Female — Parturition in other Mammalia — The
Nervous Mechanism of Parturition— Changes in the Maternal
Organism — The Cause of Birth — Prolonged Gestation — The
Puerperium.

CHAPTER XIII

LACTATION -

.Structure of the Mammary Glands — The Composition and Properties
of Milk — The Influence of Diet and other Factors on the Composition
and Yield of Milk — The Duration of Lactation — The Discharge of
Milk — The Formation of the Organic Constituents of Milk — The
Normal Growth of the Mammary Glands — The Factors which are
concerned in the Processes of Mammary Growth and Secretion.

CHAPTER XIV

FERTILITY -

Effect of Age — Effects of Environment and Nutrition — Effect of Pro-
longed Lactation — Influence of the Male Parent — Effect of Drugs
— Effects of In-Breeding and Cross-Breeding — Inheritance of Fertility
— Certain Causes of Sterility — Artificial Insemination as a Means
of overcoming Sterility — Abortion — The Increase of Fertility, a
Problem of Practical Breeding — The Birth-rate in Man.

CHAPTER XV

THE FACTORS WHICH DETERMINE SEX 661

( 1 ) Theories which assume that Sex-determination takes place subsequently
to Fertilisation — (2) Theories which assume that Sex-determination
takes place at the time of Fertilisation or previously to Fertilisation
— (3) Theories which limit Sex-determination to no particular perit>d
of development, or which assert that Sex may be established at
different periods — Hermaphroditism and Sexual Latency — General
Conclusions.

CHAPTER XVI

PHASES IN THE LIFE OF THE INDIVIDUAL — THE DURATION OF LIFE AND THE

CAUSE OF DEATH - - 701

Growth of the Body before Birth — Growth of the Body after Birth —
Puberty — The Menopause — Senescence — The Duration of Life and
the Cause of Death.

INDEX OF SUBJECTS 729

INDEX OF AUTHORS - - - 759

ILLUSTRATIONS

1. Diagram illustrating the " Wellenbewegung " hypothesis - - 62

2. Transverse section through Fallopian tube, showing folded epithelium and

muscular coat - • - 70

3. Reproductive organs of ewe - - 71

4. Section of a cornu of a rabbit's uterus - 72

5. Cross-section through cervical canal of human uterus 73

6. Section through wall of vagina of monkey (upper part) 75

7. Section through wall of vagina of monkey (lower part) 76

8. Section through mucosa of human uterus, showing pre-menstrual congestion 77

9. Section through mucosa of human uterus, showing extravasation of blood 79

10. Section through mucosa of human uterus, showing sub-epithelial hsema-

tomata - - 81

11. Section through mucosa of human uterus, showing bleeding into the

cavity during menstruation - - 82

12. Section through mucosa of human uterus during the recuperation stage - 83

13. 14. Sections through pnxestrous uterine mucosa of dog - - - 93, 94

15. Section through edge of mucosa of dog during an early stage of recuperation 96

16. Section through portion of mucosa of dog during recuperation period - 97

17. Section through portion of mucosa of dog during late stage of recuperation 98

18. Section through uterine mucosa of bitch forty-eight days after the end of

protestrum (retrogressive stage of pseudo-pregnancy) - 99

19. Section through portion of prooestrous uterine mucosa of rabbit, showing

glandular activity 100

20. Section through uterine mucosa of rabbit nine days after sterile coition - 101

21. Section through uterine mucosa of rabbit twenty-four days after sterile

coition - - 102

22. Section through portion of uterine mucosa of sheep, showing black

pigment formed from extravasated blood - 105

23. Section through ovary of cat - 109

24. Section through ovary of adult dog - 110^

25. Section through ovary of rabbit - 111

26. Section through ovary of pig embryo 112

27. Cortex of pig embryo, showing germinal epithelium, etc. - 113

28. Various stages in the development of the Graafian follicle (rabbit) - 115
29-32. Developing ova from ovary 116, 117

33. Ovary at birth, showing primordial follicles - 1 ] 8

34. Young ob'cyte or egg surrounded by a single layer of f ollicular epithelial cells 121

35. Young human Graafian follicle 122

36. Human ovum at termination of growth period 123

37. Human ovum examined fresh in the liquor folliculi 124

38. Recently ruptured follicle of mouse - - 138

39. Early stage in formation of corpus luteum of mouse 139

40. Late stage in formation of corpus luteum of mouse - - 140

41. Corpus luteum of mouse fully formed 141

42. Discharged follicle of rabbit nineteen hours after coition - 143

43. Section through old corpus luteum - - 148

44. Section through follicle in early stage of degeneration - 150

xiv ILLUSTRATIONS

FIG. 1'AGB

45. Section through follicle in late stage - - 1 .~>2

46. Section through human testis and epididymis . - 160

47. Section through testis of monkey - - 161

48. Section through portion of two seminiferous tubules in testis of rat - 162

49. A cell of Sertoli with which the spermatids are beginning to be connected

(human) - 163

50. Diagram illustrating the cycle of phases in spermatogenesis 164

51. Scheme of spermatogenesis and oogenesis - 165

52. Human spermatozoa on the flat and in profile 167

53. Human spermatozoa 168

54. Different forms of spermatozoa from different species of animals - 169

55. Diagram illustrating wave-like movement of swimming spermatozoon - 171

56. Successive stages in the fertilisation of an ovum of Echinus e*ai/entu#,

showing the entrance of the spermatozoon - 181

57. Three stages in the conjugation of male and female nucleus (Echiim*) 182

58. Fertilisation process in bat's ovum 183

59. Chart showing amounts of oxygen taken up and carbon dioxide given off

after the addition of sperm to the eggs of Echinus 192

60. The insemination of the eggs of Saccocir /•>(••< - 193

61. The entrance of the spermatozoon into the egg of Nereis - 195

62. Passage of convoluted seminiferous tubules into straight tubules, etc. 240

63. Transverse section through the tube of the epididymis 241

64. Transverse section through commencement of vas deferens 242

65. Section through part of human prostate - 247

66. Section through prostate gland of monkey - 249

67. Transverse section through adult human penis 255

68. Section through erectile tissue 256

69. Part of transverse section through penis of monkey 257

70. Distal end of ram's penis, showing glans and filiform appendage 259

71. Transverse section through filiform appendage of ram 259

72. Transverse section through middle of glans penis of ram - 260

73. Distal end of bull's penis, showing glans, etc. 261

74. End-bulb in prostate - - 269

75. Diagram illustrating innervation of genital organs of male cat 271

76. Herdwick ram (normal) 323

77. Herdwick wether (castrated young) - - 323

78. Herdwick wether castrated when four months old - - 324

79. Herdwick wether castrated when five months old - - 324

80. Herdwick ram lamb with one testis removed 324

81. Herdwick wether with epididymes retained - 324
.82. Successive stages in the regression of the comb of the cock after castration 335

83. Ovariotomised brown Leghorn hen - - 342

84. Ovariotomised pullet with plumage and spurs of male - 342

85. Successive stages in the growth of the spurs of a hen after ovariotomy - 343

86. Normal Rouen drake - - 344

87. Normal Rouen duck - - 345

88. Ovariotomised Rouen duck (Type I.) - - 345

89. Ovariotomised Rouen duck (Type II.) 346

90. Transverse section through rabbit's uterus after ovariotomy 349

91. Transverse section through bitch's uterus 9£ months after ovariotomy 349

92. Section through ovary of rat after transplantation on to peritoneum 351

93. Section through ovary of rat after transplantation on to peritoneum 352

94. Transverse section through normal uterus of rat - - - 353

95. Transverse section through uterus of rat after ovariotomy - - 354

96. Transverse section through uterus of rat after ovarian transplantation 355
96A. Section through rat's kidney into the tissue of which an ovary had been

transplanted - - - - - 357

ILLUSTRATIONS N . xv

FIO. PAGE

97. Experimentally produced placenta of pseudo-pregnant rabbit - - 375

98. Part of an early human chorionic villus - 397

99. Early blastocyst of rabbit - ... 495

100. Formation of the amnion in the rabbit - - 413

101. Foetal membranes of horse - - 413

102. Diagram to illustrate the three parts of the wall of the yolk-sac (rabbit) 416

103. Diagram of an opossum embryo and its appendages - 417

104. Diagram showing the arrangement of foetal membranes in Dasyurus - 418

105. Diagram showing the arrangement of foetal mem branes in Peramehs - 419

106. Elongated blastocyst of sheep at thirteenth day of pregnancy - - 420

107. Transverse section through blastocyst of sheep at twenty-fifth day - 421

108. Blastodermic vesicle of rabbit - 422

109. Diagram of blastodermic vesicle of rabbit in longitudinal section - - 423

1 10. Diagram to illustrate foetal membranes of JSrinaceus - 425

111. Hypothetical section of human ovum embedded in decidua - 426

112. Portion of injected chorion of pig - - 427

113. Section through wall of uterus and blastocyst of pig at twentieth day

of pregnancy - 428

114. Diagram representing a stage in the formation of the placenta (pig) - 429

115. Section through uterine and embryonic parts of a cotyledon of sheep

at twentieth day of pregnancy - - 430

116. Section through base of foetal villus, etc. (sheep) - - 431

117. Columnar trophoblast-cells from the base of foetal villus at third month

of pregnancy (cow) to show phagocytosis - 433

118. Histology of the placenta in the cow and sheep - 435

119. First stage of cellular secretion in placenta of cow - 437

120. Ingestion and disintegration of red blood corpuscles by trophoblast of

sheep - 439

121. Absorption of " Stabchen " by trophoblast of sheep - 441

122. The uterine mucosa of dog at about twenty -third day of pregnancy 443

123. Ovum with zonary band of villi - - 445

124. The angioplasmode of dog at thirtieth day of pregnancy - - 446

125. The labyrinth and green border of placenta of dog at fortieth day of

pregnancy - 447

126. Transverse section of a four days' gestation sac of rabbit - - 451

127. Transverse section of a seven days' gestation sac of rabbit - 452

128. Section through uterine mucosa of rabbit pregnant about eighteen days - 453

129. Thickened ectoderm in rabbit, attached to placental lobe - - 454

130. Iron granules in placenta of rabbit at eighteenth day of pregnancy - 459

131. Glycogenic areas of rabbit's placenta at twelfth day of pregnancy - 461

132. Inversion of germinal layers in blastodermic vesicle of mouse - - 468

133. Longitudinal section of implantation cavity of field-mouse about eighth

day of pregnancy - • - 469

134. Longitudinal section of uterus and implantation cavity of guinea-pig - 472

135. Blastodermic vesicle of guinea-pig, showing inversion of germinal layers 473

136. Implantation cavity of guinea-pig - 474

137. Implantation cavity of guinea-pig - - 475

138. Allantoidean diplo-trophoblast of Erinaceu* ~~ - 477

139. Section in situ of ovum of Eriiiaceus - 478

140. The extension of yolk-sac against lacunar trophoblast in Erinaceus 479

141. Transverse section through uterus of Sorex at a stage when the blasto-

cysts are still in the oviducts - - 480

142. Part of the anti-mesometrial wall of the uterus of Sorex - - 482

143. Uterus and embryo of Sorex - 483

144. Orifice of uterine gland of mole with trophoblastic dome - - 485

145. Replacement of omphaloidean by allantoidean placenta - 486

146. Placenta of bat - - - - - - - - 488

xvi ILLUSTRATIONS

no. I>A6E

147. Median longitudinal section of an early human ovum, 0'4 mm. in length 491

148. Diagram of the earliest human ovum hitherto described 494

149. Section through the wall of the uterus in the early part of pregnancy 495

150. Section of a portion of the wall of the human blastocyst - 496

151. Section of a portion of the necrotic zone of the decidua, etc. 497

152. Section through embryonic region of ovum - 498

153. Condition of the glands at the beginning of pregnancy in map 499

154. Median longitudinal section of embryo of 2 mm. 500

155. Diagram of stage in development of human placenta 501

156. Fat in a villus of human placenta - 504

157. Iron granules in a villus of the placenta in man - 506

158. The first stage in the revolution of the equine foetus 568

159. The foal in the normal position for delivery 569

160. Virginal external os (human) 583

161. Parous external os (human) - 583

162. Section of mammary gland of woman 589

163. Section of mammary gland (human) during lactation 590

164. Section of mammary gland (human) in full activity 591

165. Section through an alveolus with fat drops in cells 592

166. Section of developing mammary gland of horse - 606

167. Section of mammary gland (human), showing developing alveoli - 607

168. Photograph of mammary tissue of virgin rabbit - 617

169. Photograph of mammary tissue of pseudo-pregnant rabbit 617

170. Masculinisation of guinea-pig - 696

171. Feminisation of guinea-pig - 697

172. Feminised guinea-pig with large protruding teats and small penis 698

173. Normal male guinea-pig with rudimentary teats and large penis - 698
174-180. Diagrams from Minot;s Problem of Aye, Gro>vth, and Death - 704-710

181. Growth of sheep 711

182. Growth of boys and girls - - 711

183. Section through ovary of woman of fifty-six, showing degeneration of

follicles, etc. - 716

184. Section through uterine mucous membrane of woman of sixty - - 717

185. Section through vaginal mucous membrane of woman of sixty-one - 718

186. Group of nerve-cells from the first cervical ganglion of a child at birth - 719

187. Group of nerve-cells from the first cervical ganglion of a man of

ninety-two - ... 720

188. Land tortoise aged at least eighty-six, belonging to M. Elie Metchnikoff 722

189. Lonk sheep aged eighteen years, with her last lamb - 723

INTRODUCTION

SINCE the time when physiology first became an organised science
many volumes have been written on the digestive, excretory, nervous,
and other systems, but until recently no attempt has been made
to supply those interested in the reproductive processes with a
comprehensive treatise dealing with this branch of knowledge.
Indeed, in many text-books on physiology now commonly in use
either the section devoted to the reproductive organs is restricted to
a few final pages seldom free from error, or else the subject is entirely
omitted. Yet generative physiology forms the basis of gynaecological
science, and must ever bear a close relation to the study of animal
breeding. In writing the present volume, therefore, I have been
actuated by the desire to supply what appeared to me to be a real
deficiency ; and in doing so I have attempted, however inadequately,
to co-ordinate or give a connected account of various groups of
ascertained facts which hitherto had not been brought into relation.
For this purpose I have had occasion to refer to many books and
memoirs dealing with subjects that at first sight might have been
supposed to differ widely. Thus, works on zoology and anatomy,
obstetrics and gynaecology, physiology and agriculture, anthropology
and statistics, have been consulted for such observations and records
as seemed to have a bearing on the problems of reproduction. •

My sources of information are duly acknowledged in the footnotes,
but I am glad to take this opportunity of mentioning the following
works from which I have obtained special help : " The Evolution of
Sex," by Professors Geddes and Thomson ; " Obstetrics," by Professor
Whitridge Williams; the sections on the male and female reproductive
organs, by Professor Nagel and Dr. Sellheim, in Professor Nagel's
" Handbuch der Physiologic des Menschen " ; " Experimental Zoology,"
by Professor T. H. Morgan ; and the writings of Mr. Walter Heape.

The present volume is addressed primarily to the trained biologist,
but it is hoped that it may be of interest also to medical men engaged
in gynaecological practice, as well as to veterinarians and breeders of

2 THF^ PHYSIOLOGY OF REPRODUCTION

animals. As a general rule, I have confined myself to the physiology
of generation among the higher forms, and more particularly the
Mammalia, but I have not hesitated to discuss the reproductive
processes in the Invertebrate in cases where they seemed likely to
elucidate the more complex phenomena displayed by the higher
animals. The all-important questions of heredity and variation,
although intimately connected with the study of reproduction, are
not here touched upon, excepting for the merest reference, since
these subjects have been dealt with in various recent works, and any
attempt to include them would have involved the writing of a far
larger book. Similarly, the subject matter of cytology, as treated in
such works as Professor Wilson's volume on the cell or the recent
works by Professor Agar and the late Professor Doncaster, is also
for the most part excluded.

Tt may be objected that for a book on physiology much space
is devoted to the morphological side of the subject. This has
been done purposely, since it seemed impossible to deal adequately
with the physiological significance of the various sexual processes
without describing the anatomical changes which these processes
involve.

In preparing this work I have been assisted by many friends. I
have been fortunate in securing the co-operation of Dr. William
Cramer and Dr. James Lochhead, of the University of Edinburgh.
Dr. Cramer has contributed the section on the biochemistry of the
sexual organs, while Dr. Lochhead has written the chapters on foetal
nutrition and the metabolism of pregnancy, a labour of no inconsider-
able magnitude in view of the complexity of the subject. I take this
opportunity of recording my indebtedness to Mr. Walter Heape,
through whose influence I was first led to realise the importance of
generative physiology both in its purely scientific and in its practical
aspects. I am under no light obligation to Professor Sir Edward
Sharpey Schafer for valuable and ready help at all stages in the
preparation of this volume. Not only did he look through the original
manuscript of the chapter on " The Testicle and Ovary as Organs of
Internal Secretion," but he gave also much helpful advice and criticism
on various points connected with publication. Indeed, it is not too
much to say that had it not been for him, the book would scarcely
have been written. Sir Hugh K. Anderson, Master of Gonville and
Caius College, and Professor Sutherland Simpson have read the
manuscript or first proofs of the chapter dealing with " The Accessory
Male Organs." The late Mr. E. S. Carmichael, of the Eoyal Infirmary,
Edinburgh, read the section dealing with parturition. Professor J. H.
Ashworth looked through the chapter on " Fertilisation " in the first
edition ; and Professor F. G. Hopkins did the same for Dr. Cramer's

INTRODUCTION 3

biochemical chapter. Sir H. Anderson and Professor Ashworth have
also given me the benefit of their special knowledge in other parts of
the work. To all these I am under obligations. I wish also to tender
my thanks to those authors and publishers who have kindly allowed
me to reproduce illustrations from their respective works, as well as
to record my indebtedness to the following, who have been of service
by giving me information, important references, or assistance in other
ways : — Dr. Nelson Annandale, Superintendent of the Indian Museum,
Calcutta ; Dr. W. Blair Bell, of Liverpool ; Dr. Eagle Clarke, lately
Superintendent of the Scottish National Museum ; Professor J. C.
Ewart, of the University of Edinburgh ; Professor J. P. Hill, of
University College, London ; Dr. A. C. Haddon, of Christ's College ;
Professor W. A. Jolly, of the University of Cape Town ; Dr. Janet E.
Lane-Claypon, of London ; Mr. D. Gr. Lillie, of St. John's College ; Mr.
K. J. J. Mackenzie, of Christ's College ; Mr. F. A. Potts, of Trinity
Hall; Professor C. G. Seligman, of London; and Sir Arthur E.
Shipley, Master of Christ's College. Lastly, I wish to acknowledge
the assistance of Dr. C. H. Crawshaw, of Christ's College, in the
correction of the first proofs, as well as to express my obligations to
Mrs. Kingston Quiggin for the willing labour she expended in
preparing the index and finally revising the text of the first edition,
and to Mr. Richard Muir for the skilful manner in which he
executed those drawings which were new.

CHAPTEK I
THE BREEDING SEASON

" To everything there is a season, and a time to every purpose under the
heaven."— Ecclesiastes iii. 1.

" IT is well known that almost all animals, except man, have a
stated season for the propagation of their species. Thus the female
cat. receives the male in September, January, and May. The she-
wolf and fox in January ; the doe in September and October. The
spring and summer are the seasons appointed for the amours of
birds, and many species of fishes. The immense tribe of insects
have likewise a determinate time for perpetuating their kind ; this
is the fine part of the year, and particularly in autumn and spring.
The last-mentioned class of beings is subject to a variation that is
not observed in the others. Unusual warmth or cold does not retard
or forward the conjunction of birds or quadrupeds; but a late spring
delays the amours of insects, and an early one forwards them. Thus
it is observed that, in the same country, the insects on the mountains
are later than in the plains."

The foregoing quotation from Spallanzani's "Dissertations,"1
although not strictly accurate in all its statements, contains a
clear recognition of two fundamental facts which indeed have
been realised from the earliest times; first, that the periods of
reproductive activity among the great majority of animals (not to
mention plants) occur rhythmically, the rhythm having a close
connection with the changes of the seasons ; and secondly, that the
reproductive rhythm is liable, to a greater or less extent, to be
disturbed or altered by climatic or other environmental influences.
And while there may be a basis of truth for the statement that the
periodicity of the breeding season in the higher animals is less liable
to modification than is the case with certain of the lower forms of
life, there is abundant evidence that among the former no less
than among insects the sexual functions are affected by external
conditions and food supply.

Darwin remarks that any sort of change in the habits of life of

1 Spallanzani, Dissertations relative to the Natural History of Animals and
Vegetables. Translated from the Italian, vol. ii., London, 1784.

THE BREEDING SEASON 5

an animal, provided it be great enough, tends in some way to atfect
the powers of reproduction. " The result depends more on the
constitution of the species than on the nature of the change; for
certain whole groups are affected more than others ; but exceptions
always occur, for some species in the most fertile groups refuse to
breed, and some in the most sterile groups breed freely." " Sufficient
evidence has now been advanced to prove that animals when first
confined are eminently liable to suffer in their reproductive systems.
We feel at first naturally inclined to attribute the result to loss
of health, or at least to loss of vigour ; but this view can hardly be
admitted when we reflect how healthy, long-lived, and vigorous many
animals are under captivity, such as parrots and hawks when used
for hunting, chetahs when used for hunting, and elephants. The
reproductive organs themselves are not diseased; and the diseases,
from which animals in menageries usually perish, are not those which
in any way affect their fertility." 1

It would seem probable that failure to breed among animals in a
strange environment is due not, as has been suggested, to any toxic
influence on the organs of generation, but to the same causes as
those which restrict breeding in a state of nature to certain particular
seasons, and that the sexual instinct can only be called into play in
response to. definite stimuli, the existence of which depends to a large
extent upon appropriate seasonal and climatic changes.2

There are at present no sufficient data for a comparative account
of the physiology of breeding among the lower animals ; and in the
present chapter, which is preliminary in character, I shall content
myself with stating a few general facts about the breeding season,
giving illustrations, taken from various groups of Vertebrates and
Invertebrates, of its seasonal recurrence, and the manner in which
this varies under altered conditions of life.

PROTOZOA

Among the Protozoa the organisms pass through successive phases
of vitality, which are comparable to the different age-periods of the
Metazoa. In such simple forms of life, fission or division into two
parts is the usual method of reproduction,3 and the frequency of
its occurrence appears to depend more upon the phase which has

1 Darwin, Variation of Animals and Plants, Popular Edition, vol. ii.,
London, 1905.

2 See especially page 18, where Bles's observations on the breeding habits
of Amphibia are referred to.

3 In this process no material is lost, and two simple nucleated organisms
result. During the period of maturity referred to in the text, multiplication
is often preceded by union (either temporary or complete) of two individuals,
and this process is called conjugation (see p. 220, Chapter VI.).

6 THE PHYSIOLOGY OF REPRODUCTION

been reached in the life-cycle, than upon the influences of the
environment. Thus, there is a period of extreme vigour of cell-
multiplication, corresponding to the youth of a metazoon ; secondly,
there is a period of maturity, characterised by changes in the
chemical and physical properties of the cell, and leading to the
formation of conjugating individuals ; and finally, in forms which
do not conjugate, there is a period of senescence which ends in
death. It is interesting to note, however, that the rapidity of
fission is affected by the temperature and the food; for example,
an individual of the Ciliate Infusoriau, Stylonychia pustulata, if
well supplied with food, divides once in twenty-four hours in a
temperature of from 5° to 10° (1, and once in twelve hours in a
temperature of from 10° to 15° C.1 In Paramcecium aurelia, too,
it has been found that the rate of reproduction is influenced by
temperature after the manner of a chemical reaction.2 Again,
Flagellate Infusoria of different kinds have been induced to conjugate
by changing the temperature or increasing the density in the
surrounding medium.3 Furthermore, the life-cycle of Paramcecium
may be renewed without the occurrence of conjugation, that is to
say, fission can be made to continue and senescence can be
avoided, by introducing a change in the composition of the medium
surrounding the culture.4 (See p. 222.)

Moreover, there is evidence that in the case of Colpoda steini
at least the occurrence of conjugation is determined entirely by the
conditions of the surrounding medium.

CCELENTERATA

With the majority of the Metazoa, as already indicated, there
is a more or less definitely restricted season to which the occurrence
of the chief reproductive processes is confined.

Thus in the common hydra of Bengal (Hydra wientalis, Annan-
dale), which, like most other Ccelenterates, reproduces by budding
as well as by the sexual method,5 the former process occurs chiefly

1 Sedgwick, Student's Text-Book of Zoology, vol. i., London, 1898.

2 Woodruff and Britsell, "The Temperature Coefficient of the Bate of
Reproduction of Paramcecium aurelia" Amer. Jour, of Physiol., vol. xxix., 1911.

3 Calkins points out that the same experiment is performed by mosquitoes
and other insects on certain parasitic Protozoa, as when a parasite is with-
drawn from the hot environment of the Mammalian blood into the compara-
tively cold region of the mosquito's alimentary tract. ("The Protozoan
Life-Cycle," Biol. Bull, vol. xi., 1906.)

4 Calkins, loc. cit.

6 Asexual reproduction is of very common occurrence among the majority
of the lower animals and plants. It may take the form of simple binary
fission (in unicellular organisms), of spore formation, or of germination or
budding. Sexual reproduction consists essentially of the union of two cells

THE BREEDING SEASON 7

during winter, the buds developing into new individuals. Towards
the beginning of the hot weather budding becomes less active,
and in some individuals ceases altogether, while the same thing
happens during periods of temporary warmth in winter. A rise in
temperature induces a proportion of the individuals present in an
aquarium or pond to develop testes or male reproductive glands;
if the rise is considerable it may cause a few of the remaining
individuals to produce ova. On the other hand, no individual living
in its natural environment has been known to exhibit any sign of
sex after the rise in temperature had become steady. The conditions
most favourable to the production of ova appear to be a period of
comparatively low temperature and abundant nutrition followed by
a sudden but not excessive rise of temperature.1

Some of the marine hydroids show an alternation of generations
which does not appear at first sight to be in any way related to
change in the environment. In such cases the fertilised ovum
develops into a polyp which gives rise to a colony of polyps by a
process of sexual reproduction. After the colony has reached a
certain size, a new kind of bud is formed, and this becomes
a jelly-fish. The latter, after leading an independent existence,
produces eggs, and these in turn become fertilised, giving rise to
a new generation of polyps. Morgan points out that as the polyp
colony goes on increasing in size, its relation to its surroundings
must undergo change, and that, very possibly, it is this change
which determines the development of jelly-fish in place of polyps.
If this interpretation is correct the breeding season among marine
hydroids is controlled by environmental conditions, just as it is
among most other animals.2

and their subsequent division to give rise to the new individual. In the
multicellular organisms (Metazoa and Metaphyta) there are two kinds of con-
jugating cells, or gametes, which are specialised for the purpose. These are
produced by the male and female respectively, and are known as spermatozoa
and ova. Thus, sexual reproduction in the Metazoa is a modification of con-
jugation in the Protozoa. (See Chapter VI.)

1 Annandale, "The Common Hydra of Bengal," Memoirs of the Asiatic
Society of Bengal, vol. i., 1906. Of, Whitney, "The Influence of External
Factors in causing the Development of the Sexual Organs in Hydra mridis"
Arch, f, Entwick.-Mechanik, vol. xxiv., 1907. Whitney says that in Hydra,
viridis an abundance of food following a low temperature causes a suppression
of the formation of testes and ova.

2 Morgan, Experimental Zoology, New York, 1907. Morgan shows that
the same point is illustrated by certain recent experiments of Klebs on
flowering plants. These at first produce only leaves and branches. When
they reach a certain size they produce flowers. Klebs regards the develop-
ment of the flowers as being due to a relation that becomes established
between the plant (when it has reached a certain stage of growth) and the
environment. He shows also that by altering the environment a shoot may
be induced to go on growing vegetatively, when it would ordinarily develop
into a flowering branch. The flowering of the plant, therefore, is not merely
the culmination of its form, as most botanists regard it. For much valuable

8 THE PHYSIOLOGY OF REPRODUCTION

Some interesting observations have been recorded by Ashworth
and Annandale1 about the breeding habits of sea-anemones. The
species Sagartia troglodytes and Actinia meeembryanthemum, which
are very prolific in captivity, have been noticed to breed regularly
in the early spring. Actinia commences to produce young in the
beginning of February, and Sagartia about a month later. As a rule
the young are extruded in the early morning, and one individual
may repeat the process every morning for a number of weeks,
when the breeding season comes to an end. In one season, when
the aquaria were somewhat neglected, the specimens of Sagartia
produced fewer young than usual, and these were not extruded
until the beginning of April. Specimens of Actinia living in the
same aquaria were more prolific, but their breeding season was also
somewhat retarded. In the month of August two anemones of the
species Sagartia troglodytes were brought from Thorshavn in the
Fteroes, and placed in the aquaria. In the following October both
of these produced several young ; while in April of the next year
one of them again gave birth, but only to a single anemone. It
seems probable that in this case the change of temperature or
environment had induced the anemones to breed at an unusual
season ; for it is unlikely that October is the normal period for
reproduction in the Faroe's, as by this time the sea has already
begun to run high, and there would be a great risk of the young
anemones becoming destroyed, being unable to attach themselves.

Ashworth has pointed out2 that in the coral Xenia hicksoni,
which lives in the tropics, there is every evidence that spermatozoa
are discharged over a very considerable period, if not practically
throughout the whole year, whereas in the related form Akyoniuvi
digitatum, of Northern Europe, the period during which the sper-
matozoa are discharged is limited to about a month in the winter.
Ashworth remarks that the difference is probably due to the fact
that Xenia, living on reefs in the shallow waters of tropical seas, is
not subject to great variations in temperature and food-supply, while
with Alcyonium such variations are no doubt considerable. In a
similar way Miss Pratt,3 who has studied the process of oogenesis in
Sarcophytum, Holophytum, and Sclerophytum, concludes that the
sexually mature condition in these tropical genera extends over a

and suggestive information on the factors which control breeding in plants
G. Klebs' work should be consulted. ( Willkurliche Entwickelungsandemngen
bei Pfianzen, 1903.)

1 Ashworth and Annandale, "Observations on some Aged Specimens of
Sagartia troglodytes, and on the Duration of Life in Coelenterates," Proc. Roy.
Soc. Edin., vol. xxv., 1904.

2 Ashworth, "Structure of Xenia hicksoni" Quar. Joiir. Nicr. Science,
vol. xlii.

3 Pratt, " On Some Alcyonidse," Herdman's Ceylon Reports, vol. iii.

THE BREEDING SEASON 9

considerably longer period than in the case of corals inhabiting
temperate waters.

It may also be noted that, whereas in the Ctenophora of the
Mediterranean the breeding season extends throughout the year, in
members of the same class in northern seas it only lasts through the
summer.1 \

NEMERTEA, ETC.

The breeding season and its relation to the environment have '
formed the subject of a careful investigation by Child 2 in the case of
a small Nemertean, Stychostemma asensoriatum, which is found very
abundantly in one of the park lagoons of Chicago. The season
extends from May to November or December, according to the
temperature of the water. Egg-laying can occur freely in the
laboratory, the eggs being deposited always during the night, or in
darkness, vrhen the animals move about freely. Although breeding
in the natural state is restricted to the warmer part of the year, eggs
can be obtained in the laboratory at practically any time, by simply
regulating the temperature. Thus egg-laying can be induced in the
winter at ordinary room-temperature, even though the worms are
kept without food. " In animals which contained only a few small
oocytes when taken, and which are kept in clean water without food,
the growth of the oocytes will continue, and within a week or two
eggs may be laid." " The body of the animal may even decrease
somewhat in size during the growth of the oocytes." It is clear,
therefore, that in Stychostemma the limits of the breeding season are
determined chiefly by the temperature of the water, and that food is
a factor of secondary importance.

Similarly, in the case of the parasitic Trematode, Diplozoon
paradoxum, which ordinarily produces eggs only in the summer, it
has been found that the formation of eggs could be artificially
prolonged throughout the winter, if the fishes on whose gills the
animal lives are kept in an aquarium at summer heat.3

ANNELIDA

Certain species of Polychiet Annelids, known as the Palolo worms,
exhibit a quite remarkable regularity in the periodicity of their
breeding habits. During their immaturity all the Palolos live in
burrows at the bottom of the water. With the attainment of sexual
maturity, and under certain peculiar conditions, they swarm out for

1 Bourne, "The Ctenophora," Treatise on Zoology, vol. ii., London, 1900.

2 Child, "The Habits and Natural History of Stychostemma," American
Naturalist, vol. xxxv., 1901.

3 Semper, Animal Life, London, 1881.

I A

io THE PHYSIOLOGY OF REPRODUCTION

purposes of breeding. In the Atlantic Palolo (Eunice fuc.ata) and
the South Pacific Palolo (Eunice viridis) the process invariably takes
place twice, upon or near the day of the last quarter of the moon
and with the first rays of the sun ; but with the former species it
occurs in June and July, and with the latter in October and November.
The general conditions of existence for these worms would appear to
be remarkably uniform, the temperature variation being from 24° to
30° only. In the Japanese Palolo (Ceratocephale osawai) the swarming
takes place on nights closely following the new and full moons (i.e.
when the spring tides occur), in October and November, the worms
swimming out regularly four times a year. Each swarming-period
lasts from one to four days. It has been noted further that the swarm
is greater after the new moon (when the spring tide is highest) than
after the full moon (when the tide is not so high), that each swarm-
ing takes place invariably just after the flood in the evening, that it
continues for from one to two hours, and is generally larger on warm,
cloudy nights than on clear, chilly nights. It would appear also that
no individual worm takes part in more than one swarming, in the
year.1

ARTHROPODA

Innumerable instances of the periodicity of breeding and its
relation to seasonal and environmental changes might be adduced
from the great group of Arthropods, but the reason for the variations
which occur is not always obvious. Thus, in the common crayfish
(Astacus fluviatilis), in France the males are said to approach the
females in November. December, arid January, whereas in England
they begin to breed as early as the commencement of October,
if not earlier.2 Also, in the Cape species of Peripatus (P. capensis)
birth takes place in a fixed season (during April and May), whereas,
in the South American species, births .are said to occur probably
throughout the entire year.3

In the case of the hemipterous insect known as the plant-louse
(Aphis), we have evidence that the mode of reproduction is dependent
upon temperature. In a favourable summer the females of this

1 Izuka, "Observations on the Japanese Palolo," Jour, of the College of
Science, University of Tokyo, vol. xvii., 1903. This worm is a Phyllodocid and
not a true Palolo. Other swarming Polychsetes are Nereis dumerilii, which
swarms occasionally ; Nereis limbata, in which each sex secretes a substance
which activates the other, the males swarming first and being followed by the
females ; and Odontosyllis enopla (a Bermudan syllid), in which the female is
phosphorescent intermittently at the hind end of the body, her appearance
being followed by the male, the phosphorescence of the female ceasing after
spawning is over. I am indebted to Mr. C. F. A. Pantin, of Christ's College, for
this information.

2 Huxley, The Crayfish, London, 1880.

3 Sedgwick, " Peripatus,''' Comb. Nat. Hist., vol. xii., London, 1901.

THE BREEDING SEASON 11

animal may produce as many as fourteen consecutive generations of
young by parthenogenesis, the ova undergoing development without
being fertilised by the male. At the beginning of the winter male
plant-lice make their appearance and fertilise the eggs, which develop
in the succeeding spring. Reaumur, however, by artificially main-
taining a constant summer temperature, succeeded in producing
more than fifty parthenogenetic generations of plant-lice, all descended
from a single mother.1

Morgan, however, describes some observations which seem to
indicate that the change is not merely due to temperature. He
shows, for example, that the sexual forms of Aphis may appear in
the autumn before the onset of the cold weather, and conversely that
many individuals may continue to reproduce parthenogenetically,
until finally they perish from the cold. Morgan suggests that the
alternation in the mode of reproduction may depend upon changes
which take place in the food-plant in the autumn, instead of being
solely a temperature effect. He shows also that there is evidence for
the conclusion that in the genus Chermes, in which the alternation of
generations occurs between the fir-tree and the larch, the conditions
existing on the larch are those that call forth the sexual forms.2

It has been supposed that the change in the environment is also
responsible for determining the sexes in aphids. Miss Stevens,
however, has recently shown that what appears to be a change in sex
should rather be regarded as a change from the parthenogenetic to
the sexual mode of reproduction.3 According to this view the sex of
each individual is determined by the character of the gamete or
gametes by which it is developed. The supposed influence of food
and external conditions upon sex-determination in various kinds of
insects, and other animals, is discussed at some length in a future
chapter of this work (Chapter XV.).

Semper pointed out long ago that the occurrence of reproduction
(or of the particular mode of reproduction), with insects as with
other animals, depends, among other things, upon the nature of the
diet, upon the chemical conditions of the surrounding medium, upon
the moisture of the air, or upon other circumstances which are
often unknown. Thus, failure to breed in a new environment
is experienced by many Lepidoptera. For example, Death's-Head
hawk moths, which are commonly blown over to this country from
the Continent, but do not breed here continuously, deposit their eggs
on young potato plants, and these develop into moths which emerge
in the autumn. These moths, however, are quite infertile, so that,

1 Semper, loc. cit. 2 Morgan, loc. cit.

3 Stevens, "Studies in the Germ-Cells of Aphids," Carnegie Institution
Report, Washington, 1906.

12 THE PHYSIOLOGY OF REPRODUCTION

as a result, the Death's-Head has never established a permanent
footing in Britain, though stray specimens are often captured.1 In
the case of other insects, such as the mosquito (Anopheles), there is
direct evidence that food is an important factor in egg-formation.
Thus it was found that mosquitoes fed on bananas refused to breed,
but when fed on human blood they invariably laid eggs after two or
three days.2 It is interesting to note also that in the mosquitoes
and other Culicidse, the males are generally unable to suck blood,
this habit being apparently correlated with the function of
oviposition. Among the Empidie, which are carnivorous, the females,
during the nuptial flights, are always fed by the males on small
insects, and they seem incapable of discharging their sexual functions
unless they are fed in this way.3 The Hon. Charles Rothschild, how-
ever, has suggested a more probable explanation of this phenomenon,
namely, that the females would eat the males were they not supplied
by a specific pabulum to divert their attention.4 Hewlett5 has
shown that with the fruit-fly of Pusa (Dacus) sexual attraction is
brought about by an odour emitted by the female and that this can
be imitated artificially by oil of citronella.

In some insects oviposition takes place long after the death of
the males. Thus, Lefroy and Howlett state that in the mango
weevil (Cryptorhyncliiis gravis) the males die in August while the
females live until the following March to lay eggs.6

MOLLUSCA

Among the marine Mollusca, in curious contrast to so many
forms of life, winter is the usual time for the deposition of the eggs.7
On our own coasts Nudibranchs come to shore to lay their eggs from
January to April. Patella spawns from October until the end of the
year. Purpura lapillus is said to be most active during the same
season, but it breeds to some extent throughout the year. Buccinum
undatum breeds from October until May, whereas Littorina breeds
all the year round.8

1 Country Side, October 27, 1906.

2 " Report of Malaria Expedition to Nigeria," Liverpool, Trop. Ned. Memoir,
IV. See also Ross (Nature, vol. Ixxx., 1909), who says that females of Cn.le.i-
and Stegomya apparently only desire to suck blood after fertilisation.

3 Howlett, " Coupling of Empis," Ent. Mag., vol. xliii., 1907.

4 Letter to the author.

6 Howlett, " The Effect of Oil of Citronella on two species of Dacus," Trans.
Ent. ,S'of. Land,, 1912.

6 Lefroy and Howlett, Indian 'Insect Life, Calcutta, 1909.

7 Lo Bianco, " Notizie biologische riguardanti specialmente il periodo di
maturita sessuale degli animali del golfo di Napoli," Mitth. Zool. Stat. Neapol.,
vols. viii. and xiii. Much valuable information concerning the breeding habits
of Mollusca and other animals, inhabiting the Bay, is given in these papers.
See also vols. xviii., xix., and xx. ; and Isset, Biologia Marina, Milan, 1918.

8 Cook, " Mollusca," Camb. Nat. Hist., vol. iii., London, 1895.

THE BREEDING SEASON 13

Among the land-Mollusca there is a more marked periodicity in
the breeding season than among the marine forms. In temperate
climates breeding is restricted to the summer. In the tropics the
occurrence of the breeding season is generally determined by the
alternations of wet and dry seasons. In other cases, where there are
no great seasonal changes, the land-Mollusca may breed all the year
round.1 The snails of the Mediterranean area, according to Semper,
arrive at sexual maturity when they are six months old, and before
they are fully grown. Those individuals which reach this age in the
spring deposit eggs a second time after the heat of the summer is
over, and so experience two breeding seasons in the year, with an
interval of a few months between them during the hot weather.
Semper shows, further, that individuals of the same genera, or
perhaps even of the very same species, in the damper and colder
climates of the north, do not lay eggs till development is complete ;
while in the dry, warm region of the Mediterranean, they have
produced two lots of eggs before they are fully grown. This is
because completion of growth and sexual maturity do not necessarily
coincide. In a similar way, in the pond-snail (I/imncea) the
minimum of temperature which admits of the assimilation of food,
and so of growth, is much above the winter temperature of egg-
deposition.

In tropical climates, where the variation in temperature through-
out the year is reduced to a minimum, the periodicity in the breeding
habits of animals is to a considerable extent obliterated, at least in so
far as it is dependent upon temperature. Semper2 says that few
things impressed him more in the Philippine Islands than the
absence of all true periodicity in the breeding habits not only of the
land-molluscs, but also of the insects and other land-animals. "I
could at all times find eggs, larva;, and propagating individuals, in
winter as well as in summer. It is true that drought occasions a
certain periodicity, which is chiefly perceptible by the reduced
number of individuals in the dry months, and the greater number in
the wet ones ; it would seem that a much smaller number of eggs
are hatched under great drought than when the air is very moist.
Even in January, the coldest and driest month, I found land-snails
which require much moisture, and at every stage of their develop-
ment, but only in shady spots, in woods, or by the banks of streams.
But what was far more striking in these islands was the total
absence of all periodicity in the life of the sea-animals, particularly
the invertebrata ; and among these I could not detect a single species
of which I could not at all seasons find fully grown specimens, young
ones, and freshly deposited eggs." Semper goes on to remark that

1 Semper, loc. cit. 2 Semper, loc. tit.

14 THE PHYSIOLOGY OF REPRODUCTION

even in some cold seas periodicity is far more often eliminated than
is commonly supposed, and mentions that the eggs of the sea-
mollusc, Tergipes, have been found at all seasons, like those of
Littorina on our own coasts. (Cf. p. 29.)

ECHINODERMATA

Sea-urchins and starfish, and other Echinodermata, appear gener-
ally to have a regularly recurrent breeding season, at which the
genital organs swell up to an enormous size. In the sea-urchin,
Echinus esculentus, these organs grow into huge tree-like structures
with branched tubes, lined by the sexual cells. These are sold for
food by the fishermen in Naples, who call them " frutta di mare."
It is said that a single female E. esculentus will produce as many as
20,000,000 eggs in a breeding season. At other times of the year
the generative organs are so reduced as to be scarcely recognisable.
E. esculentus at Port Erin, in the Isle of Man, spawns in June.1 At
Dunbar, in Scotland, it has been observed to spawn at the same
time. The sea-urchins at Naples spawn at the end of the year
(E. acutus being mature in November and December, and E. micro-
tuberculatus from September onwards).2 Fox has written as follows
concerning the Mediterranean and Eed Sea species : —

" The sea-urchins at Suez (Diadema serosum) breed from the
spring until September. During this season the genital products
are developed in cycles correlated with the lunar periods. Sperma-
tozoa and eggs are discharged into the sea between the first and third
quarters of each moon, the majority of individuals spawning about
the time of full moon. The greater number of specimens examined
between the first quarter and full moon have the gonads swollen and
filled with spermatozoa or eggs in a state ready for discharge into the
sea, while a smaller number show that the genital products have
lately been shed. As the third quarter of the moon approaches,
whereas some individuals still have testes or ovaries full of sperma-
tozoa or eggs, most have already spawned. After the third quarter
all have extruded their genital products, and the gonads, now smaller
in size, contain numerous spermatocytes or oocytes in the process of
development into spermatozoa or eggs, to be shed into the sea round
about the next full moon. From the new moon until the first
quarter following it the gonads are filled with spermatocytes or
oocytes in a more advanced stage of development, and, in addition,
there are present in some individuals spermatozoa and unripe or ripe
eggs. After this the same cycle is repeated.

1 Chadwick, Liverpool Marine Biological Committee Memoirs, vol. iii.,
Echinus, Liverpool, 1900.

2 Lo Bianco, loc. cit. The spawning times of most of the Naples Echinoderms
are given in these memoirs.

THE BREEDING SEASON 15

" The gonads of sea-urchins are eaten in different parts of the
world, and the variation in their size, corresponding with the phases
of the moon, is common knowledge in the fish markets of the
Mediterranean and elsewhere. The same fact is referred to by
Aristotle l and other classical writers, both Greek and Eoman." 2

CEPHALOCHORDATA

In the lancelet (Amphioxus lanceolatus) of the Mediterranean
the breeding season extends from spring until autumn, the glands
becoming so large by the ripening of ova and spermatozoa that the
atrium is used up to its utmost capacity. Spawning, when it occurs,
invariably takes place about sun-down (i.e. between 5 and 7 P.M.),
and never, so far as known, at any other times.3

PISCES

Among fishes the duration of the breeding season varies con-
siderably according to the group to which they belong. The ova
of Elasmobramhs are deposited singly or in pairs at varying intervals
throughout a great part of the year. In Teleosts, on the other hand,
the breeding season is limited as a rule to the spring and summer
in temperate climates. In a single individual spawning may last no
longer than a few weeks or even days.4 The enormous number of
eggs produced by most Teleosts must be connected with the absence
of internal fertilisation, involving a large wastage of ova which never
come in contact with male cells or spermatozoa.

The cod, off our own coasts, has a spawning season extending
from January to June, but the majority of individuals spawn in
March. It has been found, however, that in some parts of the
North Sea the cod may spawn in the autumn. In the whiting
the spawning period lasts from early March until the third week
in August.5 The investigations of the Marine Biological Association
have shown that in the plaice of the South Devon bays the maximum
spawning period is between the third week of January and the second
week of February. This period in the North Sea and Irish Sea
would appear to be slightly later. Herdman 6 records that, in the

1 The Works of Aristotle, vol. iv., Historia Animalium, D'Arcy Thompson's
Translation. Oxford, 1910. And see footnote by the translator.

2 MS. by Mr H. Munro Fox, Fellow of Gonville and Caius College, to
whom the author is indebted for this information.

3 Willey, Amphioxus and the Ancestry of the Vertebrates, New York, 1894.

4 Bridge, " Fishes," Camb. Nat. Hist., vol. vii., London, 1905.

5 Masterman, "A Contribution to the Life-Histories of the Cod and
Whiting," Trans. Roy. Soc. Edin., vol. xl., 1900.

6 Herdman, "Spawning of the Plaice," Nature, vol. Ixix., 1904. See also
Wallace (W.), same volume. For information concerning the spawning seasons
of different species of fish, The Journal of the Marine Biological Association, the

i6

year 1904, the plaice in the open-air ponds at the Port Erin
Biological Station started spawning on ord March, and those at
the Peel (Lancashire) Sea Fish Hatchery (under cover) on 1st March.

In the Holostean fish, Lepidosteus, which lives in the fresh waters
of North America, the breeding season recurs with a wonderful
regularity about May. At this time the fish resort in large numbers
to shallower water, where the temperature is higher. Here the ova
and spermatozoa^ are emitted during recurrent periods of sexual
excitement.1 The related fish Amia, of Central and Southern North
America, spawns usually in May, the exact season depending some-
what upon the temperature of the water. The fish make their way
from deep water to the shallow spawning place, which is generally
at the end of a swampy lake.2

In the Crossopterygian fish, Polypterus bichir, the ova ripen in
the summer months from June to September, the breeding season
depending upon the period of inundation, as in most of the Nile
fishes.3 The other species of Polypterus (P. senegalis and P. lapradii),
which inhabit the river-basins of tropical Africa, spawn also in the
wet season in July and August.4

In the Dipnoan, Ccratodus, of Australia the principal time for
spawning is September and October, at the end of the dry season.5
In the other two Dipnoans, Lepidosiren of South America and
Protopterus of Africa, spawning occurs shortly after the emergence
of the fish from their summer sleep. Kerr, writing of the former,
says that the exact time for breeding varies greatly from year to
year in correlation with the extreme variability of the climate, the
swamps, which the mud-fish inhabit, sometimes remaining dry for
prolonged periods.6

Many fishes migrate, before the commencement of the breeding
season, to localities suitable for the deposition of their eggs. Thus,
certain marine fishes like the salmon, the shad, and the sturgeon
ascend rivers for long distances before spawning; others merely
migrate to shallower water nearer shore. The eel, on the other

publications of the English and Scottish Fishery Boards, and the International
Council for Fishery Investigation, should be consulted. These reports show
that the migratory and reproductive periods of fishes are affected by the
temperature, salinity, etc., of the sea.

1 Agassiz, "The Development of Lepidosteus," Proc.'Amer. Acad. Arts and
Science, vol. xiv., 1878.

2 Bashford Dean, "The Early Development of Amia," Qttar. Jour. Alicr.
Science, vol. xxxviii., 1895.

3 Harrington, "The Life-Habits of Polypterus," American Naturalist,
vol. xxxiii., 1899.

4 Budgett, "On the Breeding Habits of some West African Fishes,"
Trans. Zool. Hoc., vol. xvi., 1901.

5 Semon, In the Australian Bush, London, 1899.

6 Kerr, "The External Features in the Development of Lepidosiren
paradoxa," Phil. Trans., B., vol. cxcii., 1900.

THE BREEDING SEASON 17

hand, is a fresh-water fish which migrates to the sea for breeding,
and deposits its eggs in deep water (in spring and early summer).1

Jacobi 2 showed that the migration of the eel is not determined
by the growth of the genital organs, for these do not begin to develop
until the fish have reached the sea. He concluded, therefore, that
eels need salt water before the genital organs can develop. Similarly,
Noel Paton 3 has pointed out that salmon, with their genitalia in all
stages of development, are ascending the rivers throughout the whole
year.

Miescher,4 too, has shown that salmon go practically without food
so long as they are in fresh water, being nourished by the large store
of material which they accumulated while they were in the sea.
This observation has been confirmed by Noel Paton. Miescher and
Paton have shown, further, that the gain in solid material (proteins,
etc.) by the genitalia,5 as the fish pass up the rivers, is met by a loss
in solid material in the muscles. This transference is not brought
about by anything of the nature of a degeneration taking place in
the muscles ; but the latter appear simply to excrete or give out
the material which has been accumulated in them. It should be
noted, however, " that the gain of solids by the genitalia is small as
compared with the loss of solids by the muscle, that in fact the
greater part of the solids lost from the muscles are used up for
some other purpose than the building up of the genitalia." 6 Paton
concludes that the state of nutrition is the main factor determining
migration towards the river, and that, when the salmon has accumu-
lated a sufficiently large store of material, it returns to the rivers
which were its original habitat. It does not seem possible, however,
to maintain that nutrition is a determining influence in the growth
of the genital glands, since these are undeveloped when the fish
begin to migrate and enter upon their period of starvation.

Wiltshire 7 states that in some fishes, at the period of ovi-position,
the lips of the genital orifice swell and become congested. This

1 Schmidt (,T.), "The Breeding Habits of the Eel," Phil. Trans., B.,-vol. ccxi.,
1922.

2 Jacobi,. Die Aalfrage, Berlin, 1880.

3 Paton, Fishery Board Report of Investigations on the Life History of the
Salmon, Glasgow, 1898.

4 Miescher, Histochemische und Physioloqische Arbeiten, vol. ii., Leipzig,
1897.

5 The gain in the genitalia is due largely to the formation of comparatively
simple proteins (protauiines, histones, etc.). See Chapter VIII.

6 Paton, loc. cit. Milroy (" Chemical Changes in the Muscles of the Herring
during Reproductive Activity," Seventh International Congress of Physiolo-
gists, Heidelberg, 1907 ; abstract in Zent. f. Phys.,vo\. xxi., 1907 ; and Biochem.
Jour., vol. iii., 1908) has recently shown that similar changes take place in
the herring, in which, however, the starvation period is briefer.

7 Wiltshire, " The Comparative Physiology of Menstruation," Brit. Med.
Jour., 1883.

IS THE PHYSIOLOGY OF REPRODUCTION

condition he regards as comparable to that which occurs during the
" heat " period of a mammal.

AMPHIBIA

The intimate connection between sexual periodicity and climatic
variation exhibited by many Amphibia and Beptilia, especially in
temperate climates,. was commented on by Spallanzani.1 This close
dependence upon environmental conditions is evidently due largely
to the habits of life of these animals, many of which hibernate or
show great sluggishness in cold weather ; while among Amphibia it
must be associated with the further fact that, whereas most members
of the group live to a great extent upon land, it is necessary for
them to deposit their eggs in water. Spallanzani concludes that
the reason why Amphibia are subject to a variation which is not
observable in birds and Mammals is because the former, like insects,
are cold-blooded, and have a comparatively small supply of internal
heat to animate them when it is cold. " As therefore the exercise
of their functions depends on the heat of the atmosphere, their
amours will also depend upon this cause, and will, of course, be
later in cold than in hot climates, and in both will vary with the
season." .

Spallanzani illustrates the truth of this fact by pointing out that
various species of frogs and toads begin to propagate earlier in Italy
than in Germany or Switzerland.2 On the other hand he records
the observation that the tree-frog and the fetid terrestrial toad were
copulating in the ponds and reservoirs of Geneva in March, at a
time when in Lombardy they had not yet quitted their subterranean
abodes.

It is interesting to note that in the frog and other Amphibia
the ova are produced in winter, when the animals eat little or nothing,
just as the genital organs of the salmon develop during the period
of migration, when the fish have practically ceased to feed.

Bles 3 has discussed at some length the conditions under which
it is possible to induce various species of Amphibia to breed in
captivity. He states that the most necessary condition is that the
animals should be allowed to hibernate at the proper season, and in
order to accomplish this they must be in thoroughly good health

1 Spallanzani, Dissertations, vol. ii., London, 1784.

2 In the common frog (liana temporaria) the usual time for spawning in
Middle Europe is March, earlier in warm, later in cold seasons ; in southern
countries, January or February, but in Norway not until May. Vide Gadow,
Camb. Nat. Hist., vol. viii., London, 1901. This book contains a quantity of
valuable information concerning the breeding habits of many Amphibia and
reptiles.

3^Bles, " The Life-History of Xenopm loevis" Trans. Roy. Soc. Edin., vol. xli.,
1905.

THE BREEDING SEASON 19

when the winter sets in, having passed the summer in the best
circumstances in regard to light, heat, and supply of food. Bles's
observations relate more especially to the African frog, Xenopus
Icevis, but he believes his conclusions to apply in a large degree to
many other species of Amphibia.

The frogs in question were kept in a " tropical aquarium " (that
is to say, an aquarium which could be kept at a tropical temperature
by regulating a heating apparatus). In the summer the temperature
was maintained at about 25° C. ; in December it was allowed to drop
to 15°-16° C. during the day, and 5°-8° C. during the night. The
bottom of the aquarium was covered with earth and stones, on which
the weed Vallisneria, thrived. The water in the aquarium was never
changed. The frogs were fed daily upon small worms, or strips of
liver, until they would eat no more. During winter they became
lethargic, taking very little food. When the temperature rose in
the spring and the days became brighter, the frogs became more
active, especially the males. At this time breeding could be induced
by a certain method of procedure which Bles describes as follows :
" First, the temperature of the aquarium is raised to 22° C. ; and
secondly, when it has become constant, a certain amount of water,
say two gallons, is drawn off morning and evening, allowed to cool
for twelve hours, and then run in slowly in the following manner,
in order to simulate the fall of rain. The cooling vessel is raised
above the level of the aquarium, and a syphon is used to run off the
water. The lower end of the syphon is drawn out to a fine point,
and turned up in such a way that the water rises up like from a
fountain, and falls as spray into the aquarium. . . . By carrying out
such measures I obtained from one female, between April and July
190M, more than fifteen thousand eggs."

The abdomen of the female Xenopus is stated to become very
much distended during the winter by the enormously enlarged

o •/ «/ o

ovaries. "The three flaps surrounding the cloacal aperture are
flaccid until the spring, when they become swollen and turgid, and
more highly vascularised." (Cf. the changes in the female genital
organs of Mammals during the "heat" periods, described in the
next chapters.) The male Xenopus is said to assume its nuptial
characters two days after the temperature is raised to 22° C., and a
very little later it becomes vocal, the voice strengthening from day
to day. Copulation takes place only at night, and spawning may
commence an hour afterwards; but this does not occur unless the
water is changed in the manner above described.

According to Leslie T it would appear that Xenopus, in its native

1 Leslie, " Notes on the Habits and Oviposition of Xenopus l<xvis" Proc.
Zool. Soc., 1890.

20 THE PHYSIOLOGY OF REPRODUCTION

country, breeds only in August, i.e. in the South African spring.
Bles, however, is disposed to think that Xcnopus, like Discoglossus in
the wild state, may breed several times during the spring and
summer, since the frogs in confinement in some years spawned
three times.

Semper1 has shown that if axolotls are kept crowded together
in small aquaria, without plants or seed, individuals which are
sexually mature will not deposit ova even though the water be
changed and abundant food supplied. But if they be suddenly
transferred to aquaria stocked with plants, and with stones and
sand on the bottom and running water, they can be induced to
spawn within a few days, and may do so as often as three or four
times a year. Bles states that 'he is able to confirm Semper's
observations upon axolotls, and that he obtained similar results
by treating individuals of Triton waltlii and of Discoglossus in the
same way.

Annandale2 states that in the Malay Peninsula Eliacophonis
hucomystax and Sana limnockaris appear to breed only after a heavy
fall of rain, and he concludes that the stimulus set up by falling
water is necessary before the sexual impulse can be induced.

Thus there appears to be abundant evidence that breeding in
mature Amphibians does not occur cyclically merely, but it takes
place only in response to certain definite external stimuli. Bles
remarks that if this view is correct, and assuming it to apply to
other groups besides the Amphibia, it helps to explain why many
animals fail to breed in captivity; and also how it is that others
(e.g. insects), in a state of nature, appear in large numbers in one
year and are much less numerous in another.3

It is interesting to note that among frogs and other cold-blooded
Vertebrates there is a periodicity in the occurrence of their reflex
responses.4 It has been shown that if the region of the shoulder-
girdle bearing the four limbs, together with the connected skin and
muscles, and the three upper segments of the spinal cord, are cut out
from the male frog during the breeding season (but not at other
times), the irritation of the skin will cause a reflex, clasping
movement, similar to that characteristic of the normal male at
this period. In spring and early summer, after reviving from their

1 Semper, " Ueber eine Methode Axolotl-Eier jederzeit zu erzeugen," Zool.
Am., vol. i., 1878. See also Animal Life.

2 Annandale, Fasciculi malayenses, Zool., Part I., 1904.

3 See p. 5, Chapter I.

4 The sexual posture of frogs in the act of copulation is maintained as a
spinal reflex. The tortoise is similar. The reflex is inhibited by excitation
of the optical lobes. (Spallanzani, loc. cit. ; Goltz, Ze'it. f. deutsch. med. Wiss.,
1865-66; Tarchanoff, Pfluger's Arch., vol. xl., 1887 ; Albertoni, Arch. Ital. de
Biol., vol. ix., 1887.)

THE BREEDING SEASON 21

winter sleep, frogs tend to be irregular in certain other of their
reflex responses. MacLean has shown that in the heart of the frog,
newt, and salamander, and also the eel, vagus inhibition is absent
or markedly diminished at certain periods corresponding roughly to
the seasons of sexual activity,1 but the significance of the changes
is not very apparent.

KEPTILIA

Reptiles which hibernate usually begin to breed shortly after
the commencement of the warm weather which terminates the
hibernating period, just as in the case of Amphibia. Other reptiles,
which live in warm or tropical climates, also have regularly recur-
rent breeding seasons, in some cases extending over many months,
generally in the spring and summer.2 It would seem that in
reptiles also breeding only occurs in response to certain external
stimuli, and that temperature is the main factor, as supposed by
Spallanzani.

AVES

It would appear almost superfluous to cite examples of sexual
periodicity from among birds. That spring and summer are the
seasons when most birds pair, build their nests, and incubate their
eggs, and that these processes are wont to vary slightly with the
character of the season, are facts that are familiar to all. Bird-
fanciers know also that the capacity of certain birds for egg-laying
may be influenced by diet, and that this capacity can sometimes be
increased (e.g. in the common fowl 3) by the supply of suitable food.
However, in the domestic fowl the production of eggs is mainly
influenced by the season of the year, the maximum production
taking place in the- months of March and April, and the minimum
in October and November. In very high producing strains Pearl
and Surface4 found that there is an additional egg-laying season
in the autumn months. The time of maximum production is
influenced by climatic conditions. Thus Buckley5 found in the
South of England that this occurred in March and April, whereas
in places where the spring is later the maximum is not attained

1 MacLean, "The Action of Muscarin and Pilocarpin on the Heart of
certain Vertebrates, with Observations on Sexual Changes," Biochem. Jour.,
vol. iii., 1908.

2 See Gadow, loc. cit.

3 Wright, The New Book of Poultry, London, 1902.

4 Pearl and Surface, £7.$. Dep. Agric. Bureau, Animal Industry, Bull. 110,
1911.

5 Buckley, Farm Records and the Production of Clean Milk at Monadsmere.

22 THE PHYSIOLOGY OF REPRODUCTION

so soon, and it is well known that the time of greatest production
is earlier if the birds are given shelter.1

With the approach of the breeding season the genital organs
grow enormously until the whole oviduct reaches a state of hyper-
trophic turgescence. Gadow states that in the common fowl the
oviduct at the period of rest is only six or seven inches long and
scarcely a line wide, but that at the time of egg-laying it becomes
more than two feet in length and nearly half an inch in width, thus
increasing the volume about fifty times. This remarkable growth
occurs annually. Gadow remarks also that the testes of the house-
sparrow increase from the size of a mustard-seed to that of a small
cherry, and in so doing temporarily displace the usual arrangement
of the viscera in the body-cavity.2

A very large number of birds seasonally migrate, and this habit,
as in the case of the migratory fish already referred to, is closely
associated with the function of breeding.3 Jenner4 stated long ago
that migration was invariably associated with an increase in size of
the ovaries and testes, and that when these begin to shrink, after
discharging their functions, the birds take their departure. Thus
the ovaries of the cuckoo are stated to be almost atrophied in July.
It would seem quite possible that the annual development of the
sexual organs is the immediate stimulus which, in the individual,
fixes the time for the spring migration, for it is known that in birds
passing northward the ovaries and testes are well developed. (But
cf. fishes, p. 17). Thus wading birds, such as the sanderling shot by
Dr. Eagle Clarke at Spurn Head, in May, were found by him to have
their sexual organs in a very advanced state of growth. These birds
were probably on their way to Greenland or Siberia.

Schafer 5 has suggested that the migratory impulse is determined
by the relation of daylight to darkness, having been brought into

1 Simpson, "An Investigation into the Effects of Seasonal Changes upon
Body Temperature," Proc. Roy. Soc. Edin., vol. xxxii., 1912. That the periodicity
is not simply due to temperature is shown by the Cereopsis goose of Australia
which, when brought to this country, lays its eggs in the autumn and hatches
them in the winter, or at the same time as the Australian summer. Cf. black
swans, see p. 24.

2 Gadow, Article on "Reproductive Organs," in Newton's Dictionary of
Birds, London, 1893-96. Disselhorst also ("Gewichts- und Volumszunahmen
der mannlichen Keimdrusen," Anat. Anz., vol. xxxii., 1908) has called attention
to the enormous increase in size and weight of the testicles and ovaries in
many birds (and also in some Mammals) in the breeding season. • Thus, in
Fringilla, the testicles may increase three-hundredfold.

3 For much of the information given here regarding migration, I am in-
debted to Dr. Eagle Clarke.

4 Jenner, "Some Observations on the Migration of Birds," Phil. Trans.,
Part I., 1824. See also John Hunter, Animal (Economy, London, 1786.

6 Schafer, "On the Incidence of Daylight as a Determining Factor in
Bird Migration," Nature, November 7, 1907.

THE BREEDING SEASON 23

being through the agency of natural selection, in consequence of the
necessity to most birds of daylight for the procuring of food. This
hypothesis explains both the northerly migration in spring and the
southerly migration in autumn, since at both times the birds are
travelling in the direction of increased light (or, if they start before
the equinox, towards regions where they will enjoy longer daylight
later in the season). The suggestion that the time of the spring
migration is determined in each individual by a stimulus set up by
the growing genital organs is in no way opposed to Schafer's theory,
which provides an explanation of the general fact of migration.

It has been noted that the northerly spring migration is far more
hurried than the somewhat leisurely autumn migration in the reverse
direction. Furthermore, although the north-south migratory move-
ments are as a rule extraordinarily regular, it has been observed that
the birds do not all set out together, and that the times of departure
and arrival for each species may vary in any one year by several
weeks. Moreover, golden plover are found migrating across Britain
on their way northward (perhaps to Iceland) at a time when other
individuals of the same species are rearing young in Britain. (The
breeding season in Iceland is about a month or six weeks later than
in Britain.) In view of these facts it is evident that the occurrence
of the migratory movement is dependent not merely upon external
or environmental influences, but also upon internal or individual
ones, and, as already stated, it is not improbable that one of the
factors involved is the state of development of the organs of
generation.

Many birds are double-brooded, having young ones not only in
spring, but also in autumn before the close of the mild weather (in
temperate climates). Swifts are stated to have a second brood in
Southern Europe after leaving Britain in August, and the same is
said to be the case with nightingales. Wiltshire l mentions that a
pair of swifts that stayed behind the others, had a brood in September,
which migrated with the parent birds in October. Whether birds
are single- or double-brooded probably depends to a large extent
upon the duration of the period of incubation. This period in wading
birds and sea-birds is approximately double that of passerine birds ;
but, within the limits of the group to which they belong, it is closely
related to the size of the birds, the size of the egg, and the temperature
of the bird.2 Thus the incubation-period of the stormy petrel is
thirty days ; that of the starling is fifteen or sixteen days ; while
that of the raven (the largest passerine bird) is about nineteen days.
The starling is, as a rule, almost certainly double-brooded, while the

1 Wiltshire, loc. cit.

2 Bergtold, A Study of the Incubation Period of Birds, Denver, 1917.

24 THE PHYSIOLOGY OF REPRODUCTION

petrel and the raven are single-brooded.1 Other birds, such aw the
sparrow, are probably often treble-brooded. It is, of course, well
known that domestication tends to increase the number of broods
which a bird may produce (e.g. in pigeons and poultry). In some
cases, however, domestication has had the opposite effect, e.g. those
breeds of poultry such as the non-sitting breeds which produce large
numbers of eggs but have lost the power of brooding them. Broodi-
ness in fowls is most frequent in spring and summer, the time of
greatest egg-production, and is associated with warmth.2

MAMMALIA

The breeding season in the Mammalia, and the variations in its
periodicity, are discussed at some length in the next chapter. Here
it will suffice to point out that whereas the occurrence of breeding in
any one country or locality is closely connected with the climatic
conditions and the periodicity of the seasons in that country, this
rule does not hold invariably. For while the sheep in South Africa
breeds in April and May (the South African autumn), thus following
the seasons (since sheep breed ordinarily in autumn in this country),
the camels in the Zoological Gardens in London experience rut in
early spring, or at approximately the same time as the breeding
season of the wild camels in Mongolia.3 It has been already noted
that some Mammals refuse to breed in captivity, while in many
others the occurrence of breeding can be regulated to some extent by
such factors as accommodation, heating, and feeding. Also in certain
domestic animals, such as the sheep, the condition of " heat " can be
induced more readily by the supply of additional or special kinds
of food.4

ASSOCIATED PHENOMENA

The approach of the breeding season in many animals, if not in
most, is marked by a display of greater vitality, as manifested by an
increased activity, which relates not merely to the sexual organs but
to the whole metabolism of the body. This enhanced vitality is, as
a rule, maintained throughout the breeding season. Thus male birds
at the time of pairing are in a state of the most perfect development,
and possess an enormous store of superabundant energy. Under the

1 I am indebted to Dr. Eagle Clarke for certain of this information.

2 See Gordon, Jour. Amer. Assoc. Imt., and Invest. Poultry Husbandry,
No. 3, 1915.

3 Heape, "The Sexual Season of Mammals," Qii&r. Jour. Micr. Science,
voL xliv., 1900. The black swans in the Zoological Gardens breed at the
same time as those in Australia. (Cf. also Timor pony, p. 46, and goose, p. 22.)

4 Cf. birds, p. 21, and insects, p. 12. This point is referred to more
fully in Chapter XIV., where the causes which influence fertility are discussed.

THE BREEDING SEASON 25

influence of sexual excitement they perform strange antics or rapid
flights which, as Wallace remarks, probably result as much from an
internal impulse to exertion as from any desire to please their mates.
Such, for example, are the rapid descent of the snipe, the soaring and
singing of the lark, the strange love-antics of the albatross, and the
dances of the cock-of-the-rock, and of many other birds.1 The
migratory impulse, which, as already mentioned, is closely associated
with the periodic growth of the sexual organs, may also very
possibly be regarded as affording evidence of increased vitality at
the approach of the breeding season. Moreover, many of the
secondary sexual characters, both those of the embellishing kind and
others as well, are developed during only a part of the year, which is
generally the period of breeding.

A familiar example of this correspondence between the develop-
ment of secondary sexual characters and the activity of the
reproductive organs is supplied by the growth of the antlers in
stags. At the time of rut, which in the red-deer (Cerints elaphus)
begins in September or October (see p. 44), the antlers, or branched
outgrowths from the frontal bones, are completely developed, having
shed their " velvet " or covering of vascular skin. The animals
during this season are in a state of constant sexual excitement, and
fight one another with their antlers for the possession of the hinds.2
By the end of the year the fighting and excitement have ceased, and
the stags begin once more to herd together peaceably, and apart from
the females. Shortly afterwards the antlers are shed. In most
parts of Britain this occurs about April; but a Highland stag has
been known to drop his antlers as soon after the rutting season as
December, while, on the other hand, some immature animals in the
Lake District are said to carry them until May. After the shedding
of the antlers new ones begin to grow from the pedicles, the growth
taking place chiefly in July and August. When the new antlers
have reached their full development the " velvet " is shed (about the
beginning of September). The size of the antlers, and the number
of branches or " points," go on increasing every year throughout the
reproductive period of the stag's life and until he begins to decline
with old age. 3

In the American prongbuck (Antilocapra americana), which is
unique among hollow-horned ruminants in shedding the horns every
year, the shedding follows the rutting season more closely than in
the stag. The rutting in this species begins in September, and lasts
about six weeks. In old bucks the horns are shed in October, while

1 Wallace (A. R.), Darwinism, London, 1890.

2 The larynx also is said to enlarge at this season, when the stag is wont
to utter a loud bellowing noise.

3 Cunningham (J. T.), Sexual Dimorphism, London, 1900.

26 THE PHYSIOLOGY OF REPRODUCTION

the new growth is not completed until July or August in the
following year.1

A secondary sexual character of a comparable kind occurs in the
male salmon, in which the tip of the lower jaw, during the breeding
season, is turned up and enlarged, as if to protect the fish in fighting
when charged by another male.2

In Polypterus, during the breeding season, the anal fin of the male
becomes greatly enlarged and thickened, and has its surface thrown
into folds between the fin-rays. The object of this modification is
not known.3

The papillre on the hind limbs of the breeding male Lepidosiren
are structures which seem to possess a special significance, since
Kerr4 has shown that they probably serve as accessory organs of
respiration. During the greater part of the year they are relatively
inconspicuous ; but as soon as the animal is set free at the beginning
of the wet season, they begin to grow with remarkable rapidity,
forming slender filaments twyo or three inches in length and blood-
red in colour from their intense vascularity. After the breeding
season is over the filaments commence to atrophy, and eventually
shrink to their former size, but still present for some time a
distinctive appearance owing to their being crowded with black
pigment-cells. Whatever may be the precise purpose of this curious
modification it is certain that its development is associated with
reproductive activity, and so may be regarded as an expression of the
intense vitality which the organism exhibits at this period.

Some animals exhibit in the breeding season a particularly vivid
coloration which is absent from them at other times. The case of
the male dragonet (Callionymus lyra), which becomes1 a brilliant
blue-and-yellow colour, has been discussed at some length by
Cunningham,5 who concludes that the production of the guanin and
pigment that give rise to the colour is to be connected with the
intense nervous excitement which affects the fish at the time of
courtship. " Physiological processes are known to be governed
largely by nervous impulses, and not merely the circulation, but the
excretory activity of the skin, are known to be influenced by
nervous action. Pigment and guanin are produced in the skin by
the secretory or excretory activity of the living cells." 6 Whatever
be the precise explanation of this particular instance of intenser
coloration, there can be no doubt that it is an indication of a more
active metabolism.

1 Cunningham (J. T.), loc. cit.

2 Darwin, Descent of Man, Popular Edition, London, 1901.

3 Budgett, loc. cit. 4 Kerr, loc. cit.

"° Cunningham (J. T,), loc. cit. 6 Cunningham (J. T.), loc. cit.

THE BREEDING SEASON 27

The brilliant colours of the male lump-sucker (Cyclopterus lumpus),
and of other fish l at the time of breeding, are probably due to the
same causes as in the dragonet.2

The tail of the lyre-bird, which is shed at the end of the breeding
season, not to be renewed again in the same form until the following
summer, the brilliant plumage of the breeding drake, the more intense
colouring of the phalarope, and many other birds during the season of
courtship, are familiar instances of the same kind of phenomena.3 The
remarkable plate of horn which is developed in the upper mandible
of the pelican in the breeding season, and bodily shed at the end of
it, and the " gular pouch " in the throat of the breeding bustard, are
examples of a more special kind, the existence of which, however,
must be connected, either directly or indirectly, with the contem-
poraneous increase of sexual activity and the enhanced vitality which
accompanies it.

With birds, however, the assumption of the most perfect male
plumage is not necessarily synchronous with the period of enhanced
vitality. Thus Grinnell * says that in the linnet " the brilliant hue
of the nuptial dress " is acquired in August, or several weeks after
the season of mating, instead of immediately preceding it, and so is

1 Numerous instances are given by Darwin, loc. cit., both for fishes and
Amphibians.

2 The nuptial changes which occur in fishes are not necessarily in the
direction of increased brilliance of coloration. Miss Newbigin describes
these changes in the salmon as follows : " When the fish comes from the
sea the skin is of a bright silvery hue, while the flesh has the familiar strong
pink .colour. The small ovaries are of a yellow-brown colour. As the
reproductive organs develop during the passage up the river, certain definite
colour-changes occur. The skin loses its bright silvery colour, and, more
especially in the male, becomes a ruddy-brown hue. At the same time the
flesh becomes paler and paler, and in the female the rapidly growing ovaries
acquire a fine orange-red colour. The testes in the male remain a creamy
white. After spawning the skin tends, in both sexes, to lose its ruddy
colour and to regain the bright silvery tint ; . the flesh, however, remains pale
until the kelt has revisited the sea" (Report of Scottish Fishery Board, 1898).

Barrett-Hamilton (Proc. Camb. Phil. Soc., vol. x., 1900, and Annals and Mag.
of Nat. Hist., vol. ix., 1902) draws attention to many such sexual phenomena,
and more especially to those occurring in the spawning season in certain
salmonoid fishes of the genus Onchorhynckm. The fish undergo extraordinary
changes in colour and shape, and, since they die when spawning is accomplished,
it is argued that the changes cannot have any aesthetic significance, but
represent a pathological condition in which the fish become continually more
feeble and eventually succumb.

3 Beebe (" Preliminary Report on an Investigation of the Seasonal Changes
of Colour in Birds," Amer. XaL, vol. xlii., 1908) describes an experi-
ment in which certain tanagers and bobolinks, which had been prevented
from breeding, were kept throughout the winter in a darkened chamber
with a somewhat increased food-supply. As a consequence the nuptial
plumage was retained until the spring, when the birds were returned to
normal conditions. They shortly afterwards moulted. The breeding plumage
was then renewed, so that in this case the dull winter plumage was never
acquired.

4 Grinnell, "Concerning Sexual Coloration," Science, vol. xxxiii., (Jan.) 1911.

28 THE PHYSIOLOGY OF REPRODUCTION

not directly associated with excessive sexual vigour. There is only
one moult annually and no pre-nuptial moult, but a progressive
increase in coloration up to and beyond the breeding season.1

In some animals certain glandular organs, apart from those
concerned in the reproductive processes, show a special activity at
the breeding season. For example, in the swiftlets (Collocalia) the
salivary glands become peculiarly active, and secrete a substance
which is allied to mucin, and is employed in building the edible
birds' nests of Chinese epicures.2

A somewhat similar peculiarity exists in the male of the sea-
stickleback (Gusterosteus spinachia), which binds together the weeds
forming its nest by means of a whitish thread, secreted by the
kidneys, and produced only during the breeding season. According
to Mobius, as quoted by Geddes and Thomson,3 the secretion is
semi- pathological in nature, being caused by the mechanical pressure
of the enlarged testes upon the kidneys. The male gets rid of the
thread-like secretion by rubbing itself against objects, and thus, by
an almost mechanical process, the weaving habit is supposed to have
become evolved.

During the breeding season the anal scent-glands of snakes are
said to be actively functional, but not at other times. A similar
fact is stated about the submaxillary glands of crocodiles, and the
cloacal glands of tortoises and other reptiles.4 The secretions of
these glands, like the musk glands of Mammals, no doubt serve the
purpose of enabHng the sexes to detect one another's presence more
easily. (See p. 253.)

PEEIODICITY

The periodicity which is such a marked feature of animal life in
temperate climates has been discussed at some length by Semper.5
This author concludes that the phenomenon in question is dependent
on the severe extremes of summer and winter temperature to which
the animals are exposed. "Every individual requires a certain
duration of life to achieve its individual development from the egg
to sexual maturity and full growth ; the length of time requisite for

1 The assumption of plumage by birds (ducks, bullfinches, etc.) in the
autumn and long before the breeding season may be due to the time of moult.
Patten has shown that in the sanderling there is a pre-nuptial plumage closely
resembling the plumage of the sexually mature bird but preceding the
enlargement of the gonads. (" The Vernal-Plumage Changes in the Adolescent
Blackbird and their Correlation with Sexual Maturity," Brit. Assoc. Report,
1911.)

2 Geddes and Thomson, Evolution of Sex, Revised Edition, London, 1901.

3 Geddes and Thomson, loc. cit.

4 Owen, Anatomy of Vertebrates, vol. i., London, 1866. Lay cock, Nervous
Diseases of Women, London, 1840.

6 Semper, Animal Life, London, 1881.

THE BREEDING SEASON 29

this is very various, and, above all, bears no proportion to the size
attained. . . . This length of time, which we may generally designate
as the period of individual growth, is not alike even for all the
individuals of the same species ; on the contrary, it depends on the
co-operation of so many different factors that it must necessarily
vary considerably. Now, if from any cause the period of individual
growth, say of the salmon, became changed in consequence of the
slower development of the embryo in the egg or of the young larvse,
most or all the young salmon thus affected would die in our climate,
because the greater heat of spring is injurious to them at that stage."
In a similar way it may be argued that the periodicity of the breeding
season, no less than the rate of growth, is governed by the necessities
of the young. No doubt this is true to a large extent, yet at the
same time it is equally evident, as has been shown above in
numerous instances, that this periodicity is greatly affected by
climatic and environmental changes, and even by stimuli of a more
particular nature (cf. frogs, p. 19). But this power, which all
animals in some degree possess, of responding to altered conditions,
may none the less have arisen primarily to meet the requirements
of the next generation ; or, to speak more accurately, that those
animals which breed at a certain particular season (or in response
to certain conditions which prevail at that season) have the advantage
in being able to produce a new generation to which this capacity to
respond similarly will be transmitted. In other words, the restriction
of the breeding habit to certain seasons may have been brought about
under the influence of natural selection to meet the necessities of the
offspring.1

Heape, however, has raised the objection2 that this view is
inapplicable to the Mammalia, in which there is a period of gestation
of greatly varying length in the different species. If the theory were
correct, why, he asks, do some bats experience a breeding season in
the autumn, and not produce young until the following June, although
only two months are required for the development of the embryo in

1 Westermarck (The History of Human Marriage, 5th Edition, London, 1921)
says it is " obvious that the sexual functions are, at least to some extent, affected
by different conditions in different species. This is shown by the fact that
every month or season of the year is the pairing time of one or another species
of Mammals." He goes on to cite examples. Moreover, he points out that
while the Adelie penguin rears its young in the warmest and lightest months,
the giant Emperor penguin does this in the dark season, so that they may be
fostered by their parents until the warm weather, and have the whole summer
in which to change their plumage (Levick, Antarctic Penguins, London, 1914).
Westermarck points out also that where the conditions amid which certain
animals live are fairly uniform throughout the year there is no sexual season.
He instances the whale, the elephant, and the birds of the Galapagos Islands
which are situated very near the equator. (Cf. p. 13.)

2 Heape, "The Sexual Season of Mammals," Quar. Jour. Micr. Science,
vol. xliv., 1900.

30 THE PHYSIOLOGY OF REPRODUCTION

these animals ; why do roe-deer in Germany breed in autumn, while
the embryo does not develop beyond the segmentation stage until
the following spring ; and why does the seal take eleven or twelve
months for gestation when a large dog requires only nine weeks ?
Heape believes that the recurrence of the breeding season is governed
directly by climatic, individual, and maternal influences,1 and that
" variation in the rate of development of the embryo, in the length
of gestation, and in the powers of nursing, are quite sufficient to
provide for the launching of the young at a favourable time of the
year."

I cannot altogether concur in Heape's view of this question.
For it seems to me by no means improbable that whereas the
necessities of the offspring, under changed environmental conditions,
may sometimes have been provided for by modifications in the rate
of development or length of gestation, yet in other cases a similar
result may have been effected by alterations in the season of breeding.
The mere fact that breeding in any one species occurs, as a rule,
periodically at a time which is on the whole well suited to the
requirements of perpetuating the race, is itself presumptive evidence
that the periodicity of the breeding season is controlled (through
natural selection) by the needs of the next generation. Further,
the breeding season having been fixed at one period in the history
of the species, the same season would probably be retained (in the
absence of disturbing factors) by the descendants of that species
under the directive influence of heredity. This view is in no way
opposed to the doctrine that the sexual capacity is developed in the
individual in response to definite stimuli, which are largely environ-
mental and often seasonal.

The occurrence of a succession of "heat" periods within the
limits of a single breeding season no doubt arose in consequence of
the increased opportunity afforded thereby for successful copulation.
The number and frequency of the "heat" periods under these
circumstances are affected by the conditions under which an animal
lives in just the same kind of way as the periodicity of the breeding
season is affected, as will -be shown in the succeeding chapter on the
oestrous cycle in the Mammalia. Concerning the immediate cause of
"heat," and the nature of the mechanism by which it is brought
about, something will be said later (Chapter IX.).

The origin of the breeding season is a wider question. For its
complete solution, as pointed out by Heape, a comparative study of

1 Under the heading of "individual influences" Heape includes special
nervous, vascular, and secretory peculiarities of the individual and its habits
of life. The length of the gestation and lactation periods he calls " maternal
influences."

THE BREEDING SEASON 31

the sexual phenomena in the lower animals is essential, while, as
already remarked, sufficient data for a comprehensive treatment of
this subject do not at present exist.

That the breeding season occurs in some animals " as the result
of a stimulus which may be effected through the alimentary canal is
demonstrated by the effect upon ewes of certain stimulating foods."

"That it is associated with a stimulus which is manifested by
exceptional vigour and exceptional bodily ' condition ' is demonstrated
by the pugnacity of the males at such times, by the restless activity
of the females, by the brilliant colouring of such widely divergent
animals as, for instance, annelids, amphibia, birds, and mammals, by
the condition of the plumage of birds, and of the pelage or skin of
mammals."

" That it is [frequently] associated with nutrition, and that it is
a stimulus gradually collected is indicated by the increased frequency
of the [breeding] season among domesticated mammals as compared
with nearly allied species in .the wild state.

" That it is manifested by hypertrophy and by congestion of the
mucous tissue of the generative organs, and of various other organs,
such as the wattles and combs of birds, the crest of the newt, and by
the activity of special glands, the affection of all of which may be
exceedingly severe, is true.

" These, and many other similar facts, are well known, but they
do not assist in the elucidation of the origin of the function.

" The most they do is to show that the sexual instinct is seasonal,
and that nutrition, whether affected by external or internal factors,
plays an important part in its manifestation." l

The last proposition may be expressed even more generally in the
statement, already formulated, that generative activity in animals
occurs only as a result of definite stimuli, which are partly external
and partly internal ; while the precise nature of the necessary
stimuli varies considerably in the different kinds of animals,
according to the species, and still more according to the group to
which the species belong.2

1 Heape, loc. cit. It should be remembered, however, that many animals,
such as the salmon, have their breeding season after prolonged fasts. See
above. Cf. also the fur-seal, p. 54.

2 For a number of illustrations of periodicity in generative activity among
animals inhabiting the sea-shore, and the tendency to modify chapters of the
normal life-history in accordance with special needs, or in response to peculiar
environmental conditions, see Flattely and Walton, The Biology of the Sea-Shore,
London, 1922.

CHAPTEE II
THE CESTROUS CYCLE IN THE MAMMALIA

" Omne adeo genus in terris hominumque ferarumque
Et genus sequoreum, pecudes, pictaeque volucres
In furias ignemque ruunt : amor omnibus idem."

— VIRGIL, Georg. iii.

\
IN describing the sexual processes of the Mammalia, and the

variations in the periodicity of breeding which occur in the
different groups, I have employed the terminology originally
proposed by Heape,1 and afterwards adopted by me,2 in giving an
account of these phenomena in the sheep and other animals. The
terms used may now be defined.

The term seawal season is used by Heape to designate the
particular time or times of the year at which the sexual organs
exhibit a special activity. It is, in fact, employed in practically
the same sense as that in which the expression " breeding season "
is used in the previous chapter. Heape suggests that it is better
to adopt the latter term to denote " the whole of that consecutive
period during which any male or female mammal is concerned in
the production of the young," since the expression is often used to
include the period of pregnancy or even the period of lactation.
The sexual season is the season during which copulation takes place,
but this only occurs at certain still more restricted times, the
periods of " oestrus " (defined below). The male sexual season, when
there is one, is called the rutting season; but in many species the
male animals are capable of copulating at any time, whereas in the
females this function is restricted to definite periods.

The non-breeding season or period of rest in a female mammal,
when the generative organs are quiescent (at least relatively) and
the uterus is normal and comparatively anremic, and the animal
shows no disposition to seek out a mate, is called by Heape the
Ancestrous period or simply the Ancestrum. This period is generally
considerably prolonged, and in many Mammals occupies the greater

1 Heape, "The Sexual Season,"' Quar. Jour. Nicr. Science, vol. xliv., 1900.

2 Marshall, " The CEstrous Cycle and the Formation of the Corpus Luteum
in the Sheep," Phil. Trans., B., vol. cxcvi., 1903. " The CEstrous Cycle in the
Common Ferret," Quar. Jour. Micr. Science, vol. xlviii., 1904. See also Marshall
and Jolly, "Contributions to the Physiology of Mammalian Reproduction :
Part I. The CEstrous Cycle in the Dog," Phil. Trans., B., vol. cxcviii., 1905.

32

THE CESTROUS CYCLE IN THE MAMMALIA 33

part of the year. Its close marks the beginning of the sexual
season.

The first part of the sexual season is occupied by the Prooestrum.
This period is characterised by marked changes in the generative
organs, the uterus becoming congested, while in the later stages
there is often a flow of blood from the external opening of the
vagina. The prooestrum is the period often referred to by breeders
as the time when an animal is "coming on heat," or "coming in
season."

The next period, (Estiiis, or (Estrum (as it is sometimes called),
" marks, the climax of the process ; it is the special period of desire
in the female ; it is during oestrus, and only at that time, that the
female is willing to receive the male, and fruitful coition rendered
possible in most, if not in all, mammals." 1

The periods of prooestrum and oestrus are commonly referred to
together as the " heat " or " brunst " period, and sometimes as the
period of "rut,"2 and no attempt is then made to distinguish
the time occupied by " coming in season," and the time at which the
female is ready to receive the male. This failure to distinguish
the two periods (prooestrum and oestrus) has led to much confusion,
especially in regard to the nature of the relation between "heat"
in the lower Mammals and menstruation in the human female.
As was first pointed out by Heape, it is the prooestrum and not
the entire "heat" period which is the physiological homologue of
menstruation. This is a point which will be dealt with more fully
in the next chapter of this book.

If conception takes place as a result of coition during oestrus,
this period is followed by gestation ; 3 gestation in its turn, after a
short puerperium or period of recovery, is followed by nursing or
lactation, and the latter is succeeded by another anoestrum at the
close of the breeding season.4

If, on the other hand, conception does not occur during oestrus,
the latter is succeeded, either by a short Metcestrum, during which
the activity of the generative system subsides and the organs
gradually resume the normal condition (cat, rabbit), or by a
period which may be called pseudo-pregnancy, in which the changes

1 Heape, loc. cit.

2 The term " rut " is used by Heape in the case of the male only, the
" rutting season," as stated above, being the male sexual season.

3 There is evidence that "heat" may occur abnormally during gestation.
This phenomenon has been observed in dogs, cows, horses, and other animals
(see p. 46). Coition during pregnancy may result in superf rotation (see p. 154),
and may tend to occur periodically at times corresponding to what would have
been the regular heat periods if the animal had remained non-pregnant.

4 In some animals parturition is followed almost immediately by another
procestrum and oestrus, in spite of lactation.

34 THE PHYSIOLOGY OF REPRODUCTION

occurring in the sexual organs are in a general way similar to those
which take place during true pregnancy but without being so
pronounced (dog).1 The pseudo-pregnant period is then followed
by another anoestrum or period of prolonged rest.

In some animals, such as the rat or the rabbit, the metrestrum
may be succeeded by only a short interval of quiescence. This short
interval, which sometimes lasts for only a few days, is called the
Dicestrum. t This in turn is followed by another prorestrous period,
and so the cycle is repeated until the sexual season is over. Such
a cycle (consisting of a succession of the four periods, procestrum,
oestrus, metcestrum, and dioestrum) is known as the Dioestrous cycle.
The number of dioestrous cycles in one sexual season depends upon
the occurrence or non-occurrence of successful coition during oestrus.
Thus, if conception takes place during the first cestrous period of
the season, there can be no repetition of the cycle, at any rate until
after parturition. The cycle may then be repeated. If conception
does not occur at any oestrus during the sexual season, the final
metcestrous period is succeeded by a prolonged ancestrous or non-
breeding period. This is eventually followed by another prooestrum,
marking the commencement of a new sexual season. The complete
cycle of events is called the (Estrous cycle.

The number of dicestrous cycles which can occur in a female
mammal in the absence of the male, or in the absence of successful
coition, depends upon specific and individual differences. Thus in
some animals, such as the Scotch blackfaced sheep in the Highlands,
this number is usually limited to two. In many Eodents, on the
other hand, there may be six or seven, or even more recurrences of
the cycle within the limits of a single sexual season.

Animals in which the oestrus does not recur during the sexual
season, Heape has called Monoestrous animals. Those in which
there' is a recurrence of the dioestrous cycle during a single season,
have been designated Polycestrous animals. The polycestrous condition
may be regarded as a device (using teleological language) to increase
the reproductive powers by providing more frequent opportunities
for successful coition. But as to what factors are actually involved
in bringing about the rhythmic recurrence of the cycle is a question
which must at present be left open. (Of. p. 387.)

The differences in sexual periodicity in both moncestrous and
polycestrous Mammals, the differences in the duration of the sexual
season in polyoestrous Mammals, the great variation which occurs
even in closely allied forms or even within the limits of a single

1 Marshall and Hainan, "On the Post-CEstrous Changes occurring in the
Generative Organs and Mammary Glands of the Non-Pregnant Dog," Proc. Rot/.
Soc.i B., vol. Ixxxix., 1917.

THE CESTROUS CYCLE IN THE MAMMALIA 35

species, and the effects of domestication and climate upon sexual and
reproductive capacity are points which will be considered in describing
the various types of breeding phenomena which exist in the different
groups.

As Heape says, " the complication into which an otherwise simple
story is thrown is due ... to variation in the quiescent period."
The two varieties of the quiescent period (anoestrum and dioestrum)
" are homologous, the one is a modification of the other " ; and the
modification is no doubt related to an increased or decreased power
of reproduction. At the same time, for the purposes of the present
chapter, " the difference between them [must be regarded as] essential,
for their relation to the sexual season renders it necessary to dis-
criminate clearly between them."

MONOTREMATA

Little is known concerning the breeding habits of the platypus
and the echidna, which represent this order, the lowest of the
Mammalia. Semon l states that they breed only once a year, and
that in Echidna, as a general rule, only a single egg is impregnated
and developed at a time. After the egg is laid (for Monotremes, as
is well known, differ from all other Mammals in being oviparous) the
mother stows it away in her pouch. This is always well developed
at the sexual season, after which it disappears, not to appear again
until the approach of the next sexual season. Semon states that,
although the pouch is first visible in the embryo, it is thereafter lost
to sight until the beginning of the first procestrum.

MARSUPIALIA

It would appear probable that most Marsupials breed once
annually, but some are said to do so more frequently. Semon 2 says
that in the native Australian " bear " (Phascolarctus cinerevs), on the
Burnett, the sexual season begins at the end of October. Since he
failed to find pregnant females until the middle or end of November,
it would seem that the sexual season probably extends for three or
four weeks. The males at this time experience a rutting season,
during which they cry loudly, more frequently in the evening
and night, but also during the day. The gestation, as in all

1 Semon, In the Australian Bush, English Edition, London, 1899. See
also Sixta, "Wie junge Ornithorhynchi die Milch ihrer Mutter saugen,"
Zool. Am., vol. xxii., 1899; and Caldwell, "The Embryology of Montremata
and Marsupialia," Phil. Trans., B., vol. clxxviii.

2 Semon, loc. cit.

36 THE PHYSIOLOGY OF REPRODUCTION

Marsupials, is extremely short, the young being transferred at a very
early stage of development to the mother's pouch, as in the case of
Echidna.1

The kangaroos in the Zoological Society's Gardens in London are
stated to display sexual excitement in September, and also in April.
At such times a slight flow of mucus, which may be tinged with a
little blood, has been observed passing from the aperture of the
vagina.2 It would appear, therefore, that kangaroos may breed twice
a year. Unfortunately, there is no positive information available as
to whether oastrus recurs during the same sexual season (see below).

The Marsupial cat (Dcuyurus viverrinus) is monosstrous and has
one breeding season a year, which begins in May or early June and
extends over the winter in Australia, until the first fortnight in
August.3 The procestrurn lasts from four to twelve days, and during
this time the lips of the cloaca become swollen, and the pouch enlarges
slightly and becomes tumid and moist. There are corresponding
internal changes (see below, p. 106). (Estrus lasts for one or two days.
Pregnancy is stated to last not less than eight and not more than
fourteen days. In its absence pseudo-pregnancy occurs, and is
accompanied by a series of changes in the reproductive organs and
mammary glands essentially similar to those taking place in gestation.
The pouch enlarges and the sebaceous, sweat, and mammary glands
also hypertrophy as well as the internal organs (see p. 616). At the
end of the period the animal has been seen to clean out its pouch for
the reception of young, showing that the developmental and cyclical
changes of the sexual organs may extend even to the instincts
associated with parturition and the nursing of the young, although
true pregnancy had not taken place (qf. rabbit, p. 576). The anosstrum
in Dasyurm lasts more than half the year.

Hill states that the opossum (Diddphys aurita) has two breeding
seasons ; one in June to July, and the other at the end of October.
The Virginian opossum, on the other hand, has only one sexual season
and one oestrus. Trichosurus vulpecula and Macropus rnficoUis
breed twice a year, the former in April and September, the latter in
August to September and December to February.4

*

1 In the bandicoot (Perameles) the young are nourished by an allantoic
placenta similar to that of the higher Mammals (see p. 419). This is exceptional
among Marsupials.

2 Wiltshire, "The Comparative Physiology of Menstruation," Brit. JAW.
Jour., 1883.

3 Hill and O'Donoghue, "The Reproductive Cycle in the Marsupial
Da*ywnu viverrinus" tyuar. Jour. Micr. Science, vol. lix., 1913.

4 Hill, " Some Observations on the Early Development of Didelphys aurita "
(Contributions to the Embryology of the Marsupialia, V.), Quar. Jour. Micr.
Science, vol. Ixiii., 1918. See also below, p. 106.

THE CESTROUS CYCLE IN THE MAMMALIA 37

KODENTIA

There can be little doubt that the great majority of Kodents are
polyoestrous. Most of them, so far as is known, have one annual
breeding season, which may, under favourable conditions, extend
over several months. Thus the rat (Mus decumanus) and mouse
(M. musculus) are known to experience a recurrence of the dioestrous
cycle in the absence of the male, while, if pregnancy occurs, a new
" heat " period very rapidly succeeds parturition. In a state of semi-
domestication M. rattus and M. decumanus have, in my experience,
a fairly regular breeding season from about the end of January until
the end of May. During this period the majority of mature females
are either pregnant or suckling their young (that is, of course, among
females which have been allowed to run freely with males).
Pregnancy may occur at other times of the year, but is not nearly so
common. The duration of the dioestrous cycle in the rat is said to
be about five days,1 but observers seem to differ, some stating it to
be longer ; the period of gestation is approximately three weeks.
Heape states that M. minutus and M. sylvaticus are also probably
polycestrous. The bank vole (Arvicola glareolus) is almost certainly
polyoestrous, since it can become pregnant immediately after
parturition at certain times of the year. The same condition no
doubt exists in the field vole (A. agrestis), which breeds in Britain
from January to October.2 According to Lataste,3 Eliomys qucrcinus,
Gerbillus hertipes, Dipodillus campestris, D. simoni, Mcriones shaivi,
and M. longifrons are also polyoastrous. The length of the dicestrous
cycle in all these animals, as observed by the same investigator, is
usually about ten days.

In the wild condition in Britain, according to Heape, recurrent
dioestrous cycles last " about three months, probably, in Arvicola,
agrestis ; from four to six months, probably, in Mus minutus ; about
nine months in Mus rattus ; and even longer, perhaps, in Mus
musculus and M. decumanus." From my own experience with the
two species of rats in captivity, I am disposed to believe that Heape
has overstated the duration of the sexual season in these animals
in a state of nature.

The breeding season in the wild rabbit (Lepus cuniculus) in this
country generally lasts from about February to May, but may be
continued for longer. In the domesticated breeds it sometimes lasts
nearly the whole year if the circumstances be favourable in regard
to warmth and food supply. Heape says that five or six months

1 Long and Evans, "The (Estrous Cycle in the Rat," Anat. Rec., vol. xviii.,
1920.

2 Millais, British Mammals, vol. ii., London, 1905.

3 Lataste, Recherches de Zooe'thique sur les Mammiferes de Vordre des Rongeurs,
Bordeaux, 1887.

38 THE PHYSIOLOGY OF REPRODUCTION

only is the usual duration of the period during which dicestrous
cycles recur in the domestic rabbit, and that if oestrus is experienced
in winter it may occur independently of the possibility of pregnancy,

The duration of the dioestrous cycle varies considerably. "While
some individuals exhibit oestrus every three weeks fairly regularly,
others do so every ten days ; on the whole, I think ten to fifteen
days is the usual length of their dioestrous cycle."1 In Lcj>t'*
variabilis recurrent dioestrous cycles are probably continued for
about two months.2

The squirrel (Sciurus vulgaris) in Britain, according to Heape,
is probably moncestrous ; but this animal, in Southern Europe and
Algiers, according to Lataste, is apparently polycestrous. In Britain
squirrels breed early in the year, and sometimes have a second litter
in August.

It is difficult to determine the length of the procestrum and
oestrus in Rodents, since the external changes which characterise
these conditions are comparatively slight. Heape says that the
procestruiu in the rabbit lasts, probably, from one to four days. At
this time the vulva tends to become swollen and purple in colour,
but there is no external bleeding. According to Long and Evans 3
the cycle is marked by characteristic changes in the cellular and
fluid content of the vagina. Lataste 4 states that external bleeding
occurs during the " heat " periods of Pachyuromys duprasi, Dipodillus
simoni, and Meriones shawi.

The guinea-pig (Cavia porcellus) in captivity can become pregnant
at any season, but more frequently in the summer than in the winter.
Stockard and Papanicolaou 5 state that oestrus occurs every sixteen
days and that the vagina just before these periods becomes filled
with mucus. During the dioestrum there is very little fluid to be
found in the vagina.

Loeb 6 had previously found that the dioestrous cycle lasted from
twenty to twenty-five days, or in animals prevented from copulating,
from fifteen to nineteen days. " Heat " rapidly succeeds parturition,
as in the case of so many other Rodents.7 The period of gestation is

1 Heape, loc. cit.

2 The dioestrous cycles may be interrupted by a period of pseudo-pregnancy
initiated by a sterile coition. See below, p. 101.

3 Long and Evans, loc. cit.

4 Lataste, loc. cit.

\ Stockard and Papanicolaou, " The Existence of a Typical (Estrous Cycle in
the Guinea-Pig," Amer. Jour. Anat., vol. xxii., 1917.

6 Loeb, "The Cycle Changes in the Ovary of the Guinea-Pig," Jour, of
Morph., vol. xxii., 1911. "The Correlation between the Cyclic Changes in the
Uterus and the Ovaries," Biol. Bull., vol. xxvii., 1914.

7 Sobotta, " tiber die Bildung des Corpus Luteum beim Meerechweinchen,"
Anat. ffefte, vol. xxxii., 1906.

THE CESTROUS CYCLE IN THE MAMMALIA 39

about sixty-two days, an unusually long time for so small an animal,
being more than twice as long as the gestation period of the rabbit.
As a result the newly-born guinea-pig is well advanced in develop-
ment, and able to feed for itself, instead of being dependent on its
mother's milk.

In most male Kodents the testes undergo a periodic increase in
size and descend into the sessile scrotum at the beginning of the
season of rut, after which they become smaller again, and are with-
drawn into the peritoneal cavity. In the Leporidse, however, and
in some other species, the testes are not so retracted, but remain
throughout the year in the scrotal sacs.1

UNGULATA

This order contains several examples of animals which are almost
certainly monoestrous in a state of nature, but are polycestrous in
captivity or under domestication. In the latter case the increase
in sexual capacity appears to be due partly to the inherited effects
of domestication, and partly to the direct influence of a more
favourable environment.

For example, the sheep presents a complete gradation from the
apparently monoestrous condition of some wild species to the extreme
degree of -polycestrum, which is reached by certain of the more
domesticated breeds.2

The Barbary wild sheep (Ovis tragelaphus) in the Zoological
Society's Gardens is monoestrous, breeding only once annually.3
The same is stated to be the case with the Burrhel sheep (0. burrhel),
although the moufflon (0. musimoii) in captivity may experience two
or more recurrent dicestrous cycles in an annual sexual season.4 It
would seem, however, from the account given by Lydekker5 of the
breeding habits of 0. musimon, as well as 0. vignei, 0. ammon, and
0. canadensis, that these sheep in their wild condition are probably
moncestrous, for their annual sexual season is of short duration, and
occurs with great regularity. Similarly it may be inferred from
Prjewalsky's statements0 that 0. poli, 0. burrhel, and 0. argali are
monoestrous and breed once a year. Among wild sheep generally
the sexual season occurs as a rule in autumn, but it may vary with

1 Owen, On the Anatomy of Vertebrates, vol. iii., London, 1868.

2 Marshall, "The (Estrous Cycle, etc., in the Sheep," Phil. Trans., B.,
vol. cxcvi., 1903.

3 Heape, loc. cit.

* I am indebted to Mr. F. E. Beddard, Prosector of the Zoological Society,
for this information.

5 Lydekker, Wild Oxen, Sheep, and Goats of All Lands, London, 1898.

6 Prjewalsky, Mongolia, the Tangut Country, and the Solitudes of Northern
Tibet (Morgan's Translation), London, 1876.

40 THE PHYSIOLOGY OF REPRODUCTION

the locality or climate. Thus with 0. vignei in the Punjab, the sheep
begin to breed in September, whereas, with the same species in Astor,
the sexual season must be considerably later, since the young in the
latter district are produced about the beginning of June.1

Scotch Blackfaced sheep in the Highlands experience two
dkestrous cycles, each of three weeks' duration, so that the annual
sexual season for these animals lasts six weeks. In the Lowlands
the sheep of this breed may have at least three recurrent dioostrous
cycles in the absence of the ram, while flockmasters inform me
that, under unusually favourable conditions, there may be as
many as five or six, the duration of each cycle varying from
about thirteen to eighteen days. It can hardly be doubted that
of the two conditions of the Scotch Blackfaced sheep that of the
Highland ewes is the more natural, for sheep, in their wild state, are
essentially mountain animals, being almost entirely confined to
mountain districts in the Holarctic region, their range only just
extending across the border into the far warmer Oriental region.
"The immense mountain ranges of Central Asia, the Pamir, and
Thian-Shan of Turkestan may be looked upon as the centre of
their habitat." 2

The sexual season in hill sheep in Great Britain is ordinarily
from about the middle of November until the end of the year.
Under exceptional circumstances individuals may experience oestrus
at other seasons, such as in April after an early abortion in the
winter. In other British breeds the sexual season is earlier. Thus
Hampshire Down sheep are often " tupped " in the summer, but
they do not, as a rule, breed more than once a year. The Limestone
sheep of Westmorland and Derbyshire, and the Dorset Horn sheep
of the South of England, are the only British sheep which are
ordinarily capable of breeding more than once annually. With the
former the general lambing season is from the middle of February to
the middle of March, but lambs are often born earlier. The ewes
sometimes receive the ram very early when suckling the lambs, so
that a second crop of lambs is born in August. This increase in the
sexual capacity is especially noteworthy in view of the fact that
Limestone sheep are classed as a mountain breed which thrives best
on dry heaths or bare hill pastures. In Dorset Horn sheep lambs
are frequently produced twice a year, but the practice is discouraged
as it is said to deteriorate the ewes. With this breed restrus may
continue to recur (in the absence of the ram) from the summer
sexual season (when the sheep are tupped) onwards until the late
autumn or even longer.

1 Lydekker, loc. cit.

2 Flower and Lydekker, Mammals Living and Extinct, London, 1891.

THE CESTROUS CYCLE IN THE MAMMALIA 41

With many foreign breeds lambs are born twice yearly. Thus
Dr. Annandale informs me that the horned sheep which run half
wild in Patani, in the Malay Peninsula, normally have lambs twice
a year. It would appear also that among the indigenous sheep of
India, which are scarcely ever supplied with any artificial or other
food, green or dry, beyond what they can pick up at the pasture
ground, lambs may be born three times in two years, and that there
are no definite seasons for lambing.1

Among the Merino sheep in Cape Colony the sexual season is
April (the autumn month, corresponding to October in this country),
but some sheep come " in season " earlier. At high altitudes,
however, where the sheep subsist entirely upon the natural produce
of the veldt, the sexual season is May, or a month later than the
usual time in Cape Colony. On the other hand, in the low country
below the second range of mountains, there are two seasons for
" tupping," and lambs are produced twice a year. Among the
Merinos in Argentina there are also two breeding seasons within the
year.

Probably the maximum amount of sexual activity experienced by
any sheep is that reached by certain Australian Merinos which are
described as being able to breed all the year round, a fact which
implies, in the absence of gestation, an unbroken series of dioestrous
cycles. The report of the Chief Inspector of Stock for New South
Wales divides the time of lambing into six periods which embrace
the entire year.2

That the great variability in sexual activity which, the sheep
exhibits is dependent largely upon differences in food supply and
climate cannot be doubted, for the Blackfaced sheep in Scotland
and the Merinos in Cape Colony afford direct evidence that this is
the case. Indeed, the effect of the environment on the recurrence of
breeding was noted long ago by Aristotle,3 who observes that " in
some places where the weather is warm and fine, and food is
abundant," sheep may have lambs twice a year. The result of
flushing (or the practice of stimulating the generative system by
supplying extra food or better pasture, and thereby hastening the
approach of the sexual season and increasing the fertility) is further
evidence of the effect of good nourishment upon the sexual and
reproductive powers. On the other hand, there can be no question
that the varying degrees of breeding activity are in part racial

1 Shortt, .1 Manual of Indian Cattle and Sheep, 3rd Edition, Madras, 1889.

2 Wallace (K.), Farming Industries of Cape Colony, London, 1876 ; The Rural
Economy and Agriculture of Australia and New Zealand, London, 1891 ;
Argentine Shows and Live Stock, Edinburgh, 1904.

3 Aristotle, History of Animals (Cresswell's Translation), Bonn's Library,
London, 1862. Oxford Edition (Thompson's), 1910.

42 THE PHYSIOLOGY OF REPRODUCTION

characteristics, as is shown, for example, by the Dorset Horn sheep
in the South of England, and still more evidently by the Limestone
sheep of Westmorland and Derbyshire. But that an increase in the
duration (or more frequent recurrence) of the sexual season is not
necessarily a highly artificial condition or the result of special
attention in regard to food supply, etc., on the part of the flock-
master, is shown by such a condition occurring among the indigenous
sheep of India and the half-wild sheep of Patani.

The duration of the dioestrous cycle in Blackfaced sheep, as
already mentioned, is from about thirteen to twenty-one days, the
variation appearing to depend partly upon the nature of the country
in which they live. In other breeds the cycle may be said to vary
within approximately the same limits. Ellenberger,1 however, gives
from twenty to thirty days as the length of this interval. The
procestrum and oestrus together do not as a rule occupy more than
two or three days, and oestrus alone may last for only a few hours.
The external signs of the prorestrum are comparatively slight in
sheep.2 The vulva is usually somewhat congested, and there is often
a flow of mucus from the external generative aperture, but blood is
seldom seen. Owing to the extreme shortness of the "heat" period
the mucous flow may continue during the oestrous and metoestrous
periods. The internal changes are briefly described in the succeeding
chapter. The only external indication of oestrus is that afforded by
the behaviour of the ewes. At this time they tend to follow the ram,
and display a general restlessness of demeanour. The period of
gestation is twenty-one or twenty-two weeks. Nathusius' observa-
tions show that it is fairly constant within the limits of particular
breeds.3

The oestrous cycle in the sheep, and its great variability, have
been discussed at some length, since this animal is probably typical
of most Ungulata in the way in which its generative system is
affected by different conditions of life, while the facts about other
Ungulates are not so perfectly known. The effect of changed
conditions upon the sheep's fertility, i.e. upon its capacity to bear

1 Ellenberger, Verqleichende Physiologic der Hamsaiiqethiere, vol. ii., Berlin,
1892.

2 It is interesting to note that Aristotle clearly distinguished between
the prooestrum and oestrus in the sheep and goat. This is what he says :
" With ewes and she-goats there are signs of menstruation in breeding time,
just before the time for submitting to the male ; after copulation also the signs
are manifest, and then cease for an interval until the period of parturition
arrives" (Thompson's Translation, loc. cit.). 'The "signs after copulation" doubt-
less refers to vaginal bleeding, such as has been observed by Mr. Hammond
in cows at such a time.

3 Nathusius, " Ueber einen auffallenden Racemmterschied in der Trachtig-
keitsdauer der Schafe," Zool. Garten, Jahrg. 3, 1862. (Cf. p. 68.)

THE CESTROUS CYCLE IN THE MAMMALIA 43

young (as distinguished from mere sexual capacity), is a subject
which is dealt with more fully in a future chapter (Chapter XIV.).

The wild goat, like the wild sheep, has a very restricted sexual
season,1 while, according to Low, the domesticated goat experiences
oastrus at very frequent periods.2

A similar statement may be made about cattle, for Heape 3 says
that whereas wild cattle in captivity are capable of reproduction at
any time of the year, and experience a remarkable increase in the
recurrence of their dioastrous cycles, we are led to infer from the
limited calving season among similar animals in the wild state that
the sexual periods are likewise restricted. Raciborsky4 says that in
the more domestic types of cattle the cows receive the bull more
frequently than in the wilder breeds. Ellen berger5 states that
among domestic cattle the dioestrous cycle varies from about two to
four weeks, but Schmidt0 has shown that the differences may lie
much greater. Wallace 7 says that oastrus recurs in summer every
nineteenth day, but in winter it may not recur oftener than every
twentieth or every twenty-first day. Usually the cow seeks the bull
again four or five weeks after calving. Shortt,8 however, states that
in India this does not occur until after six or nine months. Blood
is not infrequent in the external discharge of cows and heifers, but
such discharge does not usually appear until after oestrus is over.
Emrys-Roberts9 has described the internal generative organs of a
procestrous cow as containing a watery secretion tinged with blood.
The secretion was found to contain far less mucin than during the
anoastrous period.10

The period of gestation in cattle is about nine months, but it is
slightly variable.

According to Heape, who has collected evidence from various
authorities, the ibex, rnarkhor, barasingha, and HemMragw jerulaicus
in Cashmir, as well as the American bison, black-tailed deer in
Montana, red-deer, fallow-deer, and roe-deer,11 and several antelopes

I Lydekker, loc. cit.

a Low, The Domesticated Animals, London, 1845.

3 Heape, loc. cit.

4 Raciborsky, Traite de Menstruation, Paris.

6 Ellenberger, loc. cit.

•6 Schmidt, " Beitrage zur Physiologie der Brunst beim Biude," Dissertation,
Zurich, Munchen, 1902.

7 Wallace (R.), loc. cit.

8 Shortt, J Manual of Indian Cattle and Sheep, 3rd Edition, Madras, 1889.

9 Emrys-Roberts, "A Further Note on the Nutrition of the Early Embryo,
etc.," Proc. Roy. Soc., B., vol. Ixxx., 1908.

10 According to Emrys-Roberts, the profuse mucinous secretion during the
prooestrum in the Mammalia is derived, not from the body of the uterus, but
from the cervix and vagina.

II There has been some controversy regarding the breeding season and
peiiod of gestation in roe-deer. According to Bischoff (Entwicklungsgeschichte

44 THE PHYSIOLOGY OF REPRODUCTION

are all probably monoestrous in the wild state. This is rendered not
unlikely from the limited sexual and calving seasons which these
animals are known to experience, but it is by no means certain.
" The American bison experiences a sexual season from some time
in July until some time in August. [Catlin says August and
September are the months when they breed; see below.] In the
Cashmir ibex it persists during parts of November and December.
In the markhor and Hemitragus jerulaicus in Cashmir it occurs in
December, while in the barasingha in that country, from 20th
September to 20th November, it has been observed. ... In Scotland
the red-deer's sexual season lasts three weeks, during September and
October, according to Cameron;1 while in this country [England]
September is the sexual month for the fallow-deer,2 and July and
August the time when the roe-deer will receive the male.

" In all these cases there can be little over three weeks during
which copulation takes place, and the extremely limited period
during which parturition occurs strongly corroborates the view
that this is the extent of the usual time during which sexual
intercoiirse is possible. The fact that in captivity three weeks is
the usual period which intervenes between two cestri in such
animals, and the extreme probability that individual females do
not experience oestrus at exactly the same time, predispose one to
believe that they are monoastrous in the wild state : but, if the
limit of time for coition is three weeks, there is still just time for
the females to undergo two dioestrous cycles, and it is this possibility
which prevents positive assertion on the matter.

des Rehes, Giessen, 1854) rut occurs in early autumn, but the embryo is not
developed beyond the stage of segmentation in the following spring. Grohmann
(Sport in the Alps, Edinburgh, 1904) says that rut is experienced in July
and the beginning of August, but that there is a "false rut" in November.
Observations on roe-deer in Vienna showed that the period of gestation is
ten months ; for seven females which were served by one buck in July 1862
gave birth each to two young in the following May. It would appear probable,
therefore, that the ovum lies dormant during the early months of gestation.
Grohmann suggests that the " false rut " in November may have a quickening
influence on the ovum, and so cause it to develop.

1 Millais says (vol. iii., 1906) that the actual time of rut depends much on
the season. September 28, in Scotland, is called " the day of roaring." Sir
S. M. Wilson (field, October 8, 1904), however, reports a case of a stag which
roared during the whole summer in Kinveachy Forest, Boat of Garten, in
1904. Stags eat little or nothing during the rutting season, and lose weight
rapidly. During the first days of roaring they are said to suck up a mixture
of peat and water (Millais, loc. cit.).

2 Millais says (loc. cit.) that the fallow-deer in England ruts in October.
The necks of the big bucks swell greatly during the first week, and the
animals become more and more unsettled until about the 25th, when the first
calls are heard. The actual rut is short as a rule. The doe drops her calf
about the beginning of June, and rarely two or three are born at a time.
Sometimes, however, the females may come in season at irregular times, and
drop calves in any of the months after June and even as late as November.

THE GESTROUS CYCLE IN THE MAMMALIA 45

"Among captive animals, not more than two dioestrous cycles
have been observed in the gnu during one sexual season. Gazella
dorcas has two or three ; the giraffe about three ; while the eland,
nylghau, and water-buck have a series of dioestrous cycles, each
lasting three weeks, during May, June, and July each year.

"The gayal and bison, the axis and wapiti deer, on the other
hand, experience a continuous series of dioestrous cycles all the year
round, at intervals of about three weeks." 1

Heape states also that with red-deer in the Zoological Gardens
there is a very extensive series of dioestrous cycles, and that with
wapiti deer in captivity the possibility of pregnancy at any season
is only prevented by the fact that the male does not rut during the
casting and growth of the antlers.

The males of many of the other species referred to experience a
definite rutting season, like the stag in Britain.

AS already mentioned, the male camels in the Zoological Gardens
in London experience rut in early spring, or at the same time as
the sexual season of the female camels in Mongolia.2 The period of
gestation in the camel is thirteen months, so that in this animal,
as in the walrus among carnivores, the recurrence of the sexual
season is delayed by pregnancy, and conception cannot take place
oftener than once in two years.3 The same is the case with the
wild yak in the deserts of Tibet,4 and also, in all probability, with
the musk-ox in Greenland.5

The sexual season in many Ruminants is a period of intense
excitement, especially in those cases in which the males experience
a definite rut. (See above, p. 24, in Chapter I.) Thus, Catlin,6
referring to the American bisons, says : " The running season, which
is in August and September, is the time when they congregate into
such masses in some places as literally to blacken the prairies for
miles together. It is no uncommon thing at this season, at these
gatherings, to see several thousands in a mass, eddying and wheeling
about under a cloud of dust, which is raised by the bulls as they
are pawing in the dirt or engaged in desperate combats, as they
constantly are, plunging and butting at each other in the most
furious manner. In these scenes, the males are continually following
the females, and the whole mass are in a constant motion ; and all
bellowing (or ' roaring ') in deep and hollow sounds which, mingled

1 Heape, loc. dt.

2 According to Sven Hedin (Central Asia and Tibet, London, 1903) the wild
camels have a sexual season in December, January, and February, a fact which
suggests that they are polycestrous.

3 Swayne, Seventeen Trips through Somaliland, London, 1895.

4 Prjewalsky, loc. dt.

5 Lydekker, loc. dt.

6 Catlin, North American Indians, vol. i., 2nd Edition, London, 1841.

46 THE PHYSIOLOGY OF REPRODUCTION

together, seem, at the distance of a mile or two, like the noise of
distant thunder."

That the antlers are the fighting weapons in stags, and that their
growth is associated with the advent of the sexual season, after
which time they are cast off, are facts which have been already
referred to. The effects of castration upon the growth of the antlers
are described in a later chapter (p. 321).

Passing to the non-ruminating Ungulata, we find that the wild
sow has only one annual sexual season. It is not certain whether
this consists of more than a single oestrous cycle. Under domestica-
tion, however, the sow is polycestrous, and may take the boar five
weeks after parturition. The duration of the dioestrous cycle is from
two to foiir weeks, according to Fleming.1 The period of gestation
is about four months. Litters are usually produced only in spring
and autumn,2 -but by weaning the young early (or partially weaning
them), and feeding the mother liberally, it is possible to get five
litters in two years. A sanguineo-mucous flow has been observed
issuing from the genital aperture during the procestrum. At the
same time the vulva is distinctly swollen.

Wiltshire3 states that in the hippopotamus in captivity a
condition of oestrus may be experienced at regular monthly
intervals. This animal has been known to breed in Zoological
Gardens.

The inare is polyoestrous, the normal dioestrous cycle being about
three weeks and the oestrous period a week, though its actual length
may vary by three or four days.4 The sexual season in the absence
of the stallion extends throughout the spring and early summer
months, and is generally longest in the more domesticated breeds.
Professor Ewart informs me that in a pony imported from Timor,
which is in the Southern Hemisphere, oestrus was experienced in
the autumn, or at the same time as the spring in Timor (cf. camels,
p. 45). The period of gestation in the mare is eleven months, and
" heat " recurs eleven days after parturition. This is called the " foal
heat." Certain mares are irregular in the recunence of the "heat"
periods, and, in some, " foal heat " does not occur until seventeen
days after parturition instead of the usual eleven days. In
exceptional cases a mare, like a cow, may conceive at the "foal
heat " and yet take the horse three weeks later, just as though

1 Fleming, Veterinary Obstetric, London, 1878.

2 The times of breeding may be altered by farm practice. See Pearl, "The
Seasonal Distribution of Swine Breeding," Scientific Mont/tit/, September
1918. The dia-strous cycle is usually three weeks.

3 Wiltshire, he. n't. See also Ellenberger, Joe. cit., and Wallace (R), Farm
Live Stock of Great Britain, 4th Edition, London, 1907.

4 Ewart found that in Equus /</•/'• "W*/1//, M-strus lasted a week.

THE CESTROUS CYCLE IN THE MAMMALIA 47

she had failed to become pregnant.1 Heape states that, very
exceptionally, mares are momestrous. Blood has been observed in the
mare's prorestrous discharge, but it is not generally present. The
genitalia, however, are always swollen and congested, and a glutinous
secretion is generally emitted from them. The clitoris and vulva
often undergo a succession of spasmodic movements, preceded by
the discharge of small quantities of urine. Suckling mares tend to
fail in their milk supply, and the quality of the milk appears to
undergo some kind of change, as it is frequently the case that foals
during the heat periods of their dams suffer from relaxation of the
bowels or even acute diarrhoea. In mares which are not suckling
the mammary gland becomes congested and increases in size during
the heat. At the same time some mares develop great excitability,
and kick and squeal, becoming dangerous to approach and impossible
to drive. There is, however, great variation, for other animals may
pass through the "heat" period without exhibiting any well-marked
signs of their condition, which in a few instances can only be
determined by the behaviour of the mare towards the stallion.2

The elephant in captivity is said to be polycestrous, but I can find
no record of the duration of the dioestrous cycle. Since pregnancy
is very prolonged (twenty months), the sexual season cannot occur
more than once in two years ; that is, if the animals breed. The
elephant in the Zoological Gardens in London is stated to have
persistent cestrus probably for three or four days.

CETACEA

Little is definitely known about the periodicity of breeding in
Cetacea. According to Millais,3 the right whale brings forth in
March in every other year, the young being suckled for about twelve
months. The humpbacked whales, blue whales, and sperm whales

1 Wallace, loc. cit. Professor Ewart informs me that pregnant mares do
not necessarily abort as a result of taking the horse at the third, sixth, or
even ninth week of gestation.

2 Wortley Axe, "The 'Mare and the Foal," Jaw. of the Royal Agri<: $"<'.,
3rd Series, vol. ix., 1898. Ewart ("Studies on the Development of the Horse,"
Tram. Rot/. Roc. Edin., vol. li., 1915) says that the period of a-strus in mares
tends to be shorter the later in the season, and when the food becomes less
plentiful and less nutritious all external signs of ivstrus disappear. Under
favourable conditions, however, mares may become pregnant in winter.
Ewart gives the following as the periods of gestation in various Equida; : —
Asses and zebras, 358 to 385 days ; Prjewalsky's horse, 356 to 359 days ;
Celtic pony, 334 to 338 days. In coarse-headed tj pes of horse it is about the
same as in Prjewalsky's horse, but in the finer breeds the period is the same
as in the Celtic pony. In abnormal cases pregnancy may be unduly prolonged
in mares as in other animals, a maie occasionally going twelve months in foal
instead of eleven.

3 Millais, The Mammals of Great Britain, vol. iii., London, 1906.

48 THE PHYSIOLOGY OF REPRODUCTION

appear to have no regular time for breeding, but Millais says the
young of the humpbacked whales are generally born some time during
the summer. Haldane's records,1 which appear to refer to several
different whales, show that foetuses varying in length from six inches
to sixteen feet were found in animals captured at the Scottish
whaling stations in the summer of 1904. This great variation seems
to imply that there is no regular season at which whales copulate,
and that very possibly these animals are polyoestrous. Lillie 2 states
that two specimens of Balcenoptem muscnlus were taken off the west
of Ireland on 31st July 1909, and that one contained a foetus of one
foot in length, while the other had a foetus of five and a half feet in
length. Lillie says also that several female rorquals having foetuses
of different sizes were captured within a short time of one another.
These observations, therefore, are in a general way confirmatory of
those of Haldane.

According to Guldberg and Nansen,3 the porpoise copulates at
any time between June and October, the period of gestation being
ten months or longer. Meek 4 states that the testes enlarge
enormously in summer. The white-sided dolphin is said to copulate
in late summer, pregnancy being about ten months, and the white-
beaked dolphin is thought to be similar.5

Humpbacked whales and other Cetacea have been described as
indulging in amorous antics at the breeding time, rubbing against
one another and patting one another with their long fins.

CARNIVORA

In the female of the dog the average duration of the complete
oestrous cycle is six months, there being two annual " heat " periods,
typically in the spring and in the autumn. It follows, therefore,
that the bitch is monoestrous. Bitches belonging to the smaller
breeds tend to come " on heat " more frequently than those of the
larger varieties. Thus, in Irish terriers, the cycle may recur after
four months, though in this breed six months is the more ordinary
time.6 On the other hand, in Great Danes the duration of the
oestrous cycle is often as much as eight months. It would appear
that in those cases where "heat" recurs as often as every four
months, this is only when pregnancy is prevented, for more than two

1 Haldane, "Whaling, etc.," Annals of Scottish Nat. Hist., April 1905.

2 Lillie (D. G.), "Observations on the Anatomy and General Biology of some
Members of the larger Cetacea," Proc. Zool. Soc., 1910.

3 Guldberg and Nansen, On the Structure and development of the Whale,
Bergen, 1904.

4 Meek, "The Reproductive Organs of the Cetacea," Jour, of Anat., vol. Hi.,
1918.

5 Millais, loc, cit.

6 Marshall and Jolly, loc. cit.

THE CESTROUS CYCLE IN THE MAMMALIA 49

litters of pups are seldom if ever produced in a year. Stonehenge l
says that there is much individual variability in the periodicity of
the cycle, and that " heat " may recur at any interval from four up
to eleven months, but that six, five, and four months are the most
usual periods. Each bitch as a rule has her own peculiar period to
which she remains constant, unless systematically prevented from
breeding, in which case the periods tend to recur irregularly or even
cease altogether.2 It has been observed also that the recurrence of
the sexual season tends to become irregular with advancing age, and
this irrespectively of whether or not the animal is permitted to
become pregnant. The periodicity depends also to some extent upon
climate, for in Danish Greenland the dogs usually breed only once
a year.3

The proosstrurn in the bitch is characterised externally by the
vulva being swollen and moistened with mucus, and by the existence,
usually, but not absolutely invariably, of a flow of blood from the
aperture of the vagina. The length of the prooestrum is about ten
days. The sanguineous discharge generally ceases at the com-
mencement of oestrus, which may lasf for another week or ten
days.

Heape states that the winter .oestrus in some breeds does not last
so long as the summer oestrus. In certain individuals a relatively
slight mucous or.sanguineo-mucous flow takes place during the period
of tfistrus, and may even be continued beyond it, but this is
exceptional. Stonehenge states that a bitch will not, as a rule,
receive the dog until external bleeding has subsided, and that the
most favourable time for successful coition is about the eleventh day
of " heat " (in other words, at the beginning of the period of oestrus).
This statement is fully borne out by dog-breeders.

The external changes which occur during " heat " are accompanied
by changes in the metabolism, for Potthast,4 working on the nitrogen
metabolism of the bitch, records a slight retention of nitrogen during
the " heat " period. A similar result was obtained by Hagemann,5
who states that the retention is followed by a loss of nitrogen after
copulation. Murlin6 also shows that the effect of the prooestrum
" is to cause a retention of nitrogen, which may be explained, in part

1 Stonehenge, The Dog in Health and Disease, 4th Edition, London, 1887.

2 Heape, loc. cit.

3 Rink, Danish Greenland, London, 1877.

4 Potthast, "Kenntniss des Eiweissumsatzes," Dissertation, Leipzig, 1887.

'"' Hagemann, "Eiweissumsatz im tierischen Organismus," Dissertation,
Erlangen, 1891. Cf. also Schorndorff, "Einfluss der Schilddriise auf den
Stoffwechsel," PAiig'er's Arch., vol. Ixvii., 1897.

6 Murlin, "The Metabolism of Development. II. Nitrogen Balance during
Pregnancy and Menstruation of the Dog," Amer. Jour, of PhysioL, vol. xxvii.,
1910.

So THE PHYSIOLOGY OF REPRODUCTION

at least, as a compensation for the amount of blood lost." These
results should be compared with those recorded for menstruating
women (see p. 63 ; also p. 391 and Chapter XI.).

The histological changes whicli take place in the uterus during
the oestrous cycle are described in the next chapter.

The period of gestation in the dog varies from fifty-nine to sixty-
three days. With dogs belonging to the smaller breeds the period
is often somewhat less than with large dogs. The period of lactation
is very variable in duration, and may extend until the commencement
of the next prooestrum. Pseudo-pregnancy may occur in the dog.

The wild dog of South America (Canis azarci), according to
liengger,1 breeds only in winter, and therefore but once a year.
The same is said to be the case with the wolf 2 and the fox in their
wild state ; but these animals, in the Zoological Gardens in London,
experience two annual "heat" periods like the dog.3 The wolves
in the Dublin Gardens, however, are stated to have only one annual
sexual season when permitted to breed ; otherwise they come " in
heat" more frequently, but are always monoestrous.4 The period of
gestation in the wolf and fax is approximately the same as in the
dog, i.e. about two calendar months.

Bischoff 5 refers to the fact that the sexual season of the fox is
affected by the nature of the country which it inhabits, foxes which
live at high altitudes breeding later than those residing on the
plains. Millais6 says that fox -cubs in most parts of Britain are
not born until the end of March or beginning of April, whereas,
in the South of England, they are often produced as early as
January.

The Cape hunting-dog (Lyceum pictus) has been known to have
bred in captivity on several occasions, and notably in the Gardens
at Dublin, where six litters were produced from a single pair between
January 1896 and January 1900. The first three litters were born
in January, the fourth in November 1898, the fifth in May 1899,
and the sixth in January 1900. Cunningham writes : " It is not
easy to offer a satisfactory explanation of the irregularity of the
fourth and fifth litters. I am inclined to believe, however, in the
absence of definite information on this point obtained from the animals

1 Eengger, NatwgescJdchte d. Saugethiere row Paraguay , Basel, 1830.

2 John Hunter (Animal (Economy, London, 1786) says wolves breed in
December.

3 Heape, loc. cit.

4 For the information regarding the breeding of the animals in the Royal
Zoological Society's Gardens, Dublin, I am indebted to the late Professor D. J.
Cunningham and Dr. R. F. Scharf. (See Marshall and .Tolly, loc. cit.}

* Bischoff, " Ueber die Rauhzeit des Fuchses und die erste Entwicklung
seines Eies," Sitz. der Matk.-phys., Wien, Classe vom 13 Juni, vol. ii., 1863.
c Millais, /or. cit.

THE CESTROUS CYCLE IN THE MAMMALIA 51

in a state of nature, that the lycaon breeds only once a year, and
that the irregularity noticeable in the fourth and fifth litters is due
to a tendency on the part of the Dublin specimens to adapt them-
selves to the climatic conditions of Ireland. At the same time it
should be mentioned that certain indications were observed in
connection with the demeanour of the parents towards each other
which seemed to indicate that the sexual instinct was excited at
more than one period of the year." The period of gestation was
ascertained to be about eighty days, or nearly three weeks longer
than in the domestic dog. " As might be expected, the young when
they are born are more lusty and more advanced in development
than new-born puppies of the dog." On one occasion, when the
litter produced was unusually large, the gestation period was
lengthened to eighty-six days.1

The female of the domestic cat generally breeds two or three
times a year. According to Spallanzani 2 the " heat " periods occur
in February, June, and October, but there can be no doubt that
many individuals breed at other times, and that there is great
variation.3 Heape 4 says that there may be no less than four sexual
seasons within a year, but this can only be when the cats are not
allowed to become pregnant. The usual number of litters, in my
experience, is two, in typical cases in spring and autumn as in the
dog. Heape states also that feral cats breed only once a year. The
domestic cat is polyoestrous, and may experience a long succession
of diojstrous cycles in one sexual season, each dicestrous cycle lasting
about fourteen days and sometimes less.5 The period of gestation is

*/ O

from fifty-six to sixty-three days.6

Millais " says it is uncertain whether the wild cat has one or two

1 Cunningham (D. J.), " Cape Hunting Dogs (Li/coon pictus) in the Gardens
of the Boyal Zoological Society of Ireland," Proc. Roy. Hoc. Edin., vol. xxv.,
1905.

2 Spallanzani, Dissertations, vol. ii., London, 1784.

3 Marshall and Jolly, Joe. cit. I have known a cat experience cestrus
regularly at intervals of about a fortnight from December until the following
August, but such a long succession of durstrous cycles is probably unusual.

4 Heape, loc. fit.

5 Heape, loc. cit. Mr. W. O. Backhouse informs me that in his experience
with Siamese cats the females, if the kittens are destroyed or birth is premature,
come on heat regularly about eight days after parturition. This ' probably
occurs in other breeds, at any rate in spring and summer.

6 There is some evidence that cats, like rabbits, may experience pseudo-
pregnancy after sterile coition, since milk secretion may occur. See p. 131.
(Doncaster, "A Possible Connection between Abnormal Sex-Limited Trans-
mission and Sterility," Proc. Camb. Phil. *S'oc, vol. xvii., 1914). Barrington
shows that the glandular epithelium of Bartholin's glands in cats becomes
rich in mucin shortly before <estrus and in the last half of pregnancy. ("The
Variations in the Mucin Content of the Bulbo-Urethral Glands," Internal.
MonaU&chr. f. Anat. ttnd P/ii/*.t vol. xxx., 1913.)

7 Millais, loc. cit. I am much indebted to Mr. A. H. Cocks for supplying
me with interesting information concerning various Carnivora in captivity.

52 THE PHYSIOLOGY OF REPRODUCTION

annual breeding seasons. The probability is that there is only one
(in March), the young being born in May ; but Millais records that
he has seen young wild cats, which could not have been more than
forty days old, killed in Scotland in October. Cocks, in a letter
quoted by Millais, says that he has received wild cats which, judging
from their size, were probably born in August or September, and
that in captivity he has observed a female experience " heat " during
the summer. " Many years, when owing to the death of the young,
or the fact that the pair had not bred -together in the spring, I have
kept male and female together all summer, but they showed no
inclination to breed." In a more recent letter to the author
Mr. Cocks states that the old female wild cat in his possession came
" in season " and received the male in the autumn of 1904, after the
death of the kittens which were born earlier in the same year. The
animal, however, failed to become pregnant. In the experience of
this observer the commonest month for wild kittens is May, but the
range of dates in his collection varies from 20th April to 22nd July.
The period of gestation was ascertained to be sixty-eight days. The
period of oestrus was observed to last for five days, or about the same
time as in the domestic cat.

The male wild cat has a definite season of rut (like the stag), and
calls loudly and incessantly, making far more noise than the female
cat.1 This information is interesting, since the males of most
Carnivora, so far as is known, do not experience anything of the
nature of a recurrent rutting season, although many individuals
show indication of increased sexual activity at some times more
than at others. So far as I am aware, nothing of the nature of a
rutting season is ever known in the males of the domestic cat, dog,
or ferret, all of which seem to be capable of coition at any period of
the year. On the other hand, the males of certain seals appear to
possess a season of rut at the same time as the sexual season in the
females.

Little is known definitely regarding the breeding habits of the
larger FelidiB in their wild state, beyond the fact that they probably
agree in having a single annual sexual season. In captivity certain
of them, at any rate, are polycestrous. Thus, in the lioness oestrus
has been known to recur at intervals of three weeks until the animal
became pregnant, while the period of oastrus may itself last a week.2
Further, the lioness may experience three or four sexual seasons in
the year, as in the domestic cat, this having been observed to occur
in the lioness in the Dublin Zoological Gardens when copulation had

1 I am indebted to Mr. Cocks for information regarding the breeding habits
of the wild cat.

2 See Marshall and Jolly, loc. tit.

THE CESTROUS CYCLE IN THE MAMMALIA 53

not been successful, or when the animals were not permitted to breed.
If allowed to become pregnant the lioness at Dublin may still experi-
ence two sexual seasons, and have two litters of cubs within the
year. The puma in the Dublin Gardens is stated to have one sexual
season annually if breeding, or two if there is no gestation. The
larger Felidte as a rule breed comparatively freely in confinement,
some places, such as the Dublin Gardens, being famous for successful
lion breeding. The period of gestation in the lioness is from fifteen
to sixteen weeks ; that of the tigress is about twenty-two weeks ;
while the puma goes with young for fifteen weeks.

Most species of bears, both in their wild state and in confinement,
are rnonoestrous and have one annual sexual season. The grizzly
bear, however, according to Somerset,1 bears young only once in two
years. The bears in the Zoological Gardens at Dublin, on the other
hand, may experience more than one annual sexual season if
pregnancy does not occur. The period of gestation in the brown
bear is seven months; in the grizzly bear it is probably longer.
Heape states that with the bears in the Zoological Gardens in
London oestrus may be experienced for two or three months
continuously; but this condition, as he points out, is unnatural and
probably an effect of confinement, for though coition can occur, it
does not, as a rule, result in pregnancy.

The ferret, which is a domesticated variety of the polecat, is
monoestrous, but may have as many as three annual sexual seasons,2
which, however, instead of being distributed at regular intervals
throughout the year, occur only in the spring and summer, the
autumn and winter being occupied usually by a prolonged anoestrous
period.3 This tendency towards a concentration of sexual seasons
during one part of the year may be considered as an approach to a
condition of poly oestrum ; for, if the cestrous periods were to recur
at still shorter intervals than is actually the case, they could be
regarded as forming so many dicestrous cycles in one sexual season.
So far as I am aware, the ferret does not experience osstru's more
than twice annually if allowed to breed.

The polecat is also moncestrous, but breeds only once a year.
Mr. Cocks informs me that in captivity the young of this animal are
generally born in the first half of June, and that the gestation period,
as in the ferret, is about forty days.

The stoat, weasel, and pine- marten, in their wild state, are almost

1 Somerset. Quoted by Heape, loc. cit.

2 Carnegie, Ferrets and Ferreting, London.

3 Robinson ("The Formation, Rupture, and Closure of Ovarian Follicles in
Ferrets, etc.," Trans. Roy. Soc. Edin., vol. Hi., 1918) finds that the size of the
ovary varies at different periods. It is smallest in the ancestrum and largest
about mid-pregnancy. At oestrus it is intermediate.

54 THE PHYSIOLOGY OF REPRODUCTION

certainly mon<iestrous and breed once a year. In the last-mentioned
animal Cocks l found that a single oastrus may last a fortnight. The
stoat and weasel do not appear to have been bred in captivity. The
otter in a state of nature breeds only once a twelvemonth (in winter,
as a rule, but young may be born at any season according to Cocks).
In captivity, however, oestrus may recur at regular monthly intervals
all the year round.2

The various species of seals are in all probability moncestrous,
and have one litter of young annually. Some species show an almost
perfect rhythmic regularity in the recurrence of their breeding
season. Thus, in the case of the harp seal in the north-east of
Newfoundland, and also in Greenland, according to Millais,3 the pups
are born each year between 8th and 10th March. Farther north,
however, at Jan Mayen, they are not born until about 23rd or 24th
March. Turner's notes 4 on the breeding habits of seals also point to
the conclusion that the sexual season with these animals is restricted
to" regular periods of comparatively short duration, so that it may
probably be assumed that seals are monoestrous. The males of
seals, as already remarked, experience rut at the time of the female
sexual season. Whether the male generative organs are functional
(e.g. whether the testes produce sperms) at other times does not
appear to be known. It is of interest to note that in many species
the rut is experienced during a period of complete fasting. Thus it
is stated that the male fur seal, after coming to land, may live for
over a hundred days without taking food, and that during this period
he is constantly engaged in struggles with other males, finally
leaving the shore in a state of extreme emaciation.

The walrus affords an example of a mammal which bears young
only once in three years. Parturition takes place about May or
June, and the sexual season recurs about two years subsequently.

1 Cocks, "Note on the Gestation of the Pine-Marten," Proc. Zool. Soc.,
1900.

2 Cocks, "Note on the Breeding of the Otter," Proc. Zool. 8oc., 1881.
Mr. Cocks' subsequent experience, concerning which he has been kind enough
to write to me, confirms the conclusion that there is no anoestrous period in
the otter in captivity. There has been some controversy regarding the
breeding of the badger. According to Meade- Waldo the period of gestation
is between four and five months (" The Badger: its Period of Gestation,"
Zoologist, 1894), but according to Cocks ("The Gestation of the Badger,"
Zoologist, 1903, 1904), this period may be anything between under live and
over fifteen months, for although the sexual season may apparently occur at
any time of the year, the young are invariably born within a period limited
to six weeks. This extraordinary conclusion is based on a number of observa-
tions. Fries ("Tiber die Fortpflanzung von Mvd.-s tii.m.s," Zool. Anz., vol. iii.,
1880) describes the badger's ovum as undergoing a resting state during which
development is at a standstifl (cf. roe-deer, p. 43).

3 Millais, loc. cit.

4 Turner, "On the Placentation of Seals," Trans. Roy. Soc. Edin., vol.
xxvii., 1875.

THE CESTROUS CYCLE IN THE MAMMALIA 55

Thus the nursing or lactation period extends for nearly two years,
while gestation lasts about one year.1

IXSECTIVORA

The majority of the animals in this order are almost certainly
polyoestrous, but comparatively little is known concerning their
breeding habits. The shrew in this country may be found breeding
in any month from April until November, so that it is practically
certain that this animal is polyosstrous, and may have two litters, if
not three litters, in a year. It is extremely probable also that the
water-shrew breeds twice a year. In the hedgehog, in this country,
litters are born at the end of May or June, and in August or
September.'2 In Germany it is said that the breeding season extends
from March until July.3 The period of gestation in the hedgehog is
not more than one month. The Malayan hedgehogs Gymnura
and Hyloinys are stated to experience an uninterrupted polycestrum.

In the mole a great development of the male generative organs
begins to take place at the end of January, culminating at the
end of March. Previous to the end of January it is a matter of
great difficulty to distinguish the males from the females without
having recourse to dissection. The testicles lie on each side of the
urinary bladder within the peritoneal cavity. In March they are
protruded into sacs, which look like a continuation of the peritoneal
cavity beneath the base of the tail. According to Regaud and
Lecaillon they increase in size sixty-four times.4 Meanwhile the
seminiferous tubules within the testicles undergo enlargement, and
cells are proliferated, which give origin to the spermatozoa. The
prostatic glands, which begin to increase in size in February,
acquire enormous dimensions, and conceal the urinary bladder at the
end of March5 (rf. hedgehog, p. 250). At the beginning of the
breeding season the male moles tight one another with great ferocity,
and one is often killed. Pairing takes place at the end of March, or

1 Millais, loc. cit.

2 Millais, The Mammals of Great Britain and Ireland, vol. i., London, 1904.

3 Van Herwerden, " Beitrag zur Kenntniss des menstruellen Cyklus,"
Monatsschr. f. Geburtshiilfe und Gynak., vol. xxiv., 1906. For further informa-
tion see Marshall, "The Male Generative Cycle in the Hedgehog," Jour, of
Physiol., vol. xliii., 1911 ; and Tandler and Gross, Arch. f. Entwick. Mech.,
vol. xxxiii., 1911.

4 Adams, "Sexual Life of Mole," Jour. Ministry of Agric., vol. xxxvii., 1920.
Regaud, "Etat des Cellules Interstialles chez la Taupe," C.R. de VAssoc. Anat.,
Suppl., 1904. Lecaillon, "Sui- les Cellules Interstialles du Testicule de la
Taupe," CM. de la Soc. de Biol., vol. Ixvi., 1909.

6 Owen, loc. cit. The same authority states that in the Cape mole (Chryso-
chloris) he found the testes near the kidneys, but that the vasa deferentia had
a convoluted course, which showed that they underwent periodic movements.
Owen also describes the vesiculse seminales in the hedgehog as growing to an
enormous size at the season of rut.

56 THE PHYSIOLOGY OF REPRODUCTION

in April, or sometimes as late as early May. A second litter of
moles may be born later in tbe year, but this fact has not been
definitely proved.1

It would appear that in some Insectivores the prooostrum may be
comparatively severe, for in Tupaia javanica Stratz 2 has described a
" menstrual " blood-clot which contained pieces of desquamated
epithelium.

CHEIROPTERA

As will be explained more fully in a future chapter, spine species
of bats appear to be exceptional in that the season of osstrus does
not synchronise with the period of ovulation. It has been shown by
Benecke,3 Eimer,4 van Beneden/' and Salvi, that whereas copulation
may occur in the autumn, the ova are riot fertilised until after the
winter hibernation, the spermatozoa in the meantime lying dormant.
Salvi,6 however, describes the bats in the Grotta dell' Inferno, near
Sassari, as copulating also in the spring, but it is suggested that
coition at this season may only take place among those females which
have failed to become inseminated effectively in the previous autumn.7
It does not appear to be known whether the polyoestrous condition
ever occurs in bats.

It is stated that a " menstrual " (prooastrous) flow has been
observed in the flying fox (Pteropus)?

PRIMATES

Lemurs. — Among Lemuroids, Stratz9 has shown that in Tarsius
spectrum there is a sanguineous procestrous discharge almost as
concentrated as in monkeys. This is presumably followed by an
O3strous period. It is stated also that Tarsius experiences an
uninterrupted series of dioastrous cycles (i.e. a 'condition of continuous
polycestrum) ; but that, whereas conception is possible at any time of
the year, breeding occurs more frequently in October and November
than at other seasons.10

1 Millais, loc. cit. See also Adams, " A Contribution to our Knowledge of
the Mole," Manchester Lit. and Phil. Soc. Mem., 1902.

2 Stratz, Der yeschlechtsreife Saiigethiereierstock, Haag, 1898.

3 Benecke, "Ueber Reifung und Befruchtung des Eies bei den Fleder-
mausen," Zool. Anz., vol. ii., 1879.

4 Eimer, "Ueber die Fortpflanzung der Flederiuause," Zool. Am., vol. ii.,
1879.

6 Van Beneden, " Observations sur la Maturation, la Fecondation, et la
Segmentation de 1'ceuf chez les Cheiropteres," Arch, de Biol., vol. i., 1880.

6 Salvi, "Osservazioni sopra 1'Accoppiamento dei Chirotteri nostrani," Atti
della Societa Toscana di Scienze Naturah, vol. xii., 1901.

7 Duval, Etudes sur U Embryologie des Cheiropteres, Premiere Partie, Paris,
1899.

8 Wiltshire, loc. cit. ° Stratz, loc. -cit. 10 Van Herwerden, loc. cit.

THE CESTROUS CYCLE IN THE MAMMALIA 57

Monkeys. — The essential similarity between the procestrum in the
lower Mammalia and menstruation in monkeys will be made clear in
the next chapter, when the histological changes which occur in the
uterus are described. The consideration of the subject, however, is
somewhat complicated by the fact pointed out by Heape1 that,
whereas monkeys may have a continuous series of dicestrous cycles
usually at regular monthly intervals, they are not necessarily capable
of breeding at every heat period. Thus there is evidence that in
the gorilla and chimpanzee in West Africa and in the orang-utan
of Borneo and the Eastern Archipelago there are special sexual
seasons,2 and Heape 3 has shown that the same can be said of Semno-
pithccits entt'llus arid Macacus rhesus in India, but that the exact time
for breeding varies in the different localities. Thus in Simla Macacus
rhesus copulates about October, and gives birth to young about
August or September in the following year, whereas on the plains
around Muttra it seems probable that March is the usual month
when young are born. Kingston4 states that in the Himalayas
the Rhesus monkeys pair in September and the young are born in
March. However, Mr. Sanyal, the Superintendent of the Zoological
Gardens in Calcutta, expressed the opinion that M. rhesus can breed
at all times of the year.3 On the other hand, it has been shown by
van Herwerden 5 that Cercocebus in the island of Banha breeds only,
as a rule, in the late summer or early autumn.

Heape 6 states that with the Macacus in the .Gardens in London
there is definite oestrus which always occurs after the cessation of the
menstrual discharge, and persists for two or three days, and Ellis7
has shown that this is also probably the case with the orang-utan
as well as with various monkeys.

Pocock8 has given some interesting details concerning the
phenomena which attend the menstrual process in various monkeys
and baboons in the Zoological Society's Gardens. He states that the
females of many species at about the time of menstruation exhibit
extreme congestion of the naked area surrounding the genital and

1 Heape, loc. cit.

- Win wood Reade, Savage Africa, London. Molirike, Das Ausland, 1872.
Garner, Gorillas and Chimpanzees, 1896. Burton (Trips to Gorilla Land, vol. i.,
London, 1876) says that the gorilla breeds about December, a cool, dry month,
and that the period of gestation is five to six months.

3 Heape, "The Menstruation of Semnopithecus entellus," Phil. Trans., B.,
vol. clxxxv., 1894, "The Menstruation and Ovulation of Macacus rhesus,"
Phil. Trans., B., vol. clxxxviii., 1897.

4 Kingston, .1 Xaturalist in Himalaya, London, 1920.

5 Van Herwerden, loc. cit.

6 Heape, The Sexual Season, etc.

7 Havelock Ellis, Psychology of Sex, vol. ii., Philadelphia, 1900.

8 Pocock, " Notes upon Menstruation, Gestation, and Parturition of some
Monkeys that have lived in the Society's Gardens," Proc. Zool. Soc., 1906.

58 THE PHYSIOLOGY OF REPRODUCTION

anal orifices. Such a swelling was noticed in various species of
Cercocebus and Papi,o, and in Macacus nemestrinus^ but not in
Cercopitkecus, or in certain other species of M<IC<«-H* including M.
rhesus. Heape, however, states that in menstruating specimens of
M. rhesus observed by him, and M. cynomolgus, the skin of the
buttocks became swollen and red or purple in colour, as well as the
skin of the abdomen,, the inside of the thighs, and the under surface
of the tail, while the skin of the face tended to become flushed or
blotched with red; at the same time the*nipples and vulva were
congested. Menstrual ha-morrhage has been recorded in many
monkeys and baboons, but there appears to be considerable variability
in its extent. Pocock says : " In baboons it may or may not take
place, and may be great or little in amount. It has been noticed to
occur in some profusion in a female of Macacus sinicm, and not to
occur appreciably in a female of the closely allied species, M.
fascicularis. Obviously, therefore, it cannot be associated with the
inflammatory swelling of the genito-anal region [since no swelling
was apparent in either of these two species] ; and it is hardly likely
to have a specific value in taxonomy. Perhaps the nearest guess
that can at present be made is the surmise that it is dependent on
the constitution or health of the individual."

Heape noticed that in M. rhesus the menstrual discharge lasted
for from three to five days. Pocock records that in a Chacma
baboon ( Papio porcarius) haemorrhage continued for about four days.
In both animals the phenomenon was truly "menstrual" (i.e. of
monthly occurrence).

Pocock records the interesting fact that whereas the swelling of
the congested area commences at about the same time as the
haemorrhage, it does not reach its full size until several days after
the discharge is over. It soon afterwards begins to shrink, and in
about another two weeks has disappeared, so that the female at a
distance is indistinguishable from the male. After a few days' rest
congestion again sets in, and the process is repeated. Pocock
suggests that this sub-caudal swelling may serve the purpose of
apprising the male (at a distance) as to when the female is "on
heat," and it is to be noted that it is at its maximum after
menstruation is over (as just mentioned), and so presumably
therefore during a definite period of osstrus.

The question as to the correspondence in time between the
processes of menstruation and ovulation is discussed in a later
chapter.

1 Similar observations had been previously described in Cercopithecm, Papio,
and other species by certain of the older naturalists. See St. Hilaire and
Cuvier, Hist. Nat. des Mammiferes, 1819-35.

THE CESTROUS CYCLE IN THE MAMMALIA 59

Little is definitely known concerning the length of the gestation
period in the various apes and monkeys. Pocock's observations
show that in Macaciis nemestrinus this period is between six and
seven months. Blandford l states his belief that about seven months
is the usual period for the genus Macacus. Sanyal, according to
information recorded by Sclater,2 found that a female of Cercopithecus
cynomrus in the Zoological Gardens, Calcutta, carried her young for
seven months.

Gestation in the Quadrumana is dealt with at some length by
Breschet,3 who cites many of the older observations. He shows that
the question as to the duration of the period is complicated by the
fact that monkeys, unlike the majority of Mammals, may copulate at
other times than the breeding season, and that they are said
occasionally to experience menstruation during pregnancy.

Man. — As is well known, menstruation recurs normally in the
non-pregnant human female at intervals of from twenty-eight to
thirty days. The exceptions to this general rule are, however, very
numerous, and have often been noticed. Thus the interval may be
extended to five weeks, or be abbreviated to two weeks without any
derangement to the general health. " In one hundred women, sixty-
one [were found] to menstruate every month, twenty-eight every
three weeks, ten at uncertain intervals, and one, a healthy woman
aged twenty-three years, every fortnight."4 The duration and
amount of the discharge may also vary considerably both in different
women and in the same woman at different times.

It has been supposed by many from classical times onwards, that
menstruation is directly associated with lunar periodicity. Thus
Aristotle5 says that it occurs during the waning of the moon. In
recent times Arrhenius,6 as a result of a statistical examination of
12,000 cases, found a periodicity corresponding to the tropical lunar
month of 27'32 days (and not to the synodic period of 29'53
days, and hence with the moon's phases); that is to say, that

although women menstruate at all times, yet more do so at a certain

0

1 Blandford, The Fauna of British India, vol. i., London, 1888.

2 Sclater, Mammals of South Africa, London.

3 Breschet, "Recherches anatomiques et physiologiques sur la Gestation
des Quadrumanes," Memoires de VAcad. des Sciences, vol. xix., 1845.

4 Laycock, loc. cit., and Havelock Ellis, loc. cit. There is in some cases a
tendency for the cycle to become divided up into two cycles, separated by
the so-called " Mittelschmerz," or inter-menstrual pain, which is occasionally
accompanied by a sanguineous discharge. (Halliday Groom, " Mittelschmerz,"
Trans. Edin. Obstet. Soc., vol. xxi., 1896.)

6 Aristotle, Historia Animalium (The Works of Aristotle, vol. iv., Thompson's
Translation, Oxford, 1910) and De Generatione Animalium (vol. v., Platt's
Translation, Oxford, 1912).

6 Arrhenius, " Die Einwirkung kosmischer Einflusse an physiologischen
Verhaltnisse," Skandin. Arch. f. Physiol., vol. viii., 1898.

60 THE PHYSIOLOGY OF REPRODUCTION

part of the tropical lunar period than at other parts. The inference
drawn is that the moon's declination may have been one factor
among a number that determine the time of menstruation. Such
a conclusion, however, must be accepted with great reservation
seeing that the dioestrous cycle in the lower Mammals may be three
weeks or fifteen days, or some other period having no relation to
lunar periodicity.

It is stated, also, that the periodicity of menstruation depends
partly on the climatic conditions, and that women in Lapland and
Greenland menstruate less frequently, whereas in certain low and
hot countries the catamenia may recur every three weeks.1

Further, the regularity with which the menstrual periods occur
is liable to be disturbed by environmental changes. Thus, it is
stated that change of residence, or foreign travel, without otherwise
affecting the health, may bring about amenorrhoaa or a temporary
cessation of menstruation.2 Such an effect is, no doubt, comparable
to the well-known influence of captivity or change of environment in
arresting the sexual functions of many animals.

The commonest time for the continuance of the menstrual flow is
said to be about three or four days in this country, but it may last
for as long as eight days, or, on the other hand, for only a few hours
without disturbance of health. It usually begins gradually, becoming
most profuse about the second or third day, and then diminishes.3
The total amount of blood lost has been variously estimated at from
two to four ounces. In hot climates the quantity is greater than
in cold ; and it is said to be increased by luxurious living, and also
by abnormal mental stimulation. The character of the menstrual
discharge and its source of origin can best be considered in describing
the histology of the uterus during the oastrous and menstrual cycles
(see Chapter III.).

The monthly development of the uterine mucous membrane
which precedes the menstrual discharge is often accompanied by a
fullness of the breasts which begins to disappear after the commence-
ment of the flow. Swelling oi' the thyroid and parotid glands, and
tonsils, as well as congestion of the skin and a tendency towards the

1 Matthews Duncan, " Sterility in Women," 'Brit. Med. Jour., 1883 ; and
Laycock, loc. cit.

2 Wiltshire, loc. cit.

3 Galabin, .1 Manual of Midwifery, 6th Edition, London, 1904. The age
at which menstruation begins varies in different countries, being earlier in
warm climates than in cold ones. In our own country the first menstruation
does not usually occur before the age of fourteen or fifteen, while the meno-
pause (or period when menstruation ceases) begins about the age of forty-five.
(See p. 715.) Kennedy (Edin. Med. Jour., vol. xxvii., 1882), however, has
reported a case of a woman who continued to menstruate after giving birth
to a child at the age of sixty-three.

THE CESTROUS CYCLE IN THE MAMMALIA 61

formation of pigment, are also known to occur.1 The voice also is
liable to be affected at the menstrual periods, and the skin and
breath sometimes have a peculiar odour. Mental depression may
exist, and be accompanied by nervous pathological phenomena.

Many women are more excitable before the onset of menstruation
and others during the process. With the onset the pulse-rate, blood
pressure, and temperature generally rise. The bacterial resistance
of the subject is reduced. After menstruation there is a period of
slackness, sometimes associated with headache and depression.

As Head has pointed out, the general bodily state at the menstrual
periods forms a potent cause of diminished automatic control by
the central nervous system. "This physiological act may be
accompanied by referred pain, confined strictly to those segments
which stand in direct relation with the pelvic organs, or the morbid
sensations may occupy the whole of the body and lower extremities
below the level of the umbilicus, with or without the cervical areas
and occipital region of the scalp. Finally, the head, trunk, and even
the limbs may become painful and tender in parts that have no
direct relation to stimuli within the pelvic organs. The extent to
which such widespread generalisation occurs, depends more on the
temperamental condition of the patient than on the intensity of the
painful irritation."2 This diffusion of painful sensation is due to
diminished central resistance ; potentially painful impulses which
would normally have been inhibited or strictly confined to areas
appropriate to the organ affected are allowed to spread widely.
There is a tendency during menstruation to react more vividly to
any excitation capable of evoking discomfort.

Painful menstruation, when so pronounced as to be considered
pathological, is called dysmenorrhoea ; diffuse or protracted menstrua-
tion is termed menorrhagia; but there are all gradations between
these conditions and normality.3

According to the upholders of the " Wellenbewegung " hypothesis4
the reproductive life of the human female consists of a succession of
wave-like periods which follow the monthly cycle. Thus, according
to Stevenson,5 the curve of temperature is above the mean line for

1 See p. 384, Chapter IX.

2 Head, "The Release of Function in the Nervous System," Croonian
Lecture, Proc. Roy. <S'oc., B., vol. xcii., 1921.

:! For amenorrhoea, see pp. 60 and 69.

4 Godman, "The Cyclical Theory of Menstruation," Amer. Jour. Obstet.,
vol. xi., 1878. Reinl, "Die Wellenbewegung des Lebensprozesses des Weibes,"
Volkmann's Sammlung liin. Vortrage, No. 273. Ott, "Les lois de la periodicite
de la fonction physiologique dans 1'organisme feminine," Nouvelles Arch.
cPObstet. et de Gyne'c., 1890. See also Havelock Ellis, Nan and Woman : a Study
of Human Secondary Sexual Characters, 5th Edition, London, 1914. This work
contains a fund of valuable information.

5 Stevenson, "On the Menstrual Wave," Amer. Jour. Obstet., vol. xv., 1882.

62

THE PHYSIOLOGY OF REPRODUCTION

about half the month, when it rises to half a degree above the mean.
It falls below the mean line just before the onset of menstruation,
during which it remains about half a degree below. Similar results
were obtained by Reiul, Ott, and Giles,1 but Vicarelli 2 and certain
other authors have recorded an increased temperature during
menstruation.3 Zuntz,4 however, as a result of more recent experi-
ments, says that there is a regular lowering of the temperature
throughout the menstrual period, after which it rises to the normal.
Stevenson states also that the curve of urea excretion follows

25

FIG. 1. — Diagram illustrating the " Wellenbewegung " hypothesis. The
curve AB represents the varying intensity of the vital processes
during the twenty-eight days of the menstrual cycle. The numbers
between m and n represent the days occupied by menstruation.
(From Sellheim.)

a similar course to the temperature curve, and that, speaking
generally, there is an increase in metabolism coincident with the
time of development of the uterine mucosa. There is, however, no
doubt much truth in von Noorden's criticism 5 that the " menstrual
wave " hypothesis has given occasion to many premature conclusions

1 Giles, "The Cyclical or Wave Theory, etc.," Trans. Obstet. Soc., London,
vol. xxxix., 1897.

2 Vicarelli, " La temperature de Puterus dans ses diverses conditions
physiologiques," Arch. Ital. de Biol., vol. xxxii., 1899.

3 Sfameni, " Influence de la menstruation sur la quantite d'h&uoglobine,"
Arch. Ital. de Biol., vol. xxxii., 1899.

4 Zuntz (L.), "Einfluss der Ovarien auf den Stoffwechsel," Arch. f. Gyntik.,
vol. Ixxviii., 1906.

5 Von Noorden, Metabolism and Practical Medicine (English Translation),
vol. i., London, 1907.

THE CESTROUS CYCLE IN THE MAMMALIA 63

regarding the behaviour of the metabolism. Schroder,1 who investi-
gated the nitrogen metabolism, found a retention of nitrogen
immediately before and during menstruation (cf. Potthast, etc., for
dogs, p. 49), but other investigators have obtained somewhat different
results.2 Zuntz has shown from numerous experiments that, contrary
to the conclusions of other authors, there is no evidence of a
constant variation in the respiratory exchange during the menstmial
cycle. (For changes during pregnancy, see Chapter XI.)

Mosher 3 states that there is a fall of blood pressure at the time
of menstruation. Zuntz4 records a diminution in the pulse-rate.

Sfameni5 states that there is a decrease in the quantity of
haemoglobin in the blood during menstruation. He says also that
the number of blood corpuscles increases in the days immediately
preceding the hemorrhage, but is diminished during it.6

Birnbaum and Osten7 state that in the blood of menstruating
women coagulation is retarded. This statement is based on
experiments made by adding fibrinogen to menstrual blood-serum.

Blair Bell 8 states that in connection with menstruation there is
a marked drop in the calcium content of the systemic blood, and
that this is most marked just before bleeding begins. This is
correlated with an excretion of calcium salts in the menstrual
discharge, an examination of which revealed the presence of a
considerable quantity of calcium, both free and within the leucocytes
(see p. 81). This excretion of calcium during menstruation is
regarded by Blair Bell as connected phylogenetically with the
process of egg-formation by birds and other lower Vertebrates.

Further, this author is disposed to believe that the calcium
metabolism, under the direction of the ovaries and other ductless
glands, is concerned in the phenomena of menstruation. He refers
especially to the following points: (1) Calcium salts are necessary
for the repair of all lesions. Therefore the presence of menstruation
is dependent upon a healthy condition of the organism, and its
claims on the calcium metabolism at any particular time (cf. absence

1 Schroder, " Untersuchungen iiber den Stoffwechsel wahrend der Men-
struation," Zeitschr. f. Mm. Medicin, vol. xxv., 1894.

2 See von Noorden, loc. cit.

3 Mosher, "Blood-pressure during Menstruation," Johns Hopkins Hospital
Bulletin, 1901.

4 Zuntz, loc. cit.

5 Sfameni, loc. cit.

6 Cf. Carnot and Deflandre, "Variations du nombre des Hematics chez la
Femme pendant la periode menstruelle," C. R. de la Soc. de Biol.t vol. Ixvi.,
1909.

7 Birnbaum and Osten, " Untersuchungen iiber die Gerinnung des Blutes
wahrend der Menstruation," Arch. f. (jyniik., vol. Ixxx., 1906.

8 Blair Bell, " Menstruation and its Relation to the Calcium Metabolism,"
Proc. Roy. Soc. Med., July 1908. See also below, p. 389.

64 THE PHYSIOLOGY OF REPRODUCTION

of menstruation during lactation when calcium salts in quantity are
required for the milk). (2) Uterine contractions are, like other
involuntary muscle contractions, largely dependent upon the calcium
salts circulating in the blood. (3) Calcium salts have a powerful
effect on the vasomotor system, which is greatly affected during
menstruation and the menopause. (4) Menstruation does not begin
until puberty, when the bony framework has been laid down.1

According to Hare 2 menstruation is the result of a progressive
accumulation of carbonaceous material in the blood. In animals
excessive muscular activity is a substitute. On this view, for which
Hare presents general evidence, menstruation is a means of getting
rid of an anabolic surplus.

According to Martin,3 and certain other writers, the human
female often experiences a distinct post-menstrual osstrus, at which
sexual desire is greater than at other times ; so that, although
conception can occur throughout the inter-menstrual periods, it
would seem probable that originally coition was restricted to definite
periods of oestrus following menstrual or prooastrous periods in
women as in the females of other Mammalia. On this point Heape
writes as follows : " This special time for oastrus in the human
female has very frequently been denied, and, no doubt, modern
civilisation and modern social life do much to check the natural
sexual instinct where there is undue strain on the constitution, or
to stimulate it at other times where extreme vigour is the result.
For these reasons a definite period of oestrus may readily be
interfered with, but the instinct is, I am convinced, still marked."4

Mall,5 as a result of the study of thirty-six cases, has come to the
conclusion that fertile coition is most likely to occur between the
fourth and thirteenth days after the first day of the appearance of
the menstrual discharge. This is further evidence of a post-menstrual
oestrus. Mall supposes that there is on an average a one-day interval
between coition and the fertilisation of the ovum.

Heape has also given a brief resume of the evidence that
primitive man resembled the lower Primates in having a definite

1 Blair Bell, The Principles of (jynaicology, London, 1910.

2 Hare, "The Meaning and Mechanism of Menstruation," Clinical Journal,
1916.

3 Martin, "The Physiology and Histology of Ovulation, Menstruation, and
Fertilisation " Hirst's System of Obstetrics, vol. i., London, 1888.

4 Heape, loc. cit. According to Stopes (Married Love, London, 1918) there
may be two periods of increased sexual desire in the human subject during
one menstrual cycle, but it is not suggested that the second period is in any
way correlated with the " Mittelschmerz." If Stopes is correct it is difficult to
compare the menstrual cycle of man with the nestrous cycle of the lower
Mammals.

1918.

6 Mall, "On the Age of Human Embryos," Amer, Jonr. of Anat., vol. xxiii.,

THE (ESTROUS CYCLE IN THE MAMMALIA 65

sexual season. The evidence is based largely upon the works of
Ploss l and "Westermarck,2 the latter of whom goes somewhat fully
into the subject in a chapter on "A Human Pairing Season in
Primitive Times," to which the reader is referred for further
references on this subject.3

It has been shown that there is a more or less restricted season
for breeding among certain of the North American Indians, among
certain tribes in Hindustan, among many of the native Australians,
among the Esquimaux, among the natives of the Andaman Islands,
as well as among certain other of the more primitive races of
mankind. The season seems generally to occur in the -spring, but
this is not invariably so. Annandale and Robinson4 state that
among the Semang or aboriginal tribes of the Siamese State of Jalor,
children are generally born only in March, or immediately after the
wet season, a fact which appears to imply that there is a regular
sexual season in June.

Further evidence of the existence of a primitive sexual season in
man is furnished by the records of the annual feasts which the
ancients indulged in — usually in the spring — and which Frazer5
has shown to be represented in modern European countries by the
May-queen festivals, and other similar customs that have survived
into our own time. It is well known that the ancient festivals
among the civilised peoples of the past were times of great sexual
licence, and so in all probability were similar in origin to the
licentious feasts and dances of various savage races at the present
day. Their anthropological significance and the intimate association
between them and the idea of reproduction are discussed at great
length by Frazer in his book entitled " The Golden Bough."

There is, moreover, evidence of a human pairing season in the
higher birth-rate which occurs at certain seasons in various countries
at the present day. Ploss has collected statistics illustrating this
fact in Russia, France, Italy, and Germany, and Haycraft6 has shown
that there are indications of a similar condition existing in Scotland.
On this subject Mayo-Srnith7 writes as follows : "The largest number
[of births] almost always falls in the month of February . . . corre-

1 Ploss, Das Weib, Leipzig, 1895.

2 Westermarck, The History of Human Marriage, London, 1891 ; 5th Edition,
1921.

3 See also Havelock Ellis, loc. cit.

4 Annandale and Robinson, Fasciculi Alalayenses: Anthropology, Part I.,
1903.

5 Frazer, The Golden Bough, 2nd Edition, London, 1900 ; 3rd Edition, in
thirteen volumes, published at intervals subsequently.

c Haycraft, "On some Physiological Results of Temperature Variations,"
Trans. Roy. Soc. Edin., vol. xxix., 1880.

7 Mayo-Smith, Statistics and Sociology, vol. i., New York, 1895. Cf. also
van Herwerden, loc. cit.

66 THE PHYSIOLOGY OF REPRODUCTION

spending to conceptions in May and June. . . . Observations tend to
show the largest number of conceptions in Sweden falling in June ;
in Holland and France, in May -June ; in Spain, Austria, and Italy,
in May ; in Greece, in April. That is, the farther south, the earlier
the spring and the earlier the conceptions." Other facts of a like
kind are recorded by "Westermarck, who concludes that primitive
man had an innate tendency towards increased powers of reproduc-
tion at the end of spring or beginning of summer, and that this
tendency became variously modified under the influence of natural
selection in the different human races which subsequently arose.1

Finally, it may be pointed out that Westermarck's conclusion —
which seems a very probable one in view of the evidence which he
and others have collected — is in no way invalidated by the fact that
the human female experiences normally an uninterrupted succession
of diosstrous (i.e. menstrual) cycles ; for, as already shown, a similar
condition is known to exist in several at least of the lower Primates,
with which there is also evidence that in a state of nature the
breeding functions are restricted to particular seasons of the year.2

Whether the moncestrous or the polycestrous condition is the more
primitive is a question which cannot at present be decided. The
fact that polyoestrum is secondarily acquired among many animals
may perhaps be regarded as evidence that mono3strum is the more
primitive of the two conditions ; for, as already shown, there are
numerous instances of Mammals which are almost certainly
moncestrous in their wild state, but which have independently
assumed a condition of polycestrum under the more luxurious
influences of domestication. Thus, while the sheep, the sow, and
the cat are almost certainly moncestrous in a state of nature, the
domesticated breeds of these animals show a varying degree of

1 Mayo-Smith (loc. cit.) points out that sexual periodicity in civilised man is
much obscured by social influences. "One great social influence is tho time
of marriage. Marriage tends to accumulate about the social festivities of
Christmas time, and in Catholic countries especially in the period just before
Lent." He suggests that in agricultural districts the concentration about
Christmas is due to the leisure following the labours of the autumn. " In
cities the births are more evenly distributed, showing that artificial life has
overcome the influence of seasons and particular occupations."

3 That is to say that, whereas menstruation goes on at regular intervals all
the year round, the procestrous or menstrual periods are only followed during
the breeding season by oestri at which it is possible for conception to occur.
There are some indications that the sexual instinct among males is also
periodic, both in the lower Primates and in the human subject, but the
periodicity is not so marked as among females. Havelock Ellis (loc. cit.} has
discussed this question at some length, adducing evidence of a sexual rhythm
in men. See especially appendix to Ellis's work by Perry-Coste, who shows
that there may be a tendency towards rhythmic regularity in the sexual
functions as manifested especially in the recurrence of seminal emissions.

THE CESTROUS CYCLE IN THE MAMMALIA 67

polyoestrum which appears to depend largely upon the extent to
which domestication has been carried as well as upon food and the
influences of the surroundings. On the other hand, the existence
of the continuous polyoestrum in tropical climates among such
primitive Mammals as the Insectivores, and the common occurrence
of varying degrees of polyoestrum among the liodents, not only in
captivity but also in the wild state, point to the possibility that
polyoestrum may be the more primitive condition, and one which can
easily be reverted to under the influence of a favourable environment.

Hill and O'Donoghue l are of opinion that the moncestrous condi-
tion is the more primitive, basing their conclusion on what is known
of the breeding habits of the Marsupials, e.g. Dasyurus, Trich-osurux,
Phascolarctus, and Phascolomys, and Monotremes, which are the
most primitive of all Mammals, as well as on considerations relative
to the sexual functions in reptiles, and this conclusion we may
tentatively accept- as correct. It has already been mentioned that
in monoestrous animals like Dnsi/urus and the dog oestrus, if not
succeeded by pregnancy, is followed by pseudo-pregnancy, and both
these conditions are associated with the persistence of the corpus
luteum or glandular structure formed from the discharged follicle
after the expulsion of the ovum. In acquiring the polyoestrous habit
the duration of the corpus luteum has been much shortened down,
and the period of pseudo-pregnancy has almost or quite disappeared
so as to make way for a new ovulation and the associated changes
of oestrus.

The main purpose of polycestrum (to use teleological language)
is no doubt, as already remarked, to provide increased opportunity
for coition, and so to promote the fecundity of the race. But it
must be remembered that oestrus is not necessarily associated with
ovulation, and consequently the explanation just given of the
polycestrous habit is not of universal application. This is a point
which will be referred to again in dealing with ovulation. It is
of course possible, however, that the polycestrous condition, having
once been acquired, might in certain circumstances be perpetuated
in spite of its inutility.

Before concluding the present chapter it remains for me to allude
briefly to the effect of maternal influences on the oestrous cycle.
These, as pointed out by Heape, may or may not completely dis-
organise the recurrence of the sexual season. In such animals as
the dog they do not do so, because the dog is nionoestrous, and has,
as a rule, only two sexual seasons annually, so that the anoestrous
period considerably exceeds in length the period of gestation. In
large animals such as the camel, on the other hand, where the

1 Hill and O'Douoghue, loc. cit.

68 THE PHYSIOLOGY OF REPRODUCTION

gestation period extends for thirteen months, the recurrence of the
sexual season is postponed by pregnancy for a whole year. Again,
in small animals like the rat, gestation only prevents the recurrence
of oestrus, reducing the number of dioestrous cycles, but not inter-
fering with the recurrence of the sexual season. " But whenever
gestation occurs it encroaches upon, if it does not entirely absorb,
the ancestrum ; that is to say, it reduces the period during which
the generative organs would lie fallow if the sexual season were a
barren one. Thus in the case of a mare, a barren sexual season may
consist of a series of dioestrous cycles lasting for as long as six
months, in which case the ancestrum lasts six months also, after
which another sexual season begins. A reproductive sexual season,
however, results in a period of eleven months' gestation, interfering
not only with the dioestrous cycles which would have recurred if
conception had not taken place, but also absorbing practically the
whole of the anoestrum." l

The duration of the gestation period is intimately connected not
only with the size of the body,2 but also with the stage of development
at which the young are born.3 It is longest in the large terrestrial
and gigantic aquatic Mammals (Ungulata and Cetacea), \vhich live
amid favourable conditions of nourishment. With these animals the
young are so far advanced in development at the time of birth that
they are able to follow the mother about, and to a certain extent
shift for themselves. In Carnivores and Rodents the period of
pregnancy is relatively shorter, and the young are often born naked,
and with unopened eyes, and consequently are absolutely helpless
for a considerable time after birth. The gestation period is shortest
in the aplacental Mammals (Monotremata and Marsupialia), in which
the young are born at a very early stage and transferred to a pouch
formed by cutaneous folds in the vaginal region. In Monotremes
the young are hatched from eggs which, after being laid, are deposited
in the pouch.

The question as to what are the precise factors which determine
the length of the gestation period has already been referred to in the
first chapter, where it was pointed out that both the duration of
pregnancy and the time of the year at which breeding occurs are

1 Heape, loc. cit.

2 The period of gestation is 144 days in Southdown sheep and 150 in
Merinos which are larger, while the hybrid is intermediate. (Lydekker, The
tiheep and its Cousins, London, 1912.) The causes which determine the variation
in the gestation period within any one species have been investigated by
Dussogno, who found that in pigs neither the size, weight, nor predominant
sex of the litter affected the gestation period, but that it appeared to vary
with the age, vigour, and condition of the sow. (" Sulla durata della gravidanza
nelle Scrofe Yorkshires," L'Industria latticed e Zootecnica, 1915.)

3 Sedgwick, Student's Text-Book of Zoology, vol. ii., London, 1 905.

THE CESTROUS CYCLE IN THE MAMMALIA 69

necessarily controlled by natural selection, acting in the interests of
the next generation.

The effects of lactation upon the recurrence of osstrus vary widely,
and are often different among individuals belonging to the same
species. Thus, although the mare as a general rule is capable of
becoming pregnant while suckling, in some individuals the sexual
season is postponed, the mares only becoming pregnant once in two
years.

The return of menstruation during lactation in women has been
dealt with recently by Heil l and Dingwall Fordyce.2 Heil, who had
studied the conditions of two hundred nursing mothers, expresses
the belief that the occurrence of menstruation and not the condition
of amenorrhcea is the normal state during lactation, but that
menstruation is not so frequent in the later lactations as during the
earlier ones. Fordyce has reached similar conclusions, finding that
menstruation occurred during lactation in forty per cent, of the cases
in which suckling was performed, while in ninety-two per cent, of
the cases its return was within nine months of parturition, and that
menstruation during lactation was commoner with the earlier than
with the later lactations, showing that age is an important factor.

Amenorrhcea, or the absence of menstruation, may be due to
ameinia or some pathological condition. Fraenkel 3 states that it was
common in Germany during the recent war, when it resulted from
poverty of nutrition, overwork, and strain. A condition of amenorrhoea
is said to occur normally among the Esquimaux during the winter,
when it is clearly comparable to the ancestrum of animals. (See also
above, p. 60.)

The histological changes which occur in the internal generative
organs of various Mammalia during the oestrous cycle are described
at some length in the succeeding chapters.

1 Heil, "Laktation und Menstruation," Monatischr. f. Geburtsh. u. Gyna'k.,
vol. xxiv., 1906.

2 Fordyce, "An Investigation into the Complications and Disabilities of
prolonged Lactation." Being an extension of papers published in The Lancet,
Part I., 1906 ; The Brit. Ned. Jour., Part I., 1906 ; and The Brit. Jour, of
Children's Diseases, 1906. Gellhorn ("Abnormal Mammary Secretion," Jour.
Amer. Med. Assoc., 21st November 1908) mentions a case of an ape (Cercopitkecus)
in which menstruation always disappeared during profuse lactation, but
reappeared as soon as the mammary secretion ceased or became markedly
decreased.

3 Fraenkel, " Eierstockstatigkeit und Kriegsamenorrhoe," Zent. f. Gyn.,
Jahrgang xli., 1917.

THE CHANGES THAT OCCUR IN THE NON
PREGNANT UTERUS DURING THE CESTROUS
CYCLE

" Menstruation is like the red flag outside an auction sale ; it shows that
something is going on inside." — MATTHEWS DUNCAN.

FOR full descriptions of the morphology of the uterus in the different
mammalian orders, reference may be made to the text-books on
human, comparative, and veterinary anatomy. But before passing

FIG. 2. — Transvei-se section through Fallopian tube, showing folded
epithelium and muscular coat.

on to describe the changes which occur in the histology of the uterus
during the menstrual cycle, it may not be out of place to remind the
reader of the general structural relations of the generative organs in
the human female.

The two ovaries, the structure of which is described in the next
chapter, are situated one on each side of the pelvis, and are connected

70

CHANGES IN NON-PREGNANT UTERUS 71

with the posterior layer of the broad ligament of the uterus. In
connection with each ovary is a% Fallopian tube or oviduct, which
opens into the peritoneal cavity about an inch from the ovary.1
Surrounding the orifice is a fringe of irregular processes or fimbriae,
which, when expanded, assist in directing the ovum in its passage
into the tube. The tubes are about four inches long, and terminate
at the superior angles of the uterus, with the cavity of which they

FIG. 3. — Reproductive organs of ewe, showing ovaries, Fallopian tubes,
uterus, vagina, and broad ligament. The tubes at ovulation bend back
towards the ovaries, and do not open outwards as represented in the
figure. One of the cornua utei'i and part of the corpus uteri are
opened and show the cotyledonary papillae. (L. F. Messel.)

are in continuation. They are surrounded by an external serous
coat derived from the peritoneum, a muscular coat containing both
longitudinal and circular fibres, and an internal mucous membrane,
which is highly vascular and is lined within by a ciliated epithelium.

1 A vestigial structure lying transversely between the ovary and the
Fallopian tube on either side is called the parovariurn or epoophoron, or
organ of Rosenmiiller, or sometimes the duct of Gartner. It consists of a
few scattered tubules, with no aperture. It is the homologue of the epididyruis
of the male. Vestiges of a structure corresponding to the organ of Giraldes are
also sometimes found in the vicinity of the parovarium, but nearer to the
uterus. These have been called the paroophoron.

72 THE PHYSIOLOGY OF REPRODUCTION

Moreaux1 has investigated the changes undergone in the
Fallopian tube of the rabbit. He finds that the epithelial cells
discharge a mucous secretion during heat. The discharged eggs
become surrounded by a thick mucous envelope. During the periods
of rest the cells are inactive.

The human uterus consists of two parts, the corpus or body of
the uterus, and the cervix or neck, which opens into the vagina.

FIG. 4. — Section of a cornu of a rabbit's uterus (diagrammatic).

s, Serous layer ; Im, longitudinal muscle fibres ; cm, circular muscle fibres ; or,
areolar tissue with large blood-vessels ; mm, muscularis mucosse ; in, mucosa.
(From Schafer.)

The body of the uterus contains the following layers, which correspond
with those of the Fallopian tubes : (1) A serous layer ; (2) a thick
muscular layer, consisting of two (some say three) more or less
blended sub-layers ; and (.'>) a still thicker layer, known as the
mucous membrane or mucosa (sometimes called the endometrium),
which is composed of a connective tissue containing spindle-shaped
cells, and is lined by a ciliated epithelium bounding the uterine
cavity. The mucosa contains numerous tubular glands, which open

1 Moreaux, " Recherches sur la Morphologic et la Fonction Glandulaire de
1'Epithelium de la Trompe uterine chez les Mammifferes," Arch. cPAnat. Mic.,
vol. xiv.

CHANGES IN NON-PREGNANT UTERUS

73

out into the cavity of the uterus and are covered by an epithelial
layer, these being continuous with the epithelium of the surface.1
The sub-epithelial mucosa, which is sometimes called the uterine
stroma, contains also a number of blood-vessels and lymph spaces.
The vessels are branches of the ovarian and uterine arteries and
veins. The uterus is also supplied by nerves which are referred to
in a future chapter (p. 561).

In many of the lower Mammals the uterus is represented by two
tubes, called the horns of the uterus or uterine cornua, which may
unite posteriorly to form the corpus, or may, on the other hand, open
separately into the vagina. The arrangement of the different layers
in each of the cornua is essentially similar to that presented by the
corpus uteri in the human species.

FIG. 5. — Cross-section through cervical canal of human uterus.
(From Williams' Obstetrics. Appleton & Co.)

The neck or cervix uteri, which is narrower than the rest of the
organ, opens into the vagina by a transverse aperture known as the
os. The vagina is the broad passage from the uterus to the exterior.
Its walls contain both longitudinally and circularly arranged muscle
fibres. Internally it is lined by a stratified scaly epithelium,
surrounded by erectile tissue. The entrance to the vagina from the
exterior is guarded by a thin fold of mucous membrane, which
usually becomes perforated at the first coition. This structure, which
is called the hymen, is peculiar to the human race.2

1 With regard to the function of the glands it is clear that in their condition
of greatest development (if not at other times) this is secretory in character.
Witness the secretion of "uterine milk" during pregnancy (p. 432), and their
comparable condition in pseudo-pregnancy. Arthur Thomson, however, has
expressed the opinion that they are absorbent, and as evidence of this refers
to the supposed effects of the male ejaculate (seminal fluid) upon the female
(e.g. in promoting enlargement of thyroid). See lecture in Brit. Med. Jour.,
7th January 1922, "On Problems involved in the Congress of the Sexes in Man."

2 The significance or function of the hymen is not certainly known.
Metchnikoff (The Nature of Man, English Edition, London, 1903) suggests

74 THE PHYSIOLOGY OF REPRODUCTION

The vulva comprises the female generative organs which are
visible externally. These include the mons veneris, the labia major
and minora, and the clitoris. The last-mentioned structure is a
small erectile organ, which is homologous with the penis.1 (See
Chapter VII., p. 261.)

In giving an account of the changes which take place in the
uterus during the menstrual cycle of the human female, it will be
convenient to adopt the scheme of classification employed by Milnes
Marshall 2 in his work on " Vertebrate Embryology." This classifica-
tion, as will be seen later, is identical with that adopted by Heape 3 in
describing the menstrual changes of monkeys. The cycle is divided
into four stages, as follows : —

(1) The Constructive Stage.

(2) The Destructive Stage.

(3) The Stage of Repair.

(4) The Stage of Quiescence.

The last stage may conveniently be considered first.

The Stage of Quiescence. — The normal condition of the human
endometrium has been described by Webster,4 to whose account
the reader is referred. This author calls special attention to the
following points : (1) The thickness of the inucosa is not uniform,
but varies considerably. (2) The epithelial cells which line the
mucosa, and also those which line the glands, show differences in
shape and size, and in the position of the nuclei. (3) The epithelial
cells lining the glands are, as a rule, larger than the superficial
cells. (4) The interglandular connective tissue or stroma is mainly
embryonic in nature, and consists of a nucleated protoplasmic
reticulum, containing every stage of transformation into the more
differentiated spindle-shaped cells. (5) The stroma nearest the

that it may have been useful in the earlier history of the race, when sexual
intercourse probably occurred at an early age, before the reproductive organs
were mature. Under such circumstances the hymen, instead of being a
barrier, may have facilitated successful coitus. Metchnikoff supposes the
aperture to have become gradually dilated by repeated intercourse without
being torn, until it admitted of the entrance of the adult male organ.

1 The triangular space above the orifice of the vagina into which the
female urethra opens is often called the vestibule.

2 Milnes Marshall, Vertebrate Embryology, London, 1893.

3 Heape, "The Menstruation of Semnopithecus, etc.," Phil. Trans., B.,
vol. clxxxv., 1894, and vol. clxxxviii., 1897. A similar classification has been
adopted by Minot (Human Embryology, 1892), who divides the menstrual
process into (1) Tumefaction ; (2) Menstruation ; and (3) Restoration of the
mucosa.

4 Webster, Human Placentation, Chicago, 1901.

CHANGES IN NON-PREGNANT UTERUS

75

surface is for the most part arranged parallel to it, the cells
immediately below the epithelium forming a kind of basement-
membrane. (6) The superficial portion of the mucosa is supplied
only by capillaries. (7) The line of junction of mucosa and

a

FIG. 6. — Section through wall of vagina (upper part) of monkey.

a, Epithelium ; b, sub-mucous layer ; c, lymphatic gland ; d, nerve ;
e, Pacinian body ; /, fat cells.

muscle-wall is irregular, and there is no special muscularis mucosa?.
Whether the human uterus is really ever in a state of rest is open
to question, since there is no ancestrum, and the constructive stage
follows very rapidly if not immediately upon the stage of repair.

The Constructive Stage. — During this stage the stroma of the
uterus undergoes a process of growth. This is brought about partly

76 THE PHYSIOLOGY OF REPRODUCTION

by cell division, partly (according to Engelmann a) by an increase
in intercellular substance, and partly by an enlargement of the
glands and blood-vessels. According to Lipes,2 this stage commences
as soon as the process of regeneration (following the preceding

cv-::-; >•*;••: N-viV;. x; -.:;••••;. v^:-V :-•- ^ „•••:•'•':., "••.-. •

::f;>y;;,:>:;:;r;;^:-::?v:'^-voV' ' "-'•"•- r. :V\--i: ":-. ^.-i::-.-^.'--

^r^'y.'- ,.' .'T£^-:*'-. •'""'•'.' '.'.. -'. ••"V ":-v ''_ ~y-' T

FIG. 7. — Section through wall of vagina (lower part) of monkey.

a, Epithelium lining cavity ; b, sub-mucous layer ; c, muscular layer ;
rf, d', nerve ganglia ; e, artery ; /, fat cells.

menstrual period) is completed, which is about eighteen days after
the cessation of the previous flow. " During the stage of regenera-

1 Engelmann, "The Mucous Membrane of the Uterus, etc.," Amer. Jour.
Obstet., vol. viii., 1875.

2 Lipes, "A Study of the Changes occurring in the Endometrium during
the Menstrual Cycle," Albany Medical Annals, vol. xxv., 1904.

CHANGES IN NON-PREGNANT UTERUS

77

tion the cells of the stroma lay over each other rather thickly, but
now become pressed apart, particularly in the outer third of the
mucosa. The protoplasm of these cells becomes compressed, and
the projections by which they are bound together are either greatly
lengthened or completely separated." The capillaries of the mucous
membrane become congested (Fig. 8), and a serous or sanguineo-
serous exudate infiltrates into the stroma. The enlargement of the
vessels continues, but does not become very pronounced until shortly
before the stage of destruction which may be said to mark the
beginning of menstruation proper.

FIG. 8. — Section through mucosa of human uterus, showing pre-menstrual
congestion. (From Sellheim.)

Lipes also describes an increase in the size of the glands, of the
mucous membrane, which he supposes to be due to the collection of
the secretion of the gland-cells. This mucus-like product of the
gland-cells is said to give them a distinctly granular appearance.
" The gland-cells become uniformly swollen and take stains more
evenly, and their nuclei are more widely separated as a result of
the increase in the volume of the protoplasm, and are uniformly
more round in comparison with the oval nuclei, which are seen in
the regeneration period." Westphalen1 has pointed out that the
nuclei, which are situated near the base of the cell as a rule,

1 Westphalen, "Zur Physiologic des Menstruation," Arch, f, (jfynak., vol.
lii., 1896.

78 THE PHYSIOLOGY OF REPRODUCTION

appear in the middle of the cell at the beginning of the stage
of pre-menstrual swelling.

As a consequence of these changes the mucosa becomes consider-
ably increased in thickness. Thus, if a woman who had been
menstruating regularly dies shortly before the expected approach
of a menstrual period, the thickness of the mucous membrane is
often as much as one-sixth of an inch at its thickest part, as
compared with a thickness of from one-tenth to one-twentieth of
an inch in women who died within ten days after the cessation of
the flow.1 Leopold2 has described a growth so considerable that
the uterine cavity, prior to the stage of bleeding, becomes almost
completely obliterated.

It should be mentioned, however, that according to some authors
the amount of pre-menstrual growth in the uterine mucosa is very
slight, while Oliver3 seems to be doubtful whether any growth
occurs at all, stating that he has made an examination of uteri at
various pre-menstrual and menstrual stages, and has failed to find
any evidence of changes in the mucosa tissue apart from those
directly associated with the phenomena of bleeding. Westphalen's
view appears to be similar ; for, according to this observer, there is
no multiplication of nuclei during this stage, the pre-menstrual
swelling being brought about entirely by the serous saturation of
the stroma.

The Destructive Stage. — At the close of the constructive period
the blood leaves the capillaries and becomes extravasated freely in
the stroma, but there has been some dispute as to how this process
is effected. It has been suggested that the blood transudes through
the walls of unruptured capillaries under the influence of congestion,
or that permanent openings exist from the vessels into the uterine
glands, these being closed normally by muscular contraction ; 4 but
the belief now generally held is that, whereas the walls of many of
the congested vessels break down under pressiire, and so freely
admit of the exit of the blood corpuscles into the mucosa tissue,
haemorrhage also takes place partly by diapedesis. Engelmann,5
Williams,6 and others have ascribed the breaking down of the vessel-
walls to fatty degeneration, but this has been denied by Moricke,7

1 Galabin, A Manual of Midwifery, 6th Edition, London, 1904.

2 Leopold, " Untersuchungen iiber Menstruation und Ovulation," Arch. f.
Gynak., vol. xxi., 1883.

3 Oliver, "Menstruation : its Nerve Origin," Jour. Anat. and Phys., vol. xxi.,
1887.

1 Galabin, loc. tit. :> Engelmann, loc. cit.

6 Williams (Sir J.), "The Mucous Membrane of the Body of the Uterus,"
Obstet. Jour. Gt. Britain, vols. iii. and v., 1875, 1877.

7 Moricke, "Die Uterusschleimhaut in der verschiedenen Altersperioden
und zur Zeit der Menstruation," Zeitsch. f. Geburtshiilfe u. Gynak., vol. vii., 1882.

CHANGES IN NON-PREGNANT UTERUS

79

and more recently by Findley,1 while Leopold has described the
appearance of the fatty degeneration as a result rather than a cause
of htemorrhage.

After the extravasation of blood, the corpuscles tend to become
aggregated in lacunae which lie beneath the superficial epithelium.
These lacunse are the sub-epithelial Imematomata of Gebhard,2
according to whom the epithelium becomes lifted almost bodily from
its bed, the space between it and the stroma being filled with blood.
Gebhard concludes that the blood eventually reaches the uterine

FIG. 9. — Section through mucosa of human uterus, showing extravasation
of blood. (From Sellheim.)

cavity by being forced between the epithelial cells, or that a larger
exit is provided by certain of the cells being carried bodily away.
Gebhard also believes that bleeding may take place into the lumina
of the glands. Christ 3 states that when the menstrual now is very
profuse there is a considerable loss of surface epithelium, but that in
other cases the removal of epithelium is slight. This author has
also described bleeding into the glands. (Fig. 10.)

1 Findley, "Anatomy of the Menstruating Uterus," Amer. Jour. Obstet.,
vol. xlv., 1902.

2 Gebhard, " Ueber das Verhalten der Uterusschleimhaut bei der Menstrua-
tion," Verhand. d. Gesells. f. Geb. u. Gyn. zu Berlin, Zeitsch. f. G'eb. u. Gyn.,
vol. xxxii., 1895.

3 Christ, "Das Verhalten der Uterusschleimhaut wahrend der Menstrua-
tion," Inorg. Dissert., Giessen, 1892.

8o THE PHYSIOLOGY OF REPRODUCTION

Very contradictory statements have been made regarding the
extent to which denudation takes place during menstruation.
Williams (Sir J.), von Kahlden.1 and others among the older writers,
expressed the belief that a large part, if not the whole, of the
uterine mucous membrane was destroyed. This view, as will be
seen later, has been partially confirmed for monkeys by Heape. It
has been pointed out, however, by Whitridge Williams,2 that the
okler writers made their observations upon uteri which had under-
gone post-mortem changes. The preponderance of recent opinion
appears to be that destruction of the mucous membrane is, as a rule,
confined to the epithelium, and that this is only partially removed.
Among those who have accumulated evidence in support of this
conclusion are Gebhard, Strassmann,3 Westphalen, Findley, Whitridge
Williams, and Lipes. De Sinety,4 Moricke, and Oliver appear to
uphold the opinion that even the superficial epithelium remains
practically intact. Mahdl,6 Maerdervort,6 and also Champneys 7 have
made the exceedingly likely suggestion that the extent to which the
mucosa is destroyed varies within wide limits in different individuals
or even in the same individuals at different periods of life.
" Exfoliation dysmenorrhoea " (see p. 61) is probably a condition caused
by a more extensive denudation of the superficial layers of the
mucosa than occurs usually during menstruation.8 Oliver, who
maintains that menstruation is essentially a secretory process, states
that in cases of chronic inversion of the uterus there is no denudation
of epithelium during menstruation.9

Minot10 and Martin,11 agree in supposing that the superficial
layers of the mucosa degenerate after the blood has passed out, so
that the bleeding is in no sense the consequence of the destruction.
According to Martin, fatty degeneration plays a distinct part in
causing the destruction.

Lipes has shown that the amount of destruction is related to the

1 Von Kahlden, "Ueber das Verhalten der Uterusschleimhaut wahrend
und nach der Menstruation," Hegar's Festschrift, Stuttgart, 1889.

2 Whitridge Williams, Obstetrics, London and New York, 1904.

3 Strassmann, "Beitrage zur Lehre von der Ovulation, Menstruation, und
Conception," Arch. f. (lynak., vol. lii., 1896.

4 De Sinety, " Recherches sur la muqueuse uterine pendant la menstruation,"
Annales de (jynwc., 1881.

5 Mandl, "Beitrag zur Frage des Verhaltens der Uterusmucosa wahrend
der Menstruation," Arch. f. Qynftk., vol. Hi., 1896.

6 Maerdervort, " Die uormale und rnenstruirende Gebarmutterschleimhaut,"
Inorg. Dissert., Freiburg, 1895.

7 Champneys, "On Painful Menstruation," Harvcian Lectures, 1890.

8 Blair Bell, The Principles of Gynaecology, London, 1910.

!) Oliver, New York Ned. Jour., August 1906, June 1907, and November 1920.

10 Minot, loc. cit.

11 Martin, "The Physiology of Ovulation, Menstruation, and Fertilisation,"
Hirst's Obstetrics, vol. i., 1888.

CHANGES IN NON-PREGNANT UTERUS

81

character of the haemorrhage. If the congestion is rapid and the
amount of extravasated blood large, the denudation is comparatively
extensive ; but if the haemorrhage is slight, and takes place chiefly
by diapedesis, then the loss of tissue is practically nil. Lipes adds
that in none of the cases examined by him were there enough
epithelial cells in the discharge to suggest a complete loss of
epithelium.

Galabin states that in addition to uterine and vaginal epithelial
cells being found in the discharge, shreds of tissue can frequently be
detected showing the structure of uterine stroma. Heape x also has

FIG. 10. — Section through mucosa of human uterus, showing sub-epithelial
hsematomata *. (From Sellheim.)

detected stroma tissue in the menstrual discharge of the human
female. This clearly shows that destruction is not always confined
to the epithelial layer.

The blood poured out into the uterine cavity, and thence to the
exterior, does not usually clot, unless the amount be excessive. This
is probably due to the absence of fibrin ferment, and perhaps also
to the fact that the blood is considerably diluted with mucus derived
from the uterine glands. The glandular activity is accompanied by
an emigration of leucocytes which, according to Blair Bell,2 are
engaged in excreting calcium compounds (see p. 63). The relative

1 Heape, "The Menstruation and Ovulation of Monkeys and the Human
Female," Tram. Obstet. Soc., vol. xl., 1899.

2 Blair Bell, " Menstruation and its Relation to the Calcium Metabolism,"
Proc. Rot/. Soc. Med., July 1908.

82

THE PHYSIOLOGY OF REPRODUCTION

proportion of blood to mucus in the fluid is usually said to increase
from the commencement of menstruation, until the discharge reaches
its maximum, after which it goes on diminishing until the flow ceases.
Oliver1 has made a quantitative examination of the menstrual fluid
obtained from a girl with an imperforate hymen. After making an
incision he withdrew 70 ox.: 87'18 per cent, was water; of the
remainder 4*98 per cent, was ash and 95'02 organic material, including
12'49 serum albumen, 16'56 globulin, 3'37 mucin, and a trace of fat.
The ash contained sodium, potassium, calcium, phosphorus, and iron ;
and the salts, chlorides, carbonates, phosphates, and sulphates.

The Stage of Repair. — This corresponds to Gebhard's period of

:-V~V»

FIG. 11. — Section through mucosa of menstruating human uterus, 'showing
bleeding into the cavity *. (From Sellheim.)

post-menstrual involution. After the flow has ceased, or even a
short time before it has quite ceased, regeneration of the uterine
mucosa begins. According to Westphalen,2 profuse karyokinesis
takes place in the tissue of the mucosa, which once more increases in
thickness, whereas Heape, as will be seen later, describes a shrinkage
as occurring in the regenerative stage in monkeys. Wyder,3 who
believed in the partial destruction of the uterine stroma, concluded
that this was restored by a hyperplasia of cells in the interglandular
tissue of the deeper layers of the mucous membrane, and that the
lost epithelium was regenerated from the epithelium of the glands.
Similar views have been held by other writers.

Those authorities who hold that the destruction is practically

1 Oliver, "New Aspects of Menstruation," New York Med. Joui'., November
1920.

* Westphalen, loc. cit.

3 Whitridge Williams, loc. cit.

CHANGES IN NON-PREGNANT UTERUS 83

confined to the epithelium believe that the lost cells are replaced by
multiplication of the remaining cells. Mandl, for example, describes
various stages of mitotic division in the cells of the epithelium at
this stage. But this author is of opinion that the epithelia of the
glands assist in the process of renewal. Gebhard describes the
epithelium, which had been lifted from its bed by the blood in the
hrematomata, as sinking back to its former position, such cells as
were lost being regenerated by multiplication of the others.

The restoration of the mucosa is accompanied by a decrease in
the size of the blood-vessels, and an absorption of the blood which

FIG. 12. — Section through the human uterus during the recuperation stage.

(From Sellheim.)

remains extravasated in the stroma. As to how the blood is
absorbed has not been determined in the human female. This is a
question which will be discussed in considering the regeneration stage
in monkeys and in the lower Mammals. It is stated that new
capillaries are formed after the close of the destruction.1

It has already been mentioned that, according to Lipes,2 the
constructive stage commences as soon as repair is completed. There
is undoubtedly glandular development which may possibly be
comparable to what occurs during the post-o3strous or pseudo-

1 Geist, " Untersuchungen iiber die Histologie der Uterusschleimhaut,"
Arch. f. Mikr. Anat., vol. Ixxxi., 1913. See also Coryllos, Reviie de Gyncecol.,
vol. xviii. and vol. xxvii.

2 Lipes, loc. cit.

84 THE PHYSIOLOGY OF REPRODUCTION

pregnant period in the bitch (see below, p. 98). In this connection
it is interesting to note that, according to Hitschmann and Adler,1
the pre-menstrual uterus in man undergoes changes which are
similar in character to those observed in the pregnant uterus. It
seems possible, therefore, to regard menstruation in man as
representing pseudo-pregnant destruction (see pp. 107 and 156) as
well as prooestrous degeneration, the two series of changes being
here telescoped into one month.2

The average length of the normal menstrual cycle, as already
mentioned, is twenty-eight days. Of these about five are occupied
by the pre-menstrual swelling, four by menstruation, and probably
about seven by the regeneration process, leaving not more than
twelve days for the period of quiescence.3 There can be no doubt,
however, that the length of the respective stages must vary according
to the extent of the destruction and the amount of tissue which it
is necessary to replace. According to Westphalen,4 the regenerative
process may last for as long as eighteen days, or until the commence-
ment of the succeeding pre-menstrual swelling.5

THE CYCLE IN MONKEYS

The histology of the menstrual cycle in Semiiopithecus entellus
and Macacus rhesus has been very fully studied by Heape.6 Pre-
viously to Heape's work, Bland Sutton 7 had paid some attention to
the histology of the menstrual process in Macacus rhesiis, but without
entering into great detail. More recently van Herwerden 8 has
given an account of the cyclical changes of the uterus in Cercocebus
cynomolgus.

Heape has divided the cycle into the following four periods and
eight stages : —

1 Hitschmann and Adler, "Der Bau der Uterusschleimhaut des Geschlechts-
reifen Weibes," Nonatschr. f. Geb. u. Gyncik., vol. xxvii., 1908.

2 Marshall and Hainan, "On the Post-CEstrous Changes occurring in the
Generative Organs and Mammary Glands of the Non-Pregnant Dog," Proc.
Roy. Soc., B., vol. Ixxxix., 1917.

3 Whitridge Williams, loc. tit.

4 Westphalen, loc. tit.

5 For further references to the subject of menstruation in the human •
female the following authors may be consulted : Steinhaus, Menstruation
and Ovulation, Leipzig, 1890 ; Heape, Phil. Trans., B., vols. clxxxv. and
clxxxviii., 1894 and 1897 ; Gebhard, " Die Menstruation," Veifs Handbtu-h
der Gyndk., vol. iii., 1898. For an account of the various pathological changes
which are known to occur in the human uterus, see Macgregor, A Contribution
to the Pathology of the Endometrium, Edinburgh, 1905.

6 Heape, loc. tit.

7 Bland Sutton, "Menstruation in Monkeys," Brit, Gynvec. Jour., vol. ii.,
1880.

8 Van Herwerden, " Bijdrage tot de Kennis van den Menstrueelen Cyclus,"
Tijdschrift. d. Ned. Dierk. Vereen., vol. x., 1906.

CHANGES IN NON-PREGNANT UTERUS 85

A. Period of Rest. Stage I. The Resting Stage.

j T> • j * rt ( II- The Growth of Stroma.

B. Period of Growth. | » m The Increage of Vessels

/ „ IV. The Breaking Down of Vessels.

rt T> • j c T-V i.- V. The Formation of Lacunae.

C. Period of Degeneration.^ » VI The Rupture of ^^

\ „ VII. The Formation of the Menstrual Clot.

D. Period of Recuperation. „ VIII. The Recuperation Stage.

Heape's account may now be briefly summarised.

I. The Resting Stage. — The epitbelial layer of the uterine mucosa
consists of a single row of cubical or columnar cells. The outer
border is clearly defined, but on the inner side the protoplasm of
the epithelium is continuous with that of the sub-epithelial mucosa
or stronia tissue. The surface epithelium is continuous with that"
of the glands, but the latter rest on a basement-membrane which
separates them from the interglandular stroma. The stroma contains
round nuclei embedded in a network of protoplasm, with fine, delicate
processes in which granules may be seen. In Semnopithecus fibrils
running fan-wise were observed in the deeper parts of the stroma,
but these were not seen in Macacus. Multiplication of cells was not
noticed at this stage, either in the epithelium or in the stroma. The
vessels in the mucosa are small. A few arteries occur in the deeper
portion, but only thin-walled capillaries in the more superficial part ;
the latter, however, are fairly numerous.

II. The Growth of Stroma. — The nuclei of the more superficial
part of the stroma undergo a great increase, the division being
amitotic in character, at least so far as could be seen. As a con-
sequence the mucosa in its upper third becomes considerably swelled
(hyperplasia), but in the deeper portion there is no change in the
tissue. Owing to the effects of pressure the nuclei become elongated
or fusiform. Division occurs either by fragmentation or by the
nucleus simply splitting into two. The growth in the upper part
of the stroma is associated with an increase in the size of the blood-
vessels in the deeper part. The superficial epithelium, and also the
epithelium of the glands, remain practically unchanged.

III. The Increase of Vessels. — Owing to the continued swelling of
the stroma the nuclei in the superficial portion are packed less
densely, the lining epithelium becoming simultaneously stretched.
The glands tend to become wider. Hyperplasia of the vessels occurs
below the epithelium, the surface of the mucosa appearing flushed.
At the same time leucocytes become more numerous within the
vessels. There is no change in the constitution of the deeper portion
of the stroma.

IV. The Breaking Down of Vessels. — The whole of the mucosa,

86 THE PHYSIOLOGY OF REPRODUCTION

including the epithelium, strorria, and vessel- walls, undergoes pro-
nounced hypertrophy, and in the superficial region the congested
capillaries break down and their contents become extravasated
through the stroma. Fatty degeneration was not observed by Heape,
who is disposed to think that the degeneration is of the amyloid or
hyaline type. The leucocytes were noticed to be increased decidedly
in number, but they were only detected outside of the blood-vessels
in the superficial stroma, where the vessel-walls had given way.
Diapedesis of corpuscles was nowhere observed. The nuclei of the
stroma become larger and more rounded, and exhibit a nuclear
network and deeply staining nucleoli. The glands increase in size,
becoming longer ; their lumina are wide, and. an active process of
"secretion is taking place. Superficially the mucosa appears very
markedly flushed.

V. The Formation of Lacunce. — At this stage the extravasated
blood corpuscles collect in lacunae which are situated in the loose
stroma tissue which lies below the epithelium. These lacunae are
clearly identical with the sub-epithelial heematomata of Gebhard.
The dense stroma tissue, characteristic of an early stage, still persists
in places, but is now of rare occurrence. All the superficial vessels
have by this time broken down, but those in the deeper tissue
remain intact. Neither leucocytes nor red corpuscles are to be
found free in the deeper tissue of the stroma. The condition of the
glands is the same as in the preceding stage, but there is evidence
of degenerative changes in certain of the stroma nuclei, and also in
some of the free leucocytes.

VI. The Rupture of Lacunce. — The superficial stroma and epi-
thelium shrivel up at this stage, and, as a consequence, the blood
contained in the lacunas is poured into the uterine cavity. The
lacunae are very often close to the glands, so that when a lacuna
ruptures, a whole gland may be carried away in the blood-stream.
The lacunae have no regular inner wall, but in some places the
processes of the stroma were observed to combyie together to form
a kind of wall which appeared to resist the further encroachment
of blood corpuscles in the stroma tissue. Leucocytes are very
numerous (usually in the close neighbourhood of the ruptured vessels),
some of them being described as mononuclear, and some as having
two, three, or four nuclei (products of division). The proportion of
leucocytes to red corpuscles was found to be 2 per cent, of the former
to 98 per cent, of the latter in unruptured vessels full of blood, while
in ruptured vessels, from which blood had escaped, the percentage of
leucocytes was noted to be as high as 18*75. Heape does not state,
however, that basophil or eosinophil cells occur, such as have been

CHANGES IN NON-PREGNANT UTERUS 87

described in the uterus of the dog at a corresponding stage in the
cycle. Degenerative changes were noted in many of the epithelial
cells, and also in some of the stroma cells, certain of which were
seen scattered beneath the remains of the epithelial lining. The
stroma below the lacunte was observed to contain normal as well
as shrivelled tissue, but the deeper parts appeared to undergo very
little alteration.

VII. The Formation of t/ie Menstrual Clot. — At this stage Heape
describes "a severe, devastating, periodic action." The entire
superficial epithelium, portions of the glands or even a whole gland,
and a part of the stroma, with broken-down blood-vessels and
corpuscles, are torn bodily away, " leaving behind a ragged wreck of
tissue, torn glands, ruptured vessels, jagged edges of stroma, and
masses of blood corpuscles, which it would seem hardly possible to
heal satisfactorily without the aid of surgical treatment." Heape is
in no doubt as to the extent of the denudation, differing thus from
those writers referred to above, who believe that the destructive
process in the human female does not extend beyond certain portions
of the superficial epithelium. The cast-off mucous membrane is
termed by Heape the mucosa menstrualis. The deeper tissue under-
goes no change, the blood-vessels therein being still possessed of
complete walls, but these are larger and more numerous than before.
There is no extravasated blood in this region. The proportion of
leucocytes in the vessels was observed to be about three per cent,
of the corpuscles present, while those on the surface were estimated
to comprise about 2'5 per cent, of the total number of corpuscles.
Heape ascribes this comparative equalisation to the fact that the
ruptured vessels to which the leucocytes adhered in the earlier
stages, are themselves cast off, and their contents mingled with the
extravasated blood. The supply of leucocytes in the vessels, however,
is well maintained.

The menstrual discharge is described as consisting of (1) a viscid,
stringy, opaque white fluid derived partly from the blood-serum and
partly from the secretion of the uterine glands, containing numerous
small granules which have their origin in the broken-down plasmodium
of the uterine mucosa ; (2) red blood corpuscles ; (3) masses of stroma
tissue and epithelium, both from the lining of the uterine cavity and
from the glands, and squamous epithelium from the vagina ; and (4)
leucocytes together with isolated nuclei of broken-down epithelial
and stroma cells. The menstrual clot is composed very similarly,
containing a mass of corpuscles together with fragments of uterine
tissue. It is expelled at the end of menstruation after remaining
some time in the uterine cavity.

88 THE PHYSIOLOGY OF REPRODUCTION

VIII. The. Recuperation Stage. — The changes which occur during
this stage are described by Heape as consisting of five processes, as
follows : —

(1) The re-formation of the epithelium.

(2) The reduction of the blood supply.

(3) The formation of new and recuperation of old

blood-vessels.

(4) The changes which take place in the stroma.

(5) The behaviour of the leucocytes.

(1) The new epithelium is formed, according to Heape, partly
from the epithelium of the glands, but partly from the underlying
stroma. The latter is described as a tissue of very primitive
characteristics, and the re-formation of the epithelium is regarded as
a specialisation of cells belonging to a layer which, in the embryo,
gave rise in the same way to similar epithelial cells (that is to say,
on this view, what takes place after menstruation is merely a
repetition of a process which occurs in the embryo). The new
epithelial cells, which are at first flattened, gradually become cubical.
Heape's account is thus completely at variance with the descriptions
of those authors who hold that in the human female the epithelium
is renewed entirely from the torn edges of the old epithelium.
Heape states that the process of re-formation commences before the
expulsion of the menstrual clot, and even before the cessation of the
flow of blood into the uterine cavity.

(2) There is still an escape of blood as long as the menstrual clot
lies within the uterine cavity, but after its expulsion the flow is
checked. Heape suggests that the contractions of the uterus which
serve to expel the clot may assist in stopping the escape of blood.
Probably, also, the growth of the new epithelium helps to stop the
haemorrhage. After the growth of the new vessels the flow of blood
entirely ceases.

(3) At the commencement of this stage many of the extravasated
blood corpuscles are seen lying in intercellular spaces in the stroma.
These corpuscles, according to Heape, are drawn again into the
circulatory system by becoming enclosed within newly formed
capillaries. Heape describes the process as follows : " The protoplasm
of the cells bounding these [blood-containing] spaces flattens out, the
nuclei of the cells becoming also flattened and elongated, and
numerous fine capillary vessels are thus formed, continuous with the
deeper parts of the mucosa with large pre-existing capillaries, and so
with the circulatory system.

" These fine capillaries exist only temporarily. When the blood
corpuscles are again drawn into the circulation, and when the mucosa

CHANGES IN NON-PREGNANT UTERUS 89

has shrunk again into its resting condition, the fine capillaries are no
longer seen; but during the time in which the reclaiming process
goes on they exist in very large numbers." It should be added
that this description of the formation of vessels in the uterine
mucosa of Semnopithecus and Macacus is in opposition to the usual
view regarding the growth of new vessels, which are ordinarily
supposed to be only capable of developing as off-shoots from pre-
existing ones.

Heape also describes a recuperation of the old blood-vessels.
The nuclei which were hypertrophied become reduced in size, and
the swollen protoplasm becomes contracted. In this way the vessels
are reduced once more to their normal size.

(4) The changes in the cells of the stroma are described as being
similar to those in the cells which form the walls of the hypertrophied
vessels, the large nuclei and swollen protoplasm giving place to
compact nuclei and fine thread-like processes of protoplasm. The
multiplication of the stroma nuclei still goes on to a limited extent,
but is not nearly, so frequent. The tissue is very open during the
early stages of recuperation, but gradually becomes drawn together.
As a result the whole stroma is reduced considerably in bulk.

(5) The extravasated leucocytes, like the red corpuscles, are said
to be returned into the circulatory system by means of the newly
formed vessels. Heape says that isolated wandering leucocytes are
very rare indeed at this stage, and he makes no mention of basophil
or eosinophil cells, such as have recently been described in the
uterus of the dog. The actual proportion of leucocytes within the
vessels is said to be greater than at any other period in the cycle,
as many as fifty per cent, having been observed in certain of the
vessels. With regard to the function of the leucocytes Heape
suggests that in cases of suppressed menstruation they might play
an important part, but that in normal menstruation " they seem
to have been induced to appear on the scene in such numbers,
unnecessarily ; the casting away of the menstrual mucosa, together
with all noxious material, and the clean healing of the wounded
surface, rendering their protective presence unnecessary." At the
same time Heape points out that the presence of the leucocytes in
the vessels is evidence of the existence therein of a noxious
substance which is not present in the surrounding tissue, and he
supposes that this irritant may be got rid of completely in the flow
of blood.

Menstruation in Macacus has also been studied by Bland Sutton,1
according to whom the sanguineous discharge is slight. Sutton

1 Bland Sutton, "Menstruation in Monkeys," Brit. Gyncec. Jour., vol. ii.,
1880.

90 THE PHYSIOLOGY OF REPRODUCTION

found no evidence of destruction of the uterine mucosa, not even
of the epithelium, but the uterus was distinctly congested, and there
was an escape of blood into the cavity. It should be noted, however,
that Sutton's investigation was upon monkeys in this country,
whereas Heape's observations relate to Indian animals, and that
in Pocock's experience,1 menstruation does not, as a rule, occur in
Macaciis rhesus in the Zoological Gardens. But it would appear also
from this author's observations that the severity of the menstrual
process in monkeys may vary within as wide limits as it is said to
do in the human female.

The changes which occur throughout the menstrual cycle in
Cercocelws cynomolgm have been studied in some detail by van
Herwerden,2 who begins by classifying the material in two groups.
In group A are included those animals in which, at the time of
killing, the uterus was relatively small and menstruation was
correspondingly slight. In group B are placed those monkeys
which, on being killed, showed comparatively large well-developed
uteri, and in which the menstrual process was characterised by
some degree of severity. Van Herwerden is of opinion that the
individuals included in the first category were animals killed during
the non-breeding season, while those belonging to group B were
specimens killed at the breeding season, when the generative organs
were in a state of greater activity.

The complete menstrual cycle in Gercocebus is divided into the
following periods and stages : —

I. Inter-menstrual period.
II. Pre.menstn,a, period -{ '; gggg^ffg?* ^^

' 1. Increasing hypereemia.

2. Rupture of capillaries.

3. Formation of lacunae.

4. Degeneration of epithelium and stroma

elements.

III. Menstrual period

5. Rupture of lacunse and tearing off of

degenerate tissue.
, 6. Beginning of regeneration.
IV. Post-menstrual period.

It will be seen from this scheme of classification that the
changes recorded by van Herwerden as occurring in the menstrual
cycle of Cerewebus are very similar to those described by Heape in
Semnopitliecus and Macacus. Both authors agree in stating that the
superficial portion of the mucosa is denuded during the destruction
period, differing thus from lUand Sutton and those writers on human
menstruation (referred to above) who maintain that the denudation

1 Pocock, "Notes upon Menstruation etc.," Proc. ZooL «S'oc., 1906.

2 Van Herwerden, foe. cit.

CHANGES IN NON-PREGNANT UTERUS 91

only involves certain portions of the superficial epithelium. Van
Herwerden states that the menstrual changes are less marked in
the region of the fundus uteri.

The chief differences between van Herwerden's account and that
of Heape are as follows : —

According to the former the stroma cells increase mitotically,
and not by simple division or fragmentation as supposed by
Heape.

The epithelium is described as being renewed from the glandular
epithelium in Cercocebus, and not in part from the subjacent stroma,
as it is said to do in Semnopithecus and Macacus.

Van Herwerden says that, so far as was observed, the walls of
new vessels were not formed during recuperation from stroma cells
as has been described by Heape.

Van Herwerden states that Cercocebus may experience oestrus
after menstruation is over. Presumably, therefore, cestrus occurs
contemporaneously with the recuperation process in the uterus.

THE CYCLE IN LEMUKS

As already mentioned, Stratz l has called attention to the pro-
cestrous changes which take place in the uterus of Tarsius spectrum,
but the process has been studied more closely by van Herwerden.2
This author describes the following changes : —

(1) There is a swelling of the glands which is closely followed
by mitotic division among a large number of the epithelial cells.
Hypertemia then sets in; but the congestion is localised to certain
places, and is not diffused over the entire mucous membrane.
Afterwards blood becomes extravasated in the stroma tissue, the
corpuscles being aggregated in the more superficial parts — that is
to say, in the vicinity of the epithelium. It was noticed that
certain corpuscles were taken up by leucocytes, and transported to
the uterine cavity. Others were carried along in close association
with epithelial cells, both from the superficial layer and from the
glands.

It would appear that destruction of the epithelium does not
occur to any extent, and that the bleeding is not severe. This would
seem to constitute the chief difference between the prooestrous
changes in Tarsius, and the corresponding changes in monkeys.

The periodicity of the sexual phenomena in Tarsius spectrum has
already been referred to.

1 Stratz, Der geschlechtsreife Saugethiereierstocl; Haag, 1898.

2 Van Herwerden, loc. dt.

92 THE PHYSIOLOGY OF REPRODUCTION

THE CYCLE IN INSECTIVORES

The changes which occur in the internal generative organs
during the cycle in Tupaia javanica, and in the aberrant Insectivore,
Galeopithecus volam, have received some slight attention.

Stratz1 has described the existence of a blood-clot and a
" menstrual " flow in Tupaia, and records the presence of de-
squamated epithelial cells in the blood-clot. Van Herwerden,2
however, states that the individuals which Stratz examined were
in the puerperal stage, and that, although Tupaia can experience
" heat " and become pregnant at this time, trustworthy conclusions
regarding the severity of the prooestrous changes cannot be drawn
from such specimens. That there was considerable bleeding van
Herwerden admits. Nothing is known about the periodicity of the
changes in Tupaia.

In Galeopithecus van Herwerden describes uterine hypenemia
during the prooestrum. In the superficial mucosa numerous highly
congested capillaries were noticed. In the later stages blood was
found extravasated in the stroma, some of it being collected in
spaces which were probably comparable to the sub-epithelial hiiemato-
mata described by Gebhard in the menstruating human female. In
the superficial epithelium spots were detected where a few of the
cells had been removed. Bleeding did not appear to be localised
to any particular area in the uterus.

Van Herwerden is certain that the changes observed could not
be ascribed to a puerperal condition, as in the case of Tupaia, but
must have been the result of a normal prooestrum. The periodicity
of the changes is unknown.

THE CYCLE IN CARNIVORES

The histological changes in the non-pregnant uterus have been
studied in the dog 3 and in the ferret.4 The periods into which the
uterine cycle is divided in the dog are as follows : —

(1) Period of rest - - Anoestrum.

(2) Period of growth and congestion - 1 T>

(3) Period of destruction - - } Procestrum.

(4) Period of recuperation ... CEstrus.

Followed by further growth and glandu- Followed by pregnancy or pseudo-
lar development, these changes being pregnancy (or, as sometimes in the

succeeded by degenerative changes. ferret, by mettestrum).

1 Stratz, loc. cit.

2 Van Herwerden, loc. cit.

3 Marshall and Jolly, "Contributions to the Physiology of Mammalian
Reproduction : Part I. The (Estrous Cycle in the Dog," Phil. Trans., B.,
vol. cxcviii., 1905. Marshall and Hainan, loc. cit.

4 Marshall, " The CEstrous Cycle in the Common Ferret," Quar. Jour. Micr.
Science, vol. xlviii., 1904.

CHANGES IN NON-PREGNANT UTERUS

93

It is seen that oestrus, or the time of desire, begins normally
about the close of the period of destruction. With the ferret it
may be very prolonged, extending until the end of the recuperation
period, or even considerably beyond it. Consequently there may be
no metcBstrum (strictly speaking) with the ferret, since the period
during which copulation can occur is liable to persist until the uterus
has reached the resting stage.

(1) Period of Rest. — The uterine mucosa in both the dog and the

: -

'$:•% ••^'fL%#u* &&•• $\^i^%-

' ^^^^^^ff^^w^^^^^p

15* <v ^#

%?'

£*<*•

FIG. 13. — Section through prooestrous uterine mucosa of dog, showing
congested vessels between the glands. (From Marshall and Jolly.)

ferret is bounded at the surface by an epithelium consisting of a
single row of columnar or cubical cells, and is continuous with that
of the glands and crypts. The latter are pits in the mucous mem-
brane. The stroma is a connective tissue, containing numerous
fusiform cells. Blood-vessels of small size are fairly common.
Leucocytes do not appear to occur in the mucosa outside of the
vessels. Pigment is not present at this stage, at least ordinarily.

(2) Period of Growth and Congestion. — The mucosa at this period
becomes slightly thickened, and tends to be more compact. This is
effected by cell divisions, but mitoses have not been observed.
Retterer,1 who has contributed a short account of the changes in

1 Eetterer, "Sur les Modifications de la Muqueuse Uterine a 1'Epoque du
But," (7. R. de la Soc. de BioL, vol. iv., 1892.

94

THE PHYSIOLOGY OF REPRODUCTION

the bitch's uterus, describes the inucosa as growing to three or
four times its normal thickness, but this observation has not been
confirmed. The growth is accompanied by enlargement and conges-
tion of the capillaries, which at the same time become more
numerous.1 The vessels in the surrounding muscular tissue also
tend to enlarge. The epithelium undergoes no material change so
far as seen. In the case of the ferret the uterine cavity is described
as becoming markedly reduced in size, while the glands are stated

polym.

x, bl.

FIG. 14. — Section through proiestrous uterine mucosa of dog. (From
Marshall and Jolly.)

ex. bl., Extravasated blood corpuscles ; polym., polymorph ; sec., cells
probably indicating secretory activity.

to undergo an appreciable swelling accompanied by an increased
secretory activity.

(3) Period of Destruction. — The walls of the stretched blood-vessels
break down, and red corpuscles, accompanied by leucocytes, become
extravasated throughout the stroma. Some of the vessels, however,
remain intact. The breaking down of vessels appears to occur fairly
uniformly throughout the stroma instead of being restricted to any
particular portion. The extravasated blood for the most part collects
immediately below the superficial epithelium, but it is not aggregated
in large lacuna-like spaces, such as Heape has described in the monkey.

1 Cf. Retterer, loc. cit. ; also KeifFer, " La Formation Glandulaire de
1'Uterus," Annales de la Soc. Medico-Chirurg. de Brabant, 1899 ; and Bonnet,
"Beitrage zur Embryologie des Hundes," Anat. Hefte, vol. xx., 1902.

CHANGES IN NON-PREGNANT UTERUS 95

These " sub-epithelial hiematomata " have been noticed especially in
the procestrous bitch. The walls of the vessels in the muscular
layers do not give way.

Eventually the extravasated blood corpuscles (or, at any rate,
the majority of them) make their way into the cavity of the uterus,
and thence to the vagina, where external bleeding is observed. This
is especially noticeable in the case of the bitch, with which, as already
mentioned, external bleeding may last for as long as ten days. The
bleeding is accompanied by an increase in the mucous secretion. At
about the same stage goblet-shaped cells are frequently observable in
the glandular epithelium, and it is suggested that these are in some
way connected with the secretory activity of the glands.

It is probable that destruction of the superficial epithelium occurs
normally to a greater or less extent both in the bitch and in the
ferret. Epithelial cells have been observed lying free in the uterine
cavity, while, in some sections, places have been noticed where the
stroma presented a raw edge, having been stripped of its epithelial
covering. In the bitch a layer of flattened stroma cells may some-
times be seen in close attachment to the epithelium during the
process of denudation. In the ferret it would appear that the
destruction may occasionally be severer, but it is thought that this
is exceptional. It has been pointed out, however, that a comparison
between the thickness of the uterine wall (and conversely the size
of the uterine cavity) in ferrets killed at the commencement of the
recuperation period and during the period of rest, is very suggestive
of a definite removal of stroma as well as of epithelium in the
process of destruction.

Polymorph leucocytes have been observed in abundance at this
stage in the bitch's uterus, both in the stroma and also in the cavity,
and large mononuclear leucocytes (hyaline corpuscles), containing
pigment derived doubtless from the extravasated blood, have also
been seen to occur. Large cells, with faintly staining nuclei of very
considerable size and conspicuous nucleoli, have been noticed at rare
intervals lying in spaces in the stroma tissue of the procestrous bitch.
The origin and significance of these cells are not known.

There is no blood-clot formed in the uterus, either in the bitch
or in the ferret.

(4) Period of Recuperation. — The new epithelium in the bitch is
first seen as a layer of flattened cells which bear a resemblance to
the cells of the stroma. Its manner of formation is an open question,
but it would seem probable that it is derived mainly, if not entirely,
from the remaining cells of the old epithelium, or from those of the
glands. It is just possible, however, that in certain places the
epithelium may be renewed from the underlying stroma tissue, as

96

THE PHYSIOLOGY OF REPRODUCTION

is said by Heape (but not by van Herwerden) to be the case in the
monkey.

During the earlier stages of recuperation a variable, and often a
large, number of red blood corpuscles remain scattered in the stroma,
chiefly in the part nearest the surface. At a later stage extravasated
corpuscles are no longer seen in any quantity, while numerous new
vessels appear to have been formed, presumably from pre-existing
vessels.

Polymorphs are no longer common in the bitch's mucosa tissue,

polym.

polym.

•*>&*&a*8&

l!r 1%1? f ^

U. v.

pig.

FIG. 15.— Section through edge of mucosa of dog during an early stage of
recuperation. (From Marshall and Jolly.)

bl. v., Blood-vessel ; ep. , epithelium in process of renewal ; pig., pigment ;
polym., polymorph.

but leucocytes of other varieties are a characteristic feature. The
following kinds have been observed: (1) Coarsely granular eosinophil
cells, with lobed nuclei. These occur in the blood in cases of
trichinosis, bronchial asthma, sarcoma, osteomalacia, skin diseases,
and other affections, but are rare under ordinary conditions. (2)
Basophil cells, with simple nuclei and containing coarse granules,
but never any pigment. The number of granules varies, and in some
of the cells is very small. These basophil ceils are evidently similar
to the mast cells of Ehrlich and the plasma cells of Unua. Mast
cells are said to be often found in inflammatory areas, and are
described as occurring in the stroma tissue of tumours in association
with plasma cells, and also in tjhe peripheral circulation in cases of

CHANGES IN NON-PREGNANT UTERUS

97

lymphatic arid myeloid leucaemia. They are especially numerous
during the recuperation period of the bitch's uterus, and it is suggested
that they must in some unknown way be functionally connected with
that process. (3) Large mononuclear leucocytes (hyaline corpuscles
or macrocytes), containing blood-pigment which gives the Prussian-
blue reaction. Since pigment formation and ingestion by leucocytes
are of frequent occurrence in the bitch's uterus at about this stage

-. s^S

\tt\

>>-

'^5

>>>;.

.Sac, '

% ,

1
-
T

i *f* ~
tk

i-r'^^K.
*>»"». - • *". \-

'^

'
J&&

•^v

•*>t* .

'•%

,»"?
SWI

ra

V.i

«

%.,'"' *"'-.^

polt/m .

"f*7'.-v

*r »Vvv!
• v, - T- **

FIG. 16. — Section through portion of mucosa of dog during the recuperation
period. (From Marshall and Jolly.)

bos., Basophil cell ; eos., eosinophil cell ; mon., mononuclear leucocyte ;
polym., polymorphs ; str., stroma cell.

it is probable that this is the fate of the great majority of the
extravasated red corpuscles. It is possible, however, as suggested
in the paper from which this account is taken, that a relatively small
proportion may make their way into the lymphatics, and so re-enter
the circulation. Pigment formation has not been observed in the
ferret.

If copulation . has taken place, spermatozoa in great numbers may
be observed in the deeper portions of the uterine glands, as well as
along the edges of the uterine cavity.

Recuperation in the bitch is succeeded either by pregnancy or
pseudo-pregnancy according to whether or not the ova discharged
4

98

THE PHYSIOLOGY OF REPRODUCTION

during oestrus are fertilised. During pseudo-pregnancy the uterus
undergoes growth changes which relate chiefly to the blood-vessels
and glands of the mucosa.1 These increase in size, the whole organ
assuming a histological appearance of great activity. Three weeks
after the beginning of proosstrous bleeding, the epithelial cells lining
the crypts and glands are columnar, and this condition remains until
about the end of the fifth week when the cells become cubical. The

FIG. 17. — Section through mucosa of dog during a late stage of recuperation.
(From Marshall and Jolly.)

bl. v., Blood-vessel ; sp., spermatozoa in cavity of gland.

lumina of the glands contain a colloidal secretion and in the later
stages remains of desquamated epithelial cells. About the eighth
or ninth week from the beginning of " heat " the capillaries begin
to break down and corpuscles are freely extravasated in the

1 Marshall and Hainan, "On the Post-CEstrous Changes occurring in the
Generative Organs and Mammary Glands of the Non-Pregnant Bog," Proc.
Ray. Soc., B., vol. Ixxxix., 1917. Cf. Keller, "Uber den Bau des Endometi'iums
beim Hunde," Anat. ffefte, vol. cxviii., 1909; and Drahn, "Die anatomischen
Veranderungen am Geschlechtsapparat unserer Haustiere bei der Bi-unst mit
besonderer Beriicksichtigung der Hundin," Liang. -Diss. zu Hannover, Berlin,
1913. This memoir contains interesting comparative data.

CHANGES IN NON-PREGNANT UTERUS

99

stroma, but apart from this circumstance the mucosa shows no
resemblance to that of the prooestrous stage, for the gland epithelium
is either broken down or else new and attenuated instead of being
columnar like that of the bitch during " heat." The complete series
of changes occurring in the pseudo-pregnant uterus are in a general

FIG. 18.— Section through uterine mucosa of bitch forty-eight days after
the end of prooestrum (retrogressive stage of pseudo-pregnancy). Many
of the glands are degenerating ; their lumina contain colloid and the
remains of desquamated epithelial cells. Extravasated blood is seen
in the stroma. (From Marshall and Hainan.)

way similar to those occurring in the pregnant condition. In the
latter the secretion coming from the glands is a source of nutriment to
the foetus (see p. 444). Decidual cells (pp. 453-5-7) are not normally
found in any of the Carnivora. The degenerative changes which
occur at the close of pseudo-pregnancy are perhaps comparable to
those taking place in the uterus in association with parturition.
The entire sequence of iiterine changes are correlated with the
contemporaneous series of ovarian changes, as pointed out below,

ioo THE PHYSIOLOGY OF REPRODUCTION

more especially in dealing with the development and retrogression
of the corpus luteum (p. 373). The mammary changes are also
correlated (p. 617).

THE CYCLE IN RODENTS

Considerable attention has recently been paid to the uterine
changes in Rodents. In the rabbit it had long ago been noticed that
the uterus is swollen and congested during "heat," and the same

FIG. 19. — Section through portion of procestrous uterine mucosa of rabbit,
showing glandular activity, with leucocytes inside gland and passing
through gland epithelium. (From Blair Bell, in Proc. Roy. Soc. Med.)

observation was made in the marmot (Spermophilus citillus).1 Lataste 2
described proo?strous growth and congestion in the uterus of several
Muridse, and this was stated to be followed by a sanguineous discharge
from the vaginal opening. Lataste also described desquamation of
the uterine epithelium, but he appears to have regarded this process
as taking place independently of " heat."

More recently Konigstein3 has recorded cyclical changes in

1 Rejsek, "Anheftung (Implantation) des Saugethieres an die Uteruswand,
insbesondere des Eies von Spermophilus citillus" Arch. f. Mikr. Anat., vol. Ixiii.,
1904.

2 Lataste, Recherches de Zoethique sur les Mammiferes de Vordre des Rongeurs,
Bordeaux, 1887.

3 Konigstein, " Die Veranderungen der Genitalschleimhaut wahrend der
Graviditat und Brnnst bei einigen Nagern," Pfliigei^s Arch., vol. cxix., 1907.

CHANGES IN NON-PREGNANT UTERUS 101

several Rodents (rat, guinea-pig, etc.), and has described procestrous
desquamation of the uterine epithelium, followed by recuperation.
The degenerative changes are accompanied by a secretion of mucus,
and there is a marked leucocytosis over the entire generative tract.
Desquamation of epithelium also occurs in the vagina. Furthermore,
emigration of leucocytes between the epithelium of the glands,
accompanied by great glandular activity, has been observed by
Blair Bell l in the prooestrous uterus of the rabbit.

FIG. 20. — Section through uterine mucosa of rabbit nine days after sterile
coition. The condition is one of pseudo-pregnancy, the glands being
very well developed. (From Hammond and Marshall.)

In the rabbit pseudo-pregnant uterine hypertrophy only occurs
usually under experimental conditions,2 as when the doe has
copulated with a buck in which the operation of vasectomy (or
severance of the vasa deferentia) has been performed so that
spermatozoa cannot be ejaculated, or where the female has had the
Fallopian tubes severed. Under such conditions the corpus luteum
(see p. 149) is formed in the ovary. The uterus undergoes growth,
vascularisation and extensive glandular development followed by

1 Blair Bell, loc. cit.

2 Ancel and Bouin, "Sur les Fonctions du Corps Jaune Gestatif," Jour.
Physiol. et Path. Gen., vols. xii. and xiii., 1910 and 1911. Hammond and
Marshall, "The Functional Correlation between the Ovaries, Uterus, and
Mammary Glands in the Rabbit," Proc. Roy. 8oc., B., vol. Ixxxvii., 1914.

102 THE PHYSIOLOGY OF REPRODUCTION

degenerative changes comparable to what occur normally in the
pseudo-pregnant bitch (p. 98). The mammary glands also develop
(p. 617) and secrete milk. The entire pseudo-pregnant period is
somewhat less in duration than true pregnancy, which in the rabbit

FIG. 21.— Section through uterine mucosa of rabbit twenty -four days after
sterile coition (retrogressive stage in pseudo-pregnancy). A great
quantity of extravasated blood is seen. The glands are still somewhat
enlarged. (From Hammond and Marshall.)

lasts thirty days. Exceptionally (as when two doe rabbits "jump"
one another and show sexual excitement), ovulation followed by
pseudo-pregnancy may take place without coition having occurred.1
In the guinea-pig Stockard and Papanicolaou 2 have described a

1 Hammond and Marshall, loc. tit.

2 Stockard and Papanicolaou, " The Existence of a Typical (Estrous Cycle in
the Guinea-Pig," Amer. Jour, of Anat., vol. xxii., 1917.

CHANGES IN NON-PREGNANT UTERUS 103

marked correlation between the cyclical uterine changes and the
developmental cycle in the corpora lutea of the ovaries (see p. 38).
During the second week after a heat period the cells of the
uterine and also the vaginal mucous membrane begin to show
signs of degeneration and the process of desquamation commences.
At the completion of two weeks the mucosa undergoes " wholesale
destruction," but it is not clear whether this is to be regarded as
prooestrous or pseudo-pregnant degeneration, or whether it is a case
of the two processes being compressed into one such as may possibly
occur in man.1

Cyclical changes in the sexual organs of the rat have also
been described by Long and Evans,2 and by Kirkham and Burr.3

THE CYCLE IN UNGULATES

The uterine changes have been worked out in the sheep and in
the sow. As described in the former4 they relate chiefly to the
blood-vessels, and are grouped according to four periods as in the
case of the monkey, the dog, and the ferret, referred to above.

(1) Period of Rest. — The histological characters of the uterus
during this period are those of an organ in a state of quiescence.
Protoplasmic processes can be seen passing from certain of the stroma
nuclei, but these, though denser in some places than in others, show
little evidence of division. Dark brown or black pigment may be
present in considerable quantities, especially in the region subjacent
to the epithelium, both in the cotyledonary papilla; and (more
frequently) between them and round their bases. Such pigment has
not been observed in yearling sheep (i.e. in sheep less than a year
old) ; neither does it appear to occur, as a rule, during the anoestrum,
but only during the dioastrous interval.

(2) Period of Growth. — The nuclei in the stroma multiply, and
the mucosa increases slightly in thickness. The epithelium, however,
appears to remain unaffected. The blood-vessels increase both in

1 Cyclical changes in the guinea-pig, more particularly in the ovary, were
previously described by Leo Loeb (" The Cyclic Changes in the Ovary of the
Guinea-Pig," Jour, of Aforph., vol. xxii., 1911). See also Ishii ("Observations
on the Sexual Cycle of the Guinea-Pig," Biol. Bull., vol. xxxviii., 1920).

2 Long and Evans, "The (Estrous Cycle in the Rat," Anat. Record, vol. xviii.,
1920.

3 Kirkham and Burr, "The Breeding Habits, Maturation of Eggs, and
Ovulation of the Albino Rat," Amer. Jour, of Anat., vol. xv., 1913. For other
work on the oestrous cycle and sexual periodicity, etc., in Rodents, see abstracts
of papers by Long and Evans as well as of papers by Freyer, Sutter, and others
in Proc. Amer. Assoc. Anat., 1920 and 1921, Anat. Record, vols. xviii. and xxi.
Long and Evans have described pseudo-pregnancy in the rat as a result of
sterile coition and of mechanical stimulation of the cervical canal.

4 Marshall, " The CEstrous Cycle and the Formation of the Corpus Luteum
in the Sheep," Phil. Trans., B., vol. cxcvi., 1903.

104 THE PHYSIOLOGY OF REPRODUCTION

size and number, producing uterine congestion. These changes occur
both in the cotyledonary papillae and in the intervening tissue
around the bases of the papilla?.

(3) Period of Destruction. — The congestion is followed in most
cases by the breaking down of some of the vessels. Very frequently
the first extravasation takes place from vessels situated immediately
below certain parts of the stroma where the nuclei are most thickly
distributed: Leucocytes are extravasated along with the red cor-
puscles, but there is no evidence of the existence of wandering cells
apart from those which are derived apparently from the broken-down
vessels. The blood tends to collect below the epithelium. Bleeding
into the uterine" cavity may occur, but is not invariable. A few
epithelial cells are sometimes torn off (presumably in places where
blood is poured out into the cavity), but destruction even to this
extent does not necessarily take place. Denudation of the stroma
has never been observed. It would seem that the severity of the
prooestrous process tends to diminish with each successive dioestrous
cycle in the breeding season, and that sometimes in a late prooestrum
the period of destruction is never reached, the congested vessels
subsiding without undergoing rupture. Bleeding, when it does
occur, appears to be more frequent in the cotyledonary papilla?
than between them, and is commoner in the large papilla? than in
the smaller ones.

Kazzander } appears to have been the first to detect extravasated
blood in the sheep's mucosa. Subsequently Bonnet2 has noted
uterine bleeding in various Ruminants, as well as in the mare and
sow, and Kolster3 has made similar observations (cf. also Emrys-
Roberts, see p. 43). Ewart also has described prooestrous extravasa-
tion and the presence of heematoidin crystals in the uterus of the
mare. Glandular activity during heat was also noted.4

(4) Period of Recuperation. — The sheep's procestrum may be said
to end with the period of destruction, the entire process probably
lasting for not longer than one or two days, its exact duration
depending upon its severity. (Estrus itself, which occurs during the
beginning of the period of recuperation, sometimes occupies only a
few hours.

In those places where bleeding into the cavity took place in the
preceding period the epithelium is renewed, apparently from the

1 Kazzander, " Uber die Pigmentation der Uterinschleimhaut des Schaf es,"
Arch. f. Mikr. Anat., vol. xxxvi., 1890.

2 Bonnet, article in Ellenberger's Vergleichende Physiologie der Haussauge-
thiere, vol. ii., Berlin, 1892. Cf. also Ellenberger's article in same volume.

3 Kolster, " Weitere Beitrage zur Kenntniss der Embryotrophe bei Indeci-
dunten," Anat. Hefte, vol. xx., 1902.

4 Ewart, " Studies on the Development of the Horse," Trans. Hoy. 8oc. Edin.,
vol. li., 1915.

CHANGES IN NON-PREGNANT UTERUS

105

edges of the adjoining epithelium which had not suffered destruction.
In this way the re-formation of the epithelium is sufficiently
accounted for, since, as already remarked, only a very inconsiderable
number of cells is removed during the sheep's proosstrum.

Congestion of the stroma gradually diminishes, and the mucosa
as a whole undergoes a slight shrinkage. It would appear that a
few new capillaries are formed, but there is no evidence that any
of the extravasated corpuscles are gathered up afresh into the
circulatory system. On the other hand, there are ample indications

pig.

FIG. 22. — Section through portion of uterine mucosa of sheep, showing black
pigment (pig.) formed from extravasated blood.

that all those corpuscles which remain in the tissue become trans-
formed into pigment, as originally concluded by Bonnet.1 According
to this investigator, the extravasation takes place in the deeper
mucosa, and the derivatives of the corpuscles are carried in the
form of pigment to the more superficial area by wandering cells.
Kazzander,2 however, does not admit the agency of leucocytes ; but
the most recent observations support Bonnet's conclusions, excepting
that (as previously stated) the extravasation which takes place
during the destruction period is in the superficial mucosa rather

1 Bonnet, " Ueber Melanose der Uterinschleimhaut, etc.," Deutsche Zeitsch.
f. Thiermedizin, vol. v., 1880, and vol. vii., 1882 ; " Beitrage zum Embryologie
der Wiederkauer, etc.," Arch. f. Anat. u. Phys., Anat. Abth., 1884.

2 Kazzander, loc. tit.

4 A

io6 THE PHYSIOLOGY OF REPRODUCTION

than in the deeper tissue. Thus, although leucocytes are probably
involved in the process of pigment formation, there is no need to
assume that they carry the extravasated corpuscles to the region
where pigment is most abundant. Sometimes the interior of the
uterus appears superficially to be perfectly black with pigment, but
in such cases the pigment is, no doubt, derived from blood which
had been extravasated during a series of procestrous periods, and
not merely during the most recent one. Assheton l states that the
pigment so formed is subsequently disposed of.

Corner2 has described cyclic changes in the uterus of the sow.
Just before oestrus there is evidence of activity on the part of the
epithelial cells in which mitotic figures may be found, while a contrary
process is manifested here and there in nuclear chromatolysis and
degenerate changes, and neutrophilic polymorph leucocytes in the
sub-epithelial stroma become very numerous. During oestrus the
stroma is very oedematous. The post-oestrous changes are very
marked. The epithelial cells actively secrete a serous fluid from the
eighth to the tenth day, after which they subside to a cuboidal form,
and there is a slow reversion to the oestrous type. Post-oestrous
glandular hypertrophy is not definite, but otherwise the changes are
clearly suggestive of an abbreviated pseudo-pregnancy occurring
under the influence of the corpus luteum of the ovary (see above,
pp. 99-101, and below, pp. 371-372).

THE CYCLE IN MAKSUPIALS

The changes which occur in the internal generative organs of
the Marsupial cat (Dasyurus viverrinus) have been described fully by
Hill and O'Donoghue (see p. 36). The prooastrum lasts for from
four to twelve days, and during this time the uterine mucosa
increases in thickness and becomes more vascular, while its glands
lengthen and become convoluted and the epithelium tends to
thicken. During oestrus, which lasts one or two days, the changes
above described are continued. Following oestrus there is, according
to these authorities, a post-oestrous period lasting five or six days
and terminated by ovulation, and during which the uterine changes
continue further. This is followed by either pregnancy or pseudo-
pregnancy. During pseudo-pregnancy the uteri enlarge considerably
and become still more vascular, and these changes are succeeded by
degeneration and desquarnation of epithelium with extravasation of

1 Assheton, " The Morphology of the Ungulate Placenta," Phil. Trans., B.,
vol. cxcviii., 1906. Changes in the uterine mucosa have also been described in
pigs. See Steyn, Oster. Wschr. f. Tierheilkunde, 1912 ; and Geist, 1913, loc. cit.

2 Corner, "Cyclic Changes in the Ovaries and Uterus of the Sow, etc."
Contributions to Embryology, No. 64, Carnegie Institute (Washington) Publica-
tions, 1921.

CHANGES IN NON-PREGNANT UTERUS 107

blood. Eventually regeneration sets in and the mucous membrane
undergoes recuperation. According to Hill and O'Donoghue the
changes which occur during pseudo-pregnancy are comparable to
those of the procestrum in the Eutheria in which animals the
cyclical events have been thrust forward to a much earlier stage
as compared with the marsupial. It has been pointed out, however,
that there is no necessity to take this view since the pseudo-
pregnant uterine phenomena of Dasyurm find their parallel in
the rabbit under experimental conditions, and normally in the
monoestrous dog l (see p. 98).

A consideration of the facts set forth in this chapter should
leave one in no doubt regarding the essential similarity between
the menstrual cycle in the Primates, and the cestrous cycle in
the lower Mammalia. Those who have denied that there is any
correspondence between " heat " and menstruation 2 have laid stress
upon the assertion that whereas " heat " in the lower animals is
the time for coition, this act, as a general rule, is not performed
during menstruation. But, as was first pointed out by Heape, it
is the prooestrum alone and not the entire " heat period " (a term
used generally to include both prooestrum and oestrus) which is the
physiological homologue of menstruation ; and, moreover, the latter
process in many of the Primates is succeeded by a regular post-
menstrual cestrus.

It is possible, however, that menstruation in man and monkeys
represents pseudo-pregnant destruction as well as prooestrous
degeneration, the complete cycle of changes being compressed into
one month, and unless some such explanation be adopted one must
suppose that the processes of pseudo-pregnancy are unrepresented
in the menstrual cycle.

Nielsen3 goes further and supposes that menstruation in man
does not represent the prooestrum at all, but corresponds to a later
phase in the cycle which must be identified with pseudo-pregnant
destruction, but the preponderating evidence is against this view.

It has been shown that although the changes which occur in the
uterus during the cycle present a general similarity in the various

1 Marshall and Hainan, loc. tit. In all these animals there are parallel
pseudo-pregnant changes in the mammary gland and in the development,
persistence, and retrogression of the corpora lutea (see below, pp. 371-373).

2 Beard, in The Span of Gestation and the Cause of Birth (Jena, 1897), says,
" very little is required in disproof " of this correspondence.

3 Nielsen, " Om Corpus Luteums Funktion og den Fysiologiske Korrelation
mellem Ovarier og Uterus," Den Kgl. Veterinaer og Landbohojskole Aarsslrift,
1921. According to this author, in the cow, sow, and the bitch, ovulation
seems to occur before or at the beginning of procestrum, but see below,
pp. 130-133. Compare Leo Loeb, Surg., Gyn., and Obstet., vol. xxv., 1917.

io8 THE PHYSIOLOGY OF REPRODUCTION

mammalian types in which they have been studied, yet there is a
considerable amount of variation in the severity and duration of
the procestrous phenomena. The extent of the congestion, and the
destruction which usually succeeds it, are greatest, as a rule, in the
highest Mammals, and comparatively slight in the Rodentia and
Ungulata.

The purpose or meaning of the prooastrum, and the factors which
contribute to its occurrence, will be considered as fully as the present
knowledge of the subject permits, after the changes which take place
in the ovaries have been dealt with, in a future chapter of this work.
It may be at once stated, however, that most authorities are now
agreed that the menstrual process is in some sense a preparation for
the attachment of an ovum to the wall of the uterus, but opinions
differ as to the precise nature of the preparation. On the other
hand, it is evident that the changes involved in menstruation are not
absolutely essential, since there are records of pregnancy occurring
in individuals who had never experienced menstruation. Moreover,
there is evidence that the prooestrous discharge may be not only of
no utility -to the organism, but may even become injurious, as in the
more severe cases of menstruation among women.

In view of these facts it may be called in question whether the
procestrous changes in the uterus should not be regarded merely as
the result of a wave of disturbance which ushers in the period of
desire, and is of the nature of a consequence rather than a purpose.
This is in accord with Metchnikoff' s suggestion,1 that the catamenia
in women are essentially a " disharmony " of organisation, which has
been brought about as the result of modifications acquired recently in
the history of the species. If this is so, a similar explanation must
be adopted in the case of those animals which experience an especially
severe prooBstrum. According to such a view as this the phenomena
of menstruation must be looked upon as belonging to -the borderland
of pathology. In this connection the large number of leucocytes
which attend the menstrual process, some of them clearly phagocytic
in function, is not altogether unsuggestive.

1 Metchnikoff, The Nature of Man, Mitchell's Translation, London, 1903.

CHAPTEK IV

CHANGES IN THE OVARY— OOGENESIS— GROWTH
OF FOLLICLES— OVULATION— FORMATION OF
CORPORA LUTEA AND ATRETIC FOLLICLES-
THE SIGNIFICANCE OF THE PROCESTROUS
CHANGES IN THE UTERUS

"The newest freak of the Fallopian tubes and their fimbrise, and the
very latest news from the ovisac and the corpora lutea." — JOHN BROWN,
Horce Subsecivce.

DEVELOPMENT OF OVARY AND OOGENESIS

THE animal egg is a large spheroidal cell consisting of external
protoplasm or cytoplasm, a nucleus or germinal vesicle, and a
nucleolus or germinal spot.1 Within the cytoplasm is a mass of

FIG. 23. — Section through ovary of cat. (Schron.)

1, Outer surface ; 1', attached border ; 2, fibrous central stroma ; 3, peripheral
stroma ; 4, blood-vessels ; 5, young follicles ; 6, 7, 8, 9, and 9', larger
developing follicles ; 10, corpus luteum.

food material or yolk (sometimes known as deutoplasm), the quantity
of which varies slightly in different Mammalia, and is very con-
siderable in birds and certain other animals. The unfertilised ovum
differs from the male germ -cell or spermatozoon in its devoting itself
mainly to the storage of food-substance and accumulation of potential

1 A centrosome has been described as present in the ova of some animals.
For a detailed description of the ovum in different forms see Wilson, The Cell
in Development and Inheritance, 2nd Edition, New York, 1900.

109

i io THE PHYSIOLOGY OF REPRODUCTION

energy, for it is incapable of active movement. The metabolic pro-
cesses of the ovum, therefore, are almost entirely constructive, while
those of the spermatozoon are largely destructive. The function of
the ovum is to conjugate with the spermatozoon, and subsequently,
by a lengthy process of cell division, to give rise to a new individual.

FIG. 24. — Section through ovary of adult dog. (From Waldeyer.)

a, Germinal epithelium ; fc, remains of egg-tubes ; c, small follicles ; d, more
advanced follicle ; e, discus proligerus and ovum ; f, second ovum (a rare
occurrence) ; g, theca externa of follicle ; /*, theca interna ; t, membrana
granulosa ; Ic, degenerate follicle ; /, blood-vessels ; m, tubes of paro-
varium ; ^, involuted germinal epithelium ; z, transition from germinal
to peritoneal epithelium.

The mammalian ovary,1 or organ in which the ova are produced,
is composed of a stroma of fibrous connective tissue, which contains
some plain muscular fibres (especially in the neighbourhood of the

1 See also Stratz, Der gcachlecktsreife Sdiigethiereierstock, Haag, 1898.

CHANGES IN THE OVARY

in

attachment to the broad ligament) as well as numerous blood-vessels.
The surface is lined by a layer of columnar epithelial cells. Within
are a number of vesicles of various sizes, each with an ovum,
surrounded by an epithelium. These are called Graafian follicles'.
Certain other structures, consisting of very large yellow-coloured
cells enclosed by a branching network of connective tissue, are also
often found. These are the corpora lutea or discharged follicles to

FIG. 25. — Section through ovary of rabbit, showing follicles and ova in
different stages of development. (L. F. Messel.)

be described more fully later. The stroma contains, further, a
varying number of epithelioid interstitial cells.

In order to gain a proper understanding of the structural and
functional relations of the different parts of the ovary, it is necessary
to make some study of its developmental history.

Piliiger l appears to have been the first to regard the ova 2 and
epithelial cells of the Graafian follicles as originating either in the
form of ingrowths simulating tubular glands, or as solid columns of
cells from that embryonic layer which Waldeyer afterwards designated'

1 Pfliiger, Ueber die Eierstocke der Saugethiere und des Menschen, Leipzig,
1867.

2 The mammalian ovum .was, discovered by von Baer (Ueber Entwicke-
lungsgeschichte der Thiere — Beobachtung und Reflexion, vol. i., Konigsberg, 1828).
In 1861 Gegenbaur showed that the vertebrate ovum was a single cell.

ii2 THE PHYSIOLOGY OF REPRODUCTION

the germinal epithelium. The tubular ingrowths had already been
noticed by Valentin,1 who, however, failed to recognise their connection
with the germinal epithelium. Later observers, however, did not
confirm the tubular origin of the ovary.

To Waldeyer belongs the credit of first recognising the true
nature and significance of the process of egg formation, an account of
which was published in his famous monograph, Eierstock und Ei?
He found that in the chick,, on the fourth day of development, the
ccelomic epithelium which covers the inner surface of the Wolffian
body became differentiated from the tissue surrounding it, the cells
being relatively large and cuboidal in shape. A little later he
observed that the cells had multiplied to such an extent as to give
rise to a distinct elevation. In this way the germinal epithelium
was formed, and this marked the site of the future ovary. The

G.E,

FIG. 26. — Section through ovary of pig embryo. (From Williams'
Obstetrics, Appleton & Co.)

G.E., Germinal epithelium ; S., stroma.

mesoblast underlying the germinal epithelium is described as growing
upwards among the cells of the latter, and so giving rise to the
appearance of those germinal ingrowths or " egg-tubes," which were
described by Pfl tiger.

The cells of the germinal epithelium are thus divided by mesoblast
into clusters of "egg-nests" which contain the primordial ova, as
Waldeyer has shown. As a result of this process two zones of tissue
are formed in the future ovary. The outer or cortical zone consists
of clusters of cells derived from the germinal epithelium, with
mesoblastic processes in between them. The inner or medullary
zone is composed at first entirely of mesoblast, which ^gives rise to
the vascular tissue and stroma of the ovary.

The majority of investigators, including Balfour,3 Schafer,4 Nagel,5

1 Valentin, "TJeber die Entwickelung der Follikel in dem Eierstocke der
Saugethiere," Miille^s Arch., 1838.

2 Waldeyer, Eierstock und Ei, Leipzig, 1870.

3 Balfour, -" Structure and Development of the Vertebrate Ovary," Quar.
Jour. Micr. Science, vol. xviii., 1878.

4 Schafer, "On the Structure of the Immature Ovarian Ovum, etc.," Proc.
Hoy. >S*oc., vol. xxx., 1880.

5 Nagel, "Das menschliche Ei," Arch. f. Mikr. Anat., vol. xxxi., 1888.

CHANGES IN THE OVARY 113

and von Winiwarter,1 have followed Waldeyer in supposing that the
follicular epithelial cells (which form the innermost layer of the wall
of the Graafian follicle) are derived like the ova from the germinal
epithelium. Schafer described appearances indicating the possibility
of the innermost layer of follicular epithelium being derived from
the ovum itself ; but, as he himself pointed out, this view does not

. -a .- 'L**±t.- a t» t*V • \S*fl '•' ^ »i

^ «=>'*''••

FIG. 27. — Cortex of pig embryo, showing germinal epithelium, Pfliiger's
tubes with ova in various stages of development. (From Williams'
Obstetrics, Appleton & Co.)

involve any morphological absurdity if the ova and follicle-cells have
a common origin. Balfour described protoplasmic masses of em-
bryonic ova in which the cells appeared to be united together in
such a way as to suggest that one ovum might undergo development
at the expense of the others. Somewhat similar appearances have
been observed in the bat's ovary by van Beneden,2 who regarded

1 Von Winiwarter, "Becherches sur 1'Ovogenese, etc.," Arch, de Biol.,
vol. xvii., 1901.

2 Van Beneden and Julin, "Observations sur la Maturation, etc.," Arch, de
Biol., vol. i., 1880.

them as syncitia from which both ova and follicular epithelial cells
took origin.

On the other hand, Kolliker believed that the follicle-cells arose
from the epithelium of the Wolffian body, while Foulis,1 Schron,2
Wendeler,3 and Clark,4 expressing the opinion that the follicle-cells
are derived from the mesoblast, have also dissented from this the
more usual view. Clark, in support of his theory, has pointed out
that the cells which immediately surround the primordial follicles
are often spindle-shaped and similar in appearance to many of the
stroma cells, and further, that the primordial ova in the early stages
of development are often apparently in direct contact with
connective tissue which obviously had been derived from the
embryonic mesoblast.

Most authorities, however (including the more recent in-
vestigators), are of opinion that the follicular epithelial cells, in
common with the ova, are derived from the germinal epithelium.
Further, Miss Lane-Claypon 5 has shown that the epithelioid
interstitial cells,6 which (in addition to the connective tissue and
plain muscle fibres) are contained in the ovarian stroma, in all
probability arise also from the original germinal epithelium. This
has been confirmed by Miss M'llroy,7 who states that the primordial

1 Foulis, "The Development of the Ova, etc.," Jour. Anat. and Phys.,
vol. xiii., 1876.

2 Schron, "Beitrag zur Kenntniss der Anatomie und Physiologie des
Eierstocks der Saugethiere," Zeitsch. f. wissensch. Zool., vol. xii., 1863.

. 3 Wendeler, "Entwickelungsgeschichte und Physiologie der Eierstocke,"
Martin's Die Krankheiten des Eierstocks und JVebeneierstocks, Leipzig, 1899.

4 Clark, "The Origin, Growth, and Fate of the Corpus Luteum," Johns
Hopkins Hospital Reports, vol. vii., 1898.

5 Lane-Claypon, " On the Origin and Life History of the Interstitial Cells
of the Ovary of the Rabbit," Proc. Roy. Soc., B., vol. Ixxvii., 1905.

6 For a comparative account of the interstitial substance in the ovaries of
various Mammals, with references to the literature, see Fraeiikel, " Vergleichende
Histologische Untersuchungen iiber das Vorkommen driisiger Formationen im
Interstitiellen Eierstocksgewebe," Arch. f. Gynak., vol. Ixxv., 1906. According
to Ancel and Bouin interstitial cells are not present in the ovaries of animals
which ovulate spontaneously, the corpus luteum taking their place. (Bouin
and Ancel, "Sur les Homologies et la Signification des Glandes a Secretion
Interne de 1'Ovaire," C. R. Soc. Biol., vol. Ixvii., 1919.) See also O'Donoghue
(" On the Corpora Lutea and the Interstitial Tissue of the Ovary .in Marsupials,"
Qitar. Jour. Micr. Science, vol. Ixi., 1916), and Cesa-Bianchi (" Osservazione sulla
struttura e sulla funzione della cosidetto glandiola interstiziale dell' ovaia,"
Arch. d. Fis., vol. iv., 1907). The latter author says that there is an inverse
relation between the size of the corpus luteum and the development of the
interstitial cells in1 the various species of Mammals ; also that in hibernating
animals the interstitial cells are poorly developed during the winter sleep, but
during summer and particularly at the time of sexual activity they are very
numerous. (See p. 331.) See also Athias, "Recherches sur les Cellules Inter-
stitielles de 1'Ovarie des Cheiropteres," Arch, de Biol., vol. xxx., 1919 ; and
Rasmussen, "Cyclic Changes in the Interstitial Cells, etc.," Endocrinology,
vol. ii., 1918. See also footnote, p. 120.

7 M'llroy, " The Development of the Germ-Cells in the Mammalian Ovary,"
Proc. Roy. Soc. Edin., vol. xxxi., 1910.

CHANGES IN THE OVARY 115

germ-cells or oogonia give rise, after a series of two or more divisions,
to ova, follicle-cells, and interstitial cells. The two latter types of

FIG. 28. — Various stages in the development of the Graafian follicle of the
rabbit. (From Schafer.)

A, From young rabbit, showing Pfltiger's egg-tubes ; B, C, D, E, successive

later stages.

cell may remain for a time as reserve cells or may be absorbed as
pabulum for the developing cocyte.

The changes involved in the production of ova have been fully
investigated by von Winiwarter l in the rabbit. These changes

1 Von Winiwarter, "Eecherches sur 1'Ovogenese de 1'Organogenese de
1'Ovaire des Mammiferes," Arch, de Biol., vol. xvii., 1900.

n6 THE PHYSIOLOGY OF REPRODUCTION

which chiefly concern the chromatin of the nucleus may be
summarised as follows : —

I. Early changes : («) Protobroque cells, Variety a. — The nuclei
are granular in appearance, the chromatin is arranged irregularly,
and there is no reticulum. These are the original germinal epithelial
nuclei. (b) Protobroque cells, Variety b. — The cells belonging to

Early ovogenetic stage.

Leptotenic stage.

FIG. 29. — Developing ova from ovary two days before birth. (After
Lane-Claypon.)

variety a divide, and give rise to more cells of the same kind, as
well as to protobroque cells of the b variety. In the latter the
nuclei are less granular, and contain a certain number of fine
chromatin filaments, (c) Deutobroque cells. — The protobroque cells

Early. Synaptenic stage. Late.

FIG. 30. — Developing ova from ovary about one day before birth.
(After Lane-Claypon.)

of the b variety likewise divide, and give rise to more protobroque
cells, similar to themselves and also to deutobroque cells. These
latter are larger in size, and contain nuclei with the chromatin
arranged in the form of a reticulum.

II. Later changes: (a) Leptotenic stage. — Certain of the
deutobroque nuclei become gradually differentiated, the chromatin
during the leptotenic stage passing through a process in which it
breaks up into fine filaments ; these are distributed over the nuclear
region, (b) Synaptenic stage. — The filaments become congregated

CHANGES IN THE OVARY

117

together in the form of a lump, or dark mass, heaped up at one side
of the nuclear region, (c) Pachytenic stage. — The nuclear filaments
again become unwound, and spread themselves out over the whole
nuclear region; they are, however, considerably coarser than in the
earlier stages, (d) Diplotenic stage. — The chroinatin strands split

Pachytenic stage.
FIG. 31. — Developing ova from ovary one day after birth. (After Lane-Clay pon.)

along their whole length, and the two halves of each strand at first
lie in pairs near to one another, (e) Dictyate stage. — The split
strands pass away from one another, and the chromatin generally

Diplotenic nucleus three days
after birth.

Dictyate nucleus seven days
after birth.

FIG. 32. — Developing ova. (After Lane-Claypon.)

becomes distributed once more throughout the nuclear region in the
form of a reticulum.

The nucleus or germinal vesicle of the primordial ovum thus
produced then enters upon a long period of rest, the changes
involved in oogenesis having been completed.1

1 For an account of the minute structure of the Mammalian egg, together
with a resume of the literature, see van der Stricht, " La Structure de 1'CEuf
des Mammiferes," Part I., Arch, de Biol., vol. xxi., 1904 ; Part II., Bull, de
VAcad. Royale de Me'decine de Belgique, Bruxelles, 1905 ; Part III., Bruxelles,

ii8 THE PHYSIOLOGY OF REPRODUCTION

Some of the deutobroque cells, instead of passing through the
transformations above described, rest for a time and subsequently
undergo retrogressive changes, becoming converted, according to
Miss Lane-Claypon, either into follicular epithelial cells or into
interstitial cells. " Every cell of the germinal epithelium is probably
a potential ovum, relatively very few remaining in the protobroque
state, although some may still be seen at the periphery in ovaries of
the eighteenth day [of gestation in the rabbit]. Incomparably the

felS*t£^ if. S^$&®$$

>** 4Pr7 v*""'*

m^^M^m^

toJ5- A . liV 4£- '&%?

FIG. 33. — Ovary at birth, showing primordial follicles, x 300.
(From Williams' Obstetrics, Appleton & Co.)

greater part pass into the deutobroque state, preparatory, doubtless,
to the formation of ova. All cannot become ova, for the other forms
of cell are necessary for the maintenance of the ovarian functions ;
possibly, therefore, only the most robust cells, and those which are
most conveniently situated for obtaining nourishment, undergo the
ovogenetic changes. This suggestion would seem to be borne out by
the fact that many more of the central cells, which are nearer the

1909. For a general account of the egg and the phenomena of oogenesis in
the different groups of animals, both Vertebrate and Invertebrate, with a
complete bibliography, see Waldeyer, " Die Geschlechtszellen," in Hertwig's
Handbuch der Entwicklungslehre der Wirbeltiere, vol. i., Jena, 1903 ; also Wilson,
The Cell in Development and Inheritance, 2nd Edition, New York, 1900.

CHANGES IN THE OVARY 119

food supply, undergo ovogenesis than of the peripheral ones. The
rest of the cells, which are not able, for one cause or another, to
undergo these changes, appear to remain quiescent for a while, until
finally they regress, and pass into a condition of subserviency to the
needs of those which have become ova. Both follicle-cells and
interstitial cells are, however, still potential ova. They have passed
through the initial stages, and only need enlargement and nuclear
transformations in order to become ova should the appropriate
stimulus be given [as will be described below, p. 155]. This chance
is not given to the follicle-cells. As soon as the follicles begin to
grow they multiply rapidly, and probably provide, by their [partial]
disintegration, the follicular secretion upon which the ovum feeds
and grows." 1

The description given above of the origin of the follicle and
interstitial cells applies especially to the rabbit. Miss Lane-Claypon
has also investigated their developmental history in the rat,2 and
expresses belief that in this animal also they are derived from the
germinal epithelium by a similar process of differentiation. Both
follicular epithelial cells and interstitial cells are stated to pass
through identically the same stages, but the latter are said to remain
grouped together in the spaces between the follicles instead of
arranging themselves around the diplotenic nuclei of the develop-
ing ova.

Thus it appears that the ova, the follicular epithelial cells, and
most probably also the interstitial cells, are all derived from the
germinal epithelium by processes involving changes in the nuclear
chromatin ; but that, whereas these changes are similar in the case
of the follicle and interstitial cells, those undergone by the developing
ova are more extensive and show a greater complexity.

The significance of the common origin of these different ovarian
elements will be more apparent when we consider the views which
are held regarding the further development and the probable functional
importance of these cells.

It should be mentioned, however, that Allen3 and Sainmont,4
working on the organogenesis of the ovary in the rabbit and the cat
respectively, have come to the conclusion that the ovarian interstitial

1 Lane-Claypon, loc. cit.

- Lane-Claypon, " On Ovogeneais and the Formation of the Interstitial
Cells of the Ovary," Jour. Obstet. and Gyncec., vol. xi., 1907.

3 Allen, "The Embryonic Development of the Ovary and Testis of the
Mammals," Amer. Jour, of Anat., vol. iii., 1904. Allen describes the inter-
stitial cells in a three -months-old rabbit as being derived from certain cells in

. the thecse internee of degenerate follicles. The cells are said to lose their
walls, become irregular in shape, and undergo a rapid process of amitotic
division, after which they become transformed into typical interstitial cells.

4 Sainmont, " Recherches relatives a 1'organogenese du Testicule et 1'Ovaire
chez le Chat," Arch, de Biol., vol. xxii., 1905.

120 THE PHYSIOLOGY OF REPRODUCTION

cells have a connective tissue origin, but these investigators do not
appear to have traced the successive stages of cellular development
with the same completeness as Miss Lane-Claypon.1 Sainmont is of
opinion that they have a trophic function, a suggestion which was
first made by Pfliiger.2

There would seem to be no doubt that the developing ova in the
immature ovary subsist and grow at the expense of the surrounding
tissue. Thus protoplasmic masses, formed by the aggregation of
very young ova, have been described by Balfour,3 who made the
suggestion that one ovum may develop at the cost of the others.
These aggregations of ova were noticed in the ovary of the foatal
rabbit at about the sixteenth day of pregnancy. A day or two
previously the ova were observed to be separate. Miss Lane-Claypon,
who confirms the observation, is of opinion that Balfour's suggestion
was right, and that the ova which disappear serve ultimately as
food-stuff for the one ovum whose condition happens to be the most
vigorous. " This cannibalism on the part of the young ovum is not
surprising, if the life of an ovum be considered. It is really but the
normal condition of the cell at all its stages of development ; it grows
and fattens at the expense of other cells. In the young ovary, it is
starting its first stage of growth and must devour other cells ; later
on, during the growth of the follicle, it lives upon the follicle-cells,
and later still, when, after fertilisation, the [term] ovuni in its
extended sense refers to the young foetus, [this latter] lives on the
material provided by the cells of the maternal organism." 4

MATURATION AND OVULATION

The youngest and smallest Graafian follicles lie near the surface
of the ovary, but pass inwards as they increase in size. The large,
mature follicles, however, come to lie just below the surface from
which they begin to protrude visibly at the approach of the breeding
season. During the prooestrum one or more follicles (the number
varying in different animals, according to the size of the litter) may

1 According to Popoff (Arch, de Biol., vol. xxvi., 1911) the origin of the
interstitial cells may vary with the species (mole, stoat, dog). For description
of interstitial cells in the guinea-pig see Atkins (Anat. Anz., vol. xxxix., 1911),
and in man see Wolz (Arch. f. GyndL, vol. xcvii., 1912), and see above, p. 114.
See also Schaeffer (Arch. f. Gynak., vol. xciv., 1911).

2 Pfliiger, Ueber die Eierstocke der Saugethiere und des Menschen, Leipzig,
1863.

3 Balfour, loc. cit.

4 Lane-Claypon, "On Ovogenesis, etc.," loc. cit. That one ovum may de-
velop at the expense of others is particularly well shown in Hydra, Tiibularia,
and certain other Coslenterates. The nuclei of the ingested ova continue to
be easily recognisable even during the early segmentation stages of the
developing egg.

CHANGES IN THE OVARY 121

generally be seen showing a very considerable protrusion, while in
some animals, such as the sow, the appearance of the ovary at this
time is not dissimilar to a bunch of grapes.

A large Graafian follicle in a mature ovary contains the following
parts: Forming the outermost part of the wall and in continuity
with the ovarian stroma is the theca externa, which is a layer of
somewhat fibrous connective tissue. Within this is the theca interna,
which is less fibrous. The two thecye are only slightly modified
ovarian stroma. Within the theca interna is the epithelial wall,
which, in the very young follicles, consists of a single layer of cells
immediately surrounding the ovum. These, as already mentioned,
multiply rapidly (by mitotic division) and give rise to a layer many
cells deep, which, as the follicle increases in size, becomes divided
into two layers, the membrana granulosa lining the follicle, and the

FIG. 34. — Young oocyte or egg surrounded by a single layer of follictilar
epithelial cells. (From van der Stricht.)

discus proligerus surrounding the ovum. The innermost cells of
the discus rest upon a thick, transparent, radially striated membrane
with a granular outer border. This is a zona radiata or xona pellucida.
The striated appearance is due to the presence of fine canals. Within
the xona, and immediately enclosing the ovum, another very thin
membrane can sometimes be made out. This is the vitelline mem-
brane. The membrana granulosa and discus proligerus are united
by one or more strands of follicular epithelial cells. A viscid fluid,
containing protein matter, collects between them and becomes gradu-
ally increased in quantity as the follicle continues to grow.1

1 Occasionally a Graafian follicle may contain more than one ovum, but
this is abnormal. Such follicles have been described as occurring in the
rabbit's ovary by Honore (" Recherches sur 1'Ovarie du Lapin," Arch, ife
Siol., vol. xvii., 1901), and in the dog's ovary by Smyth ("An Unusual Graafian
Follicle," Biol. Bull., vol. xiv., 1908). The latter writer states that one follicle
contained seven ova. He shows that the tendency to produce multiple ova
may be hereditary, and that it is apparently correlated with a high fertility.
Multiovular follicles have also been observed in pigs by Corner (The Cm-pus
Liiteum, etc., Carnegie Institute (Washington) Publication 222, 1915), and in

122 THE PHYSIOLOGY OF REPRODUCTION

According to Walsh l the growth energy of the granulosa cells in
the guinea-pig is slow in small follicles ; then a gradual rise takes
place until the follicle attains medium size ; later there is a gradual
fall in growth energy until in large follicles the proliferative power
sinks almost to zero as maturity is reached.

The liquor folliculi begins to form in the developing rat's ovary
at about the ninth day of pregnancy.2 Miss Lane-Claypon suggests
that the karyolytic changes which occur in the nuclei of the follicular
epithelial cells may have some connection with the origin of the

FIG. 35. — Young human Graafian follicle. The cavity contains
the liquor folliculi. (From Sellheim.)

liquor. She states, however, that in the process of formation of the
liquor folliculi in the adult ovary, the follicle-cells appear simply to
disintegrateand dissolve without showing the phenomenaof karyolysis.
On the other hand Honore,3 who has investigated the subject in the

Dasyurm by O'Donoghue (" The Corpus Luteum, etc., and Polyovular Follicles
in Dasyurm" Anat. Am., vol. xli., 1912). Leo Loeb has discussed the formation
of plurioval follicles which he says may originate either by connective tissue
failing to grow between the eggs in an early stage, or by very small follicles
pushing their way into larger follicles. Both methods depend upon the
inactivity of the connective tissue, which is probably due to underfeeding, as
Loeb has shown ("The Concrescence of Follicles in the Hypotypical Ovary ,2.'
Biol. Bull., vol. xxxiii., 1917).

1 Walsh, "The Growth of the Ovarian Follicle of the Guinea-Pig under
Normal and Pathological Conditions," Jour. Exp. Med., vol. xxvi., 1917.

2 Lane-Claypon, loc. cit.

3 Honore, "Recherches sur 1'Ovarie du Lapin," Arch, de Biol., vol. xvi.,
1900.

CHANGES IN THE OVARY

123

case of the rabbit, concludes that the liquor folliculi is secreted by the
follicle-cells, without their undergoing destruction (or that.if this occur,
it is immaterial to the process of liquor formation), in the same way
as the urine is secreted by the epithelium of the renal tubules. In
support of this view Honore points out that there are no indications
of degeneration or destruction of the follicular epithelial cells of the
ripe follicles during oestrus, and moreover, that these cells are retained
in the follicle at the time of ovulation, giving rise subsequently to

FIG. 36. — Human ovum at termination of growth period. (After van der
Stricht.) Yolk granules, vacuoles, and fat drops are seen.

the luteal cells of the corpus luteum. It would appear possible,
however, that the liquor folliculi is formed partly by the secretory
activity, and partly by destruction of the follicle-cells, just as,
according to one view, milk is derived from both the secretion and
the disintegration of the cells of the mammary gland (see p. 592).1

Heape2 states that during the growth of the ovum nourishment
is supplied to it by the aid of the discus proligerus, for fine proto-

1 For rate of growth in avian ova, see Eiddle (" Studies on the Physiology
of Reproduction in Birds," Amer. Jour, of Physiol., vol. xli., 1916). Riddle states
that yolk formation is not necessarily connected with the production of ova
(Bid. Bull., vol. xxii., 1912).

2 Heape, "The Development of the Mole," Quar. Jour. Micr. Science,
vol. xxvi., 1886.

i24 THE PHYSIOLOGY OF REPRODUCTION

plasmic processes may be seen passing from the cells of this layer
and projecting into radiating canals in the zona which encloses the
ovum, being in contact with the vitelline membrane.

Immediately after copulation, and therefore during cpstrus, the

FIG. 37. — Human ovum examined fresh in the liquor folliculi. (From Waldeyer.)
The ovum shows yolk granules in the centre surrounding the nucleus (with
its nucleolus) and a clearer peripheral portion. It is enclosed by follicular
epithelial cells.

cells of the discus proligerus (in the rabbit)1 begin to withdraw
radially, and eventually remain attached to the zona radiata by the
extremely thin strands just referred to. At the same time the
ovum itself withdraws somewhat from the zona, leaving a narrow
circular space. These processes occupy some hours. About nine

1 In the rabbit these processes depend on coition. (Heape, " Ovulation and
Degeneration of Ova in the Kabbit," Proc. Roy. Soc., B., vol. Ixxvi., 1905.)

CHANGES IN THE OVARY 125

hours after copulation, when the supply of nourishment has been
entirely cut off, the two polar bodies are formed, and the ovum
becomes mature.1

The essential facts about the maturation process were first
ascertained by van Beneden z in Ascaris, and were afterwards studied
more fully by Boveri.3 Subsequently Montgomery4 has elucidated
the process still further by showing that prior to the formation of
the first polar body the chromatin filaments or chromosomes of the
cell nucleus conjugate together in pairs, and that in all probability
one member of each pair is a descendant of a chromosome derived
from the father, while the other member is descended from a corres-
ponding maternal chromosome.5 The possible significance of this
conjugation of chromosomes is referred to on a later page (see
p. 201). In the subsequent maturation division the chromosomes
again separate.6

The changes involved in the formation of the first polar body are
in most respects similar to those of ordinary cell division. The
centrosome, which lies in the cytoplasm, divides, and the two
daughter centrosomes thus produced travel to opposite sides of the
nucleus. In the meantime, the latter forms a spindle, the nuclear
membrane having disappeared. Each centrosome becomes surrounded
by a system of rays, and in this way the attraction spheres are
formed. The chromosomes next arrange themselves equatorially
between the attraction spheres, each one having now split into two
parts. Half of. these migrate towards each centrosome, and the nucleus
becomes divided. One of the daughter nuclei, together with a thin
investment of protoplasm, is extruded from the ovum. This is the
first polar body, which is therefore a product of unequal cell
division. Subsequently to extrusion it sometimes divides into two.
After the formation of the first polar body, the ovum again divides
in the same unequal fashion, and the second polar body is formed

1 Cf. Thomson (A.), " The Maturation of the Human Ovum," and " The Eipe
Human Graafian Follicle," Jour, of Anat., vols. liii. and liv., 1919 and 1920.

2 Van Beneden, "Recherdfies sur la Maturation de 1'CEuf," Arch, de Biol.,
vol. iv., 1883.

3 Boveri, " Zellenstudien," Jenaische Zeitsch., vol. xxi., 1887.

4 Montgomery, " Some Observations and Considerations upon the Matura-
tion Phenomena of the Germ-Cells," Biol. Bull., vol. vi., 1904.

5 The observations of this author, together with those of Sutton, McClung,
Wilson, etc., point to the conclusion that all the nuclei in the somatic cells
contain two parallel series of chromosomes (paternal and maternal).

6 In the reduction process each pair of fused chromosomes becomes divided
into a group of four bodies united by linin threads. These are the tetrads
or " vierergruppen." It follows that the number of tetrads in any particular
species is always one-half the number of somatic chromosomes. Thus, if the
somatic cells contain sixteen chromosomes, the number of tetrads formed is
eight, while, as shown in the text, the number of chromosomes in the mature
germ-cells (after reduction) is also eight.

126 THE PHYSIOLOGY OF REPRODUCTION

and extruded. The polar bodies undergo degeneration. Meanwhile
the nucleus of the ovum once more becomes surrounded by a
membrane and enters upon a resting stage.

The process of formation of the first polar body differs from that
of the second in that the chromosomes do not undergo splitting.
Consequently the nucleus of the mature ovum contains only half
the original number of chromosomes. This number varies in the
different species, but is constant in each.1 According to Duesberg
it is twenty-four in man, so that in the mature human ovum there
should be only twelve chromosomes.2

The evidence of other investigators is conflicting, von Winiwarter 3
stating that in the human female there are forty-eight chromosomes
and in the male .forty-seven. According to Guyer 4 and Montgomery 5
there are in the negro probably only half the number of chromo-
somes that there are in the white race.

As will be shown in the next chapter, the spermatozoa, or
male germ-cells, undergo a similar process of maturation, the
conjugating cells containing only half the number of chromosomes
characteristic of the species, just as in the case of the conjugating
ova.6 It has been supposed, therefore, that the reduction in the
number of chromosomes is a preparation on the part of the germ-
cells for their subsequent union, and a means by which the number
of chromosomes is held constant in each species.

The discovery that the nuclei of the conjugating cells contain
only half the number of chromosomes possessed by the soma or
body-cells was made originally by van Beneden. It has since been
extended to so many animals and plants that it may probably be
regarded as a general law of development.7.

1 Von Winiwarter, however, states that in the rabbit the number varies
from thirty-six to eighty, but is generally about forty-two (Arch, de Biol.,
vol. xvi., 1900).

2 Duesberg, " Sur le Nombre de chromosomes chez 1'Homme," Anat. Anz.,
vol. xxviii., 1906.

3 Von Winiwarter, "Etude sur la Spermatogenese humaine," Arch, de Biol.,
vol. xxvii., 1912.

4 Guyer, " Accessory Chromosomes in Man)" Biol. Bull., vol. xix., 1910 ;
Science, vol. xxxix., 1914.

6 Montgomery, "Human Spermatogenesis," Jour. Acad. Nat. Science,
Philadelphia, vol. xv., 1912.

6 But see below, footnote, p. 166.

7 For details of the process in various forms of life see Wilson, The Cell,
2nd Edition, New York, 1900. See also Doncaster, "On the Maturation of
the Unfertilised Egg, etc., in the Tenthredinidse," Quar. Jour. Micr. Science,
vol. xlix., 1906; " Gametogenesis, etc.," Prof. Roy. Soc., B., vol. Ixxxii., 1910,
and vol. Ixxxix., 1916. Doncaster shows that in the sawflies there are two
types of maturation process, in one of which there is no reduction. It is
probable that only the reduced eggs are capable of fertilisation. In other
cases, however, the ova are able to undergo parthenogenetic reproduction
without forming polar bodies. See Hewitt, " The Cytological Aspect of
Parthenogenesis in Insects," Manchester Memoirs, vol. lx., 1906 ; Doncaster,

CHANGES IN THE OVARY 127

It is commonly believed that the chromatin material is the
substance which has the potentialities of development, and which
plays the principal part in perpetuating the hereditary structure
and qualities of the particular animal or plant, but there is no real
proof that this is effected by them exclusively (see p. 204).

The maturation phenomena may take place within the ovary
prior to the discharge of the egg, or they may be postponed until
after ovulation has occurred. In the rabbit, as has been shown
already, the polar bodies are formed while the ovum is still in the
ovary, and the same is believed to be the case in man.1

In the case of the mouse, Sobotta 2 came to the conclusion that
the first polar spindle is suppressed, and that the second polar body
might be formed during the passage of the ovum down the
Fallopian tube. Gerlach 3 describes the second polar body as being
in some instances suppressed after the entry of the spermatozoon in
fertilisation, the second polar spindle degenerating within the egg.
Kirkham,4 however, states that the maturation of the mouse's
ovum is in no way exceptional, the process involving the formation
of two polar bodies as in most other animals. The first polar body
is extruded in the ovary, while the second is given off in the
Fallopian tube immediately after fertilisation by a spermatozoon.6
Rubaschkin6 has shown that the maturation processes in the
guinea-pig are similar. In both the guinea-pig and the mouse, ova
which are retained in the ovary, and also those which are discharged
and fail to become fertilised, undergo degeneration with the second
polar spindle within them.

The maturation phenomena in the bat ( Vesperugo noctula) have
been investigated by van der Stricht, who has published a series of

"Animal Parthenogenesis," /Science Progress, vol. iii., (July) 1908 ; and Cytology,
Cambridge, 1920. These works contain further references.

1 Thomson (A.), loc. cit., 1919.

2 Sobotta, " Die Befruchtung und Furchung des Eies der Maus," Arch. f.
Mikr. Anat., vol. xlv., 1895.

3 Gerlach, Ueber die Bildung der Richtungskorper bei Mu& muswdus,
Wiesbaden, 1906.

* Kirkham, "The Maturation of the Mouse Egg," Biol. Bull., vol. xii.,
1907; and "The Maturation of the Egg of the White Mouse," Trans. Con-
necticut Acad. Arts and Sciences, vol. xiii., 1907.

5 Sobotta (" Die Bildung der Richtungskorper bei der Maus," Anat. Hefte,
vol. xxxv., 1907), in a further paper, expresses himself doubtful as to whether
two polar bodies are really discharged in all cases in the maturation process
of the mouse's ovum. His own observations lead him to conclude that two
polar bodies are discharged in not more than one-fifth of the total number
of maturations, only one polar body being formed in the great majority of
cases. Lams and Doorme ("Nouvelles Recherches sur la Maturation et la
Fecondation de 1'CEuf des Mammiferes," Arch, de Biol., vol. xxiii., 1907) state
that they found two polar bodies expelled in forty-four cases out of forty-eight,
the first being always smaller than the second.

6 Rubaschkin, " Ueber die Reif ungs- und Befruchtungsprocesse des Meer-
schweincheneies," Anat. Hefte, vol. xxix., 1905.

128 THE PHYSIOLOGY OF REPRODUCTION

papers on the subject.1 This observer states that there are always
two polar bodies formed. The first is extruded in the ovary. The
second spindle is formed at about the ovulating stage, and the second
polar body is discharged in the interior of the Fallopian tube. The
first body is formed in February or March, or sometimes later
according to the temperature.2

It would seem that in the case of the mole the two polar bodies
are discharged while the ovum is still retained within the ovary.3

In the pigeon it has been shown that the polar bodies are -given
off while the ovum is passing down the glandular portion of the
oviduct and after the entrance of the spermatozoon. The first polar
spindle, however, is formed in the ovarian egg ; but it is not definitely
known at what stage fertilisation occurs, excepting that it is previous
to the time when the egg is clasped by the oviducal funnel.

In the frog the polar bodies are extruded after ovulation has
taken place, but the egg is not set free until it has reached a certain
stage of maturation, which is preparatory to the discharge of the
first polar body. The nucleus undergoes a change, and, in place of
being large and watery, consists of a small mass of chromatic
substance lying in the protoplasm. An achromatic spindle is
developed, and the chrornatin becomes arranged in the form of
granules at the equator of the spindle. The nuclear membrane
disappears with the large watery nucleus. The ova in this condition
pass into the oviducts.4

In certain Invertebrates (Nematodes, Annelids, and Gasteropods)
it has been noticed that the occurrence of the maturation phenomena
depends upon the act of fertilisation. For example, in the Japanese
Palolo-worm, a marine Polychset Annelid, Ixuka 5 has shown that the

1 Van der Stricht, " La Ponte ovarique, etc.," Bull, de I'Acad. Roy. de Med.
cle Belgique, 1901. Une Anomalie tres interessante concernant le Developpement
cPun CEuf de Mammifere, Gand, 1904. " Les Mitoses de Maturation de 1'CEuf
de Chauve-Souris," Memoire presente au VHP Congres de I'Assoc. des Anatomistes,
Nancy, 1906.

2 Van der Stricht says (La Structure de VCEuf des Mammiferes, Bruxelles,
1909) that he has seen twenty-two ova at the stage of the second polar
spindle within the ovary and twenty-seven at the same stage outside of the
ovary, the dates varying in each case from the end of February to the end
of April. See below, p. 183, Fig. 58.

3 Heape, "The Development of the Mole," Quar. Jour. Micr. Science,
vol. xxvi., 1886. For further information as to maturation phenomena, see
von Winiwarter (loc. cit., for man) ; von Winiwarter and Sainmont (Nouvelles
recherches sur Vovogenese, Liege, 1912, for cat) ; Van der Stricht (" Vitellegenese
dans 1'Ovule de Chatte," Arch, de Biol., vol. xxvi., 1911, for cat) ; and Corner
(" Maturation of the Ovum in Swine," Anat. Record, vol. xiii., 1917, for pig);
also Athias, Sobre as Divisoes de Maturacao do Ovuto dos Mammiferos, Lisbon,
1910.

4 Morgan, The Development of the Frog's Egg, New York, 1897.

5 Izuka, " Observations on the Japanese Palolo," Jour, of the Coll. of Science,
University of Tokyo, vol. xvii., 1903.

CHANGES IN THE OVARY 129

first polar body is discharged (after certain preparatory changes) one
hour after fertilisation by a spermatozoon, and that the second polar
body is extruded fifteen or twenty minutes later. In other animals
(e.g. Amphioxus), one maturation process takes place before, the other
during the entrance of the spermatozoon.1

It would appear from these facts that the maturation processes
in many animals only take place as a result of a specific stimulus
which may be induced by the act of copulation, or may be caused
only by the entry of the spermatozoon into the protoplasm of the
ovum. It would seem, on the other hand, that in some animals
maturation takes place independently of any stimulus at such time
as the follicle has attained to a sufficient degree of ripeness or after
it has discharged its ovum.2

It has already been shown incidentally that the processes of
maturation and ovulation are intimately associated, and that the
latter, like the former, is in many animals dependent for its
occurrence upon a definite physiological stimulus. The Graafian
follicle may rupture when the egg has reached a certain degree of
maturity, or it may require the additional stimulus of sexual inter-
course before ovulation can be induced.

In the rabbit ovulation takes place about ten hours after coition.3
The ovum, which is entirely free from follicular epithelial cells, is
discharged into the infundibulum which at this time closely invests
the ovary. The discharged ovum is incapable of assimilating
nutriment unless it becomes fertilised, and if fertilisation is not
effected it undergoes degeneration. Heape found that ovulation
could not be induced by artificial insemination, nor by any means
other than sexual intercourse, and moreover, that intercourse was a
sufficient stimulus, even when the progress of the spermatozoa from
the vagina into the uterus was artificially stopped, provided that
there was no interference with the vascular supply to the
ovaries.

It is stated by Weil 4 that ovulation may take place independently

1 See Przibram, Embryogeny, English Translation, Cambridge, 1908.

2 The chemistry of the maturation process is discussed by Mathews ("A
Contribution to the Chemistry of Cell Division, Maturation and Fertilisation,"
Amer. Jour, of Phys., vol. xviii., 1907). This author describes the maturation
of the egg of Asterias as being inaugurated by the dissolution of the nuclear
membrane. If oxygen is withheld the mature egg soon dies. It is believed
that an "oxidase" escapes from the nucleus into the cytoplasm on the
rupture of the nucleus. The astral radiations disappear if oxygen is with-
drawn, but reappear if oxygen is readmitted. It is concluded that the astral
figures are the product of three substances : (1) centriole substance ; (2) oxidase ;
and (3) oxygen.

3 Heape, loc. tit. The maturation processes also depend on coition.

4 Weil, " Beitrage zur Kenntniss der Befruchtung und Entwickelung des
Kanincheneies/' Wien. Med. Jahrbuch, 1873.

130 THE PHYSIOLOGY OF REPRODUCTION

of coition in rabbits which have given birth to young just previously,
and Iwanoff,1 in confirmation of this statement, records experiments
in which pregnancy was induced in rabbits by the artificial injection
of seminal fluid shortly after parturition (cf. p. 102).

In the mouse,2 the rat,3 and the guinea-pig,4 ovulation occurs
spontaneously during " heat," and generally, if not invariably, during
O3strus.5

In the dog ovulation takes place independently of coition after
external bleeding has been going on for some days, or when it is
almost or quite over ; in other words, it occurs during oestrus and
not during the prooestrum, or at any rate not during the early stages
of the prooestrum.® It is probable that the sow also ovulates during
oestrus and not during the prooestrum, since it is stated that sows are
most successfully served on the second or third day of "heat."7
Coition, if it occurs earlier, is frequently not followed by conception.8
From Hausmann's description it would seem that ovulation does
not take place prior to coition, but this conclusion is certainly
incorrect.9

In the ferret ovulation occurs during oestrus, but postponement
of coition may bring about the degeneration of the ripe follicles,
since they do not usually discharge spontaneously.10

Robinson,11 who has made a very close study of the phenomenon of
maturation and ovulation in the ferret, states that the time intervening
between insemination and follicular rupture may vary from 3(H hours
to 93A hours.

1 Iwanotf, " La Fonction des Vesicles seminales et de la Glande prostatique,"
Jour, de Phys. et de Path. Gen., vol. ii., 1900.

2 Sobotta, loc. cit. See also Kirkham, " Ovulation in Mammals, etc.," Biol.
Evil., vol. xviii., 1910.

3 Tafani, " La Fecondation et la Segmentation studiees dans les CEufs des
Eattes," Arch. Ital. de Biol., vol. ii., 1889. Cf. Kirkham, loc. cit.

4 Rubaschkin, loc. cit. See also Loeb (L.), "The Cyclic Changes in the Ovary
of the Guinea-pig," Jour, of Alorph., vol. xxii., 1911.

5 According to Smith (H. P.) the ovarian cycle in mice varies from sixteen to
nineteen days (Proc. Amer. Assoc. A hat. (No. 55), Anat. Record, vol. xi., 1917).
According to Long and Quisno, rats ovulate every ten days (Science, vol. xliv.,
1916).

6 Marshall and Jolly, "Contributions to the Physiology of Mammalian
Reproduction : Part I. The (Estrous Cycle in the Dog," Phil. Trans., B.,
vol. cxcviii., 1905.

7 See Mackenzie and Marshall, "On Ovariotomy in Sows," Jour, of Agric.
Science, vol. iv., 1912. According to Corner and Ausbaugh, ovulation may
occur before the third day of heat, Anat. Record, vol. xii., 1917.

8 Wallace (R.), Farm Live Stock of Great Britain, 4th Edition, London, 1907.

9 Hausmann, Ueber die Zeugung und Entstehung des wahren weiblichen Eies,
etc., Hanover, 1840.

10 Marshall, " The CEstrous Cycle in the Common Ferret," Quar. Jour. Micr.
Science, vol. xlviii., 1904.

11 Robinson, "The Formation, Rupture, and Closure of Ovarian Follicles
in Ferrets, etc.," Trans. Roy. Hoc. Edin., vol. lii., 1918.

CHANGES IN THE OVARY 131

Longley has shown that in the cat ovulation takes place only
after coition.1

Artificial insemination, followed by pregnancy, has been success-
fully performed on mares, donkeys, and cows.2 Consequently it may
be concluded that these animals ovulate independently of coition.
According to Ewart,3 ovulation in the mare very often does not occur
until near the end of the oestrous period.

It has been shown also tljat the sheep ovulates spontaneously at
each of the earlier heat periods of the sexual season, but that there
are reasons for believing that during the later periods the stimulating
power at the disposal of the ewes may be so reduced that without
coition it is incapable of causing ovulation. There is also evidence
that when coition occurs at the beginning of an oestrous period, it
may provide a stimulus inducing ovulation to take place a few hours
earlier than it otherwise would; in other words, that if ovulation
has not already occurred during an oestrus, the stimulus set up by
coition may hasten the rupture of the follicle.4 Eecently Iwanoff
has succeeded in inducing pregnancy in sheep by artificial insemination.
(See p. 176).

There can be little doubt that in the great majority of Mammals
ovulation, as a general rule, occurs regularly during oestrus. In
certain bats, however, copulation is performed during the autumn,
whereas ovulation is postponed until the following spring, the animals
in -the meantime hibernating, while the spermatozoa are stored up in
the uterus (see p. 170).5 The ovary in the winter months (during
the hibernating period) is said to be in a state of quiescence, and the
exact time for maturation and ovulation depend upon the temperature
of the early months of the year, occurring generally in February or
March, but sometimes as late as April.6 Ovulation takes place some

1 Longley, " Maturation of the Egg and Ovulation in the Domestic Cat,'
Amer. Jour, of Anat., vol. xii., 1911. Doncaster has recorded that a female cat,
after copulating with a sterile tortoiseshell male, secreted milk about four weeks
later, and continued to do so for two weeks, but without experiencing pregnancy.
This was clearly a case of pseudo-pregnancy comparable to what occurs in
Dasyurus, the dog, and the rabbit under experimental conditions. See p. 36.
("A Possible Connection between Abnormal Sex-limited Transmission and
Sterility," Camb. Phil. Soc. Proc., vol. xvii., 1913.)

2 Heape, "The Artificial Insemination of Mammals," Proc. Roy. Soc., vol.
Ixi., 1897. There is direct evidence of spontaneous ovulation in cows.

3 Ewart, " Studies on the Development of the Horse," Trans. Roy. Soc. Edin.,
vol. li., 1915.

4 Marshall, " The (Estrous Cycle and the Formation of the Corpus Luteum
in the Sheep," Phil. Trans., B., vol. cxcvi., 1903.

5 Benecke, "Ueber Reifung und Befruchtung des Eies bei den Fleder-
mausen," Zool. Anz., vol. ii., 1879. Eimer, " Ueber die Fortpflanzung der
Fledermause," Zool. Am., vol. ii., 1879. Van Beneden and Julin, "Observa-
tions sur la Maturation, la Fecondation, et la Segmentation de 1'CEuf chez les
Cheiropteres," Arch, de Biol., vol. i., 1880.

6 Van der Stricht, "L'Atresie ovulaire, etc.," Verkand. d. Anat. Gesell. in
Bonn, 1901. LVS Mitoses de Maturation, etc., Nancy, 1906.

132 THE PHYSIOLOGY OF REPRODUCTION

days or even weeks after the formation of the first polar body.
It would appear, then, that in bats the follicles can discharge
spontaneously under the influence of appropriate seasonable stimuli,
and without even the occurrence of oestrus.1

There has been a considerable amount of controversy regarding
the periods at which ovulation occurs in the Primates, the question
being discussed at some length in three papers by Heape.2 This
author has shown that ovulation and menstruation are not associated
in monkeys (at any rate not necessarily), and that whereas, in
both monkeys and the human species, menstruation may occur
periodically all the year round, in monkeys there is a limited season
for conception and ovulation ; while in civilised woman this period
is not limited to any particular time of the year, although there is
evidence that primitive man agreed with the lower Primates in
having a definite sexual season (during which ovulation occurred).
(See p. 64.) Van Herwerderi 3 has adduced further evidence which
shows that there is no apparent connection between ovulation and
menstruation, either in monkeys or in the aberrant lemur, Tarsius
spectrum. It would seem probable, however, in view of Pocock's
observations4 upon the occurrence of a pronounced post-menstrual
oestrus in certain monkeys in the Zoological Gardens, that ovulation
may take place at this period (that is, at the close of menstruation).

In the case of the human female there is still a great divergence
of opinion in regard to the usual time for the discharge of the ova.
Some authors express the belief that ovulation occurs before
menstruation, others that it takes place during that process, and
others again that it follows menstruation. Hergesell5 has lately
adduced evidence which, in his opinion, points to the conclusion that
ovulation precedes menstruation, but the occurrence of corpora lutea
of uncertain age in the ovary cannot be regarded as supplying
definite proof. .There are reasons, on the other hand, for concluding
that, primitively at any rate, the most usual period for ovulation in
the human female was during a definite oestrus following a pro-
cestrum, as in many of the lower Mammals ; for the period of most
acute sexual feeling is generally just after the close of the menstrual

1 In some Invertebrata which undergo cyclical changes it has been shown
that ovulation occurs only at certain intervals depending upon the general
condition of the organism. Thus in the females of certain Crustacea ovulation
regularly follows the moult and cannot precede it. — Science (New Series),
vol. xxv. (Feb. 1907).

2 Heape, Phil. Trans., B., vol. clxxxv., 1894, and vol. clxxxviii., 1897.
Trans. Obstet. Soc., vol. xl., 1898.

3 Van Herwerden, " Bijdrage tot de Kennis van den Menstruellen Cyclus,"
Tijdschr. d. Ned. Dierk. Vereen, vol. x., 1906.

4 Pocock, "Notes upon Menstruation, etc.," Proc. Zool. Soc., 1906.

6 Hergesell, " Das zeitliche Verhalten der Ovulation zur Menstruation,"
Inang. Diss., Leipzig, 1905. Cf. Nielsen, p. 107.

CHANGES IN THE OVARY 133

period (see p. 64), while, according to Raciborsky, this is also the
commonest season for fertile coition.1 Moreover, the facts narrated
by Bryce and Teacher, in a recent memoir on the early development
and embedding of the human ovum, render it extremely probable
that the ovum described had been discharged shortly after the
cessation of the last menstruation.2

With regard to the question as to whether any special stimulus
is necessary to induce ovulation in women, Oliver 3 is of opinion that
whereas it sometimes may occur spontaneously, it is more than
probable that it " may be and often is accelerated by coitus," since
at this time there is "an increased determination of blood to the
whole genital tract."4

This suggestion receives some support from an experiment by
Clark,5 who caused the rupture of a Graafian follicle artificially in a
freshly removed ovary by injecting carmine gelatine into the vessels
and so raising the ovarian blood pressure.

The causes which determine the rupture of the Graafian follicle
are also discussed by Heape,0 who is of opinion that this is brought
about in the rabbit by the stimulation of erectile tissue, and not
simply as the result of internal pressure arising from increased

1 Raciborsky, Traite de Menstruation, Paris. See also Luciani, Human
Physiology, English Edit., vol. v., London, 1921. Oliver thinks that fertilisation
may take place at practically any time in the inter-menstrual period ("Fertilisa-
tion Time and the Inception of Gestation in Women," Edin. Med. Jour., 1914.
See also Fraenkel, " Ovulation, Konzeption und Schwangerschaf tsdauer,"
Zeitsch. five Oeb. und Gyn., vol. Ixxiv. ; and Tschirdewahn, " Ueber Ovulation,
Corpus Luteum und Menstruation," Zeitsch. fur Geb. und Gyn., vol. Ixxxiii.

* Bryce and Teacher, Contribution to the Study of the Early Development and
Embedding of the Human Ovum, Glasgow, 1908.

3 Oliver, " A Study of Fertilisation with Beference to the Occurrence of
Ectopic Pregnancy," Edin. Med. Jour., vol. liv., 1902.

4 Pregnancy, and therefore ovulation, have been known to take place before
the onset of menstruation. Pregnancy may also occur during amenorrhoea (e.g.
at the commencement of the menopause) and during the lactation period, when
menstruation is often in abeyance. Again, it is stated that ovulation has been
noted during infancy, before any of the other indications of puberty have been
observed (Webster, " The Biological Basis of Menstruation," Montreal Medical
Journal, April 1897). Further, it will be shown below (p. 378) that the ovaries
can maintain their normal functions after the removal of the uterus. It would
seem, therefore, that ovulation mat/ occur spontaneously in women, and is not
necessarily connected with either menstruation, oestrus, or coitus. On the other
hand, there is evidence that ovulation is usually dependent upon the occur-
rence of the sexual orgasm in women. Galabin records a case of a woman who
married under the age of twenty, and lived in married life with two husbanda
in succession, and who, when she had passed the age of forty, experienced the
sexual orgasm in coitus for the first time, and from that day dated her first and
only pregnancy (Manual of Midwifery, 6th Edition, London, 1904). That the
orgasm (which is characterised by the erection of the clitoris, etc., accompanied
by pleasurable sensations) is not absolutely necessary for conception is shown
further by pregnancy occasionally occurring in women who are " impotent."

5 Clark, " The Origin, Development, and Degeneration of the Blood- Vessels
of the Human Ovary," Johns Hopkins Hospital Reports, vol. ix,, 1900.

6 Heape, " Ovulation, etc.," Proc. Roy. Soc., B., vol. Ixxvi., 1905.

134 THE PHYSIOLOGY OF REPRODUCTION

vascularity or a greater quantity of liquor folliculi.1 In this animal
the process must be due to a nervous reflex, induced by the act of
copulation. Robinson2 states that in the ferret ovulation is due
to the formation of a secondary liquor folliculi which makes its
appearance in the epithelial cells surrounding the ovum and which
follows successful insemination. The process is unaccompanied by
bleeding. According to Stockard 3 ovulation is caused by congestion
of the theca interim, but as has been shown above, in those animals
in which the ova are discharged spontaneously, this usually occurs
during oestrus, and not during the prooestrum when the congestion
of the generative tract is at its height. Moreover, as described
below, congestion and haemorrhage into the cavity of the follicle
in the rabbit may occur without rupture, the ovum and epithelial
cells being retained and eventually undergoing atrophy. Further-
more, Schochet4 has expressed the view that ovulation is not
mechanical or due to pressure, but occurs as a result of digestive
action on the part of the liquor folliculi.

Harper's experiments5 on the fertilisation of the pigeon's egg
elucidate the question somewhat further. This author writes as
follows : " When a pair [of pigeons] ready for mating is put together,
egg-laying ordinarily ensues at the end of a rather definite period,
at the least eight days. The female functions are held in abeyance
till the proper stimulus is received from a mate.6 The maturing of
the egg is so exclusively a female function that it seems odd at first
thought that an apparent exception should occur to the rule. Of
course, we know that the final maturation of the egg, or the giving
off of the polar bodies, awaits in most animals the act of fertilisation.
But here the effect is produced upon the egg by the entrance of
sperms. How mating and the act of copulation [which is repeated
at frequent intervals every day at this time] could' influence the
ripening of the egg in the ovary is another problem. , In this
connection the curious fact must be mentioned that two female
pigeons placed in confinement may both take to laying eggs.7 The

1 It has been suggested that the follicle may rupture as a result of the
breaking down of the blood-vessels in its wall, and the consequently increased
pressure due to the bleeding into the cavity. See Heape.

2 Robinson, loc. tit.

3 Stockard and Papanicolaou, "The Existence of a Typical (Estrous Cycle in
the Guinea-pig," Ainer. Jour, of Anat.t vol. xxii., 1917.

4 Schochet, " A Suggestion as to the Process of Ovulation and Ovarian Cyst
Formation," Anat. Record, vol. x., 1916.

5 Harper, " The Fertilisation and Early Development of the Pigeon's Egg,"
Amer. Jour, of Anat., vol. iii., 1904.

6 In the common fowl, and probably in most other birds, ovulation takes
place independently of the male.

7 I am informed by an experienced breeder of pigeons that if overfed an
isolated female may lay a few eggs in the course of a year.

CHANGES IN THE OVARY 135

function of ovulation is in a state of tension, so to speak, that
requires only a slight stimulus, 'mental' apparently in this case,
to set the mechanism to working. At any rate, it is impossible to
regard the presence of sperm in the oviduct as an essential element
of the stimulus to ovulation, although it may have an important
influence in the normal case. Our attention is directed to the
various and complex instincts of the male which come under the
head of courtship, both before and after mating is effected, as
furnishing a part of the stimulus to the female reproductive organs."
Harper proceeds to describe a curious habit which is common among
pigeons before copulating. The male bird regurgitates some secre-
tion in its throat, and this is taken up by the bill of the female in
much the same manner as the young take their food. " It is easy
to see that here may be one of the sources of indirect stimulation
to the female reproductive organs."

Spallanzani l found that whereas the female fire-bellied toad could
lay its eggs in the absence of the male, the. female fetid toad, if
isolated, retained its eggs in the ovaries. The common frog is
capable of spontaneous .oviposition, at least in some cases.2

The exact nature of the mechanism by means of which the
discharged ova in the human female are made to pass into the
aperture of the oviduct is not certainly known. Rouget 3 believed
that the firnbriated end of the Fallopian tube erected and partially
enclosed the ovary. Kehrer4 suggested that the ovum was shot
into the open fimbriai in the act of ejaculation. The motion of the
cilia, which line the fimbriated end as well as the interior of the
tube, no doubt serve to set up a current which assists in directing
the ova. The finibria-, therefore, act as an aspirator. Gerhardt,5 who
has paid some attention to the question, concludes that in man and
many other Primates a number of factors co-operate to secure the
entry of the discharged ovum into the tube. These factors include
the erectibility of the fimbrite, the muscular movements of the same,
the ciliary currents on the fimbriaj and tube, and the configuration
of the ovarian surface. In other orders of Mammals the process is
brought about in various ways. In Monotrernes, Marsupials, and
Cetaceans the entrance to the tube is relatively large as compared
with the size of the ovary. In certain other animals a portion of

1 Spallanzani, Dissertations, English Translation, London, 1784.

2 Morgan, The Development of the frog's Egg, New York, 1897.

3 Rouget, " Reehertihes sur les Organes Erectiles de la Fennne," Jour, de
la Phys., vol. i., ISSSr1"1}

4 Kehrer, " Dife ZusamnietaKiehungen des Weiblichen Genitalcanals," Beitrcige
zur Vergleibh. und Exper. (iebitrtdkuhde, 1864.

5 Gerhardt, "Studien iiber den Geschlechtsapparat der Weiblichen Sauge-
thiere : I. Die Ueberleitung deff Eies in die Tuben," Jenaischc Zeitsch.,
vol. xxxix., 1905.

136 THE PHYSIOLOGY OF REPRODUCTION

the peritoneum is used as a common envelope for the ovary and the
end of the tube. Thus in the dog and ferret the ovary is enclosed
in a sac communicating with the cavity of the tube, so that the
discharged ova can scarcely fail to effect an entrance into the uterus.
There can be little doubt, however, that in the majority of animals
ciliary movement plays an important part in directing the course of
the expelled ova.

Nussbaum * has described the eggs of the frog as being carried
into the mouths of the oviducts by the motion of the cilia of the
crclomic epithelium. These cilia are said to drive in a forward
direction any small bodies lying free in the coalom. Harper2 states
that in the pigeon the egg is clasped by the oviduct, which at this
time displays active peristaltic contractions, as if in the act of
swallowing the egg.

There is evidence, however, that ova which are discharged from
one ovary do not always pass into the oviduct on .the corresponding
side. For example, instances have been known of animals with a
bicornuate uterus becoming pregnant in the uterine horn on the
side opposite to that on wrhich the ovary had discharged (as indicated
by the presence of a newly formed corpus luteum). Moreover, it
has been recorded that animals from which one ovary had been
removed have become pregnant in the uterine horn of the other
side, an observation which indicates that the ova which are discharged
from one ovary may travel across the peritoneal cavity and enter
the Fallopian tube which was connected with the other ovary.3

It has been stated that in certain abnormal cases an ovum which
escapes altogether into the peritoneal cavity may yet become fertilised,
bringing about a condition of abdominal pregnancy. There can be
little doubt, however, that abdominal pregnancy is nearly always
secondary to tubal pregnancy, and that primary ectopic pregnancy
is exceedingly rare. According to Loeb 4 the uterine mucosa is the
only form of tissue which is able to produce a decidua in the guinea-
pig, and while an ovum in the body cavity may undergo the early
stages of development, lack of the proper response on the part of the
host-tissue (lack of decidual reaction) renders development of the
later stages of extra-uterine growth impossible Blair Bell,5 however,

1 Nussbaum, "Zur Mechanik der Eiablage bei Rana fusca" Arch. f. Mikr.
Anat., vol. xlvi., 1895. 2 Harper, loc. cit.

3 Cf. Hammond, "On some Factors Controlling Fertility in Domestic
Animals," Jour. Agric. Science, vol. vi., 1914 (for rabbits and pigs), and Corner,
"The Corpus Luteum of Pregnancy as it is in Swine," Contribution* to
Embryology, vol. ii., Carnegie Institute Pub., 1915. Internal migration of ova
from one uterine horn to another has been shown to be not uncommon.

* Loeb (L.), " The Experimental Production of an Early Stage of Extrauterine
Pregnancy," Pnx-. Av<e. Exp. ttiol. 3/ed., vol. xi., 1914.

5 Blair Bell, '" Primary Abdominal Pregnancy in a Rabbit," Proc. Roy. Soc.
Ned., 1911.

CHANGES IN THE OVARY 137

has described a case of primary abdominal pregnancy in the rabbit
where four foetuses were found attached to the gastro-colic omentum.
Gofton * has described a case of a cat which was pregnant with six
kittens, one in the normal position in the uterus, and the other five
in the abdominal cavity. The foetal envelopes of the abdominal
embryos were attached by a sort of placenta to the parietal peritoneum
and to the omentum, and one had also an extensive attachment to the
fundus of the stomach. According to Webster2 ectopic pregnancy
always originates as tubal pregnancy, the tube subsequently under-
going rupture. Huffman 3 explains extra-uterine pregnancy as due
to an embedding in anomalous, but specialised tissues, arising from
a rudimentary second uterus or other accessory reproductive organs.
Tubal pregnancy is generally believed to be due to inflammatory
trouble which interferes in some way with the downward movement
of the fertilised ovum,4 but Loeb and Hunter5 state that in the
guinea-pig it is impossible to bring about tubal pregnancy through
a mere retention of the ovum in the Fallopian tube.

Ovarian pregnancy is very rare, although well authenticated.

THE FORMATION OF THE CORPUS LUTEUM

After the discharge of the ovum from the ovary the ruptured
Graafian follicle undergoes a series of changes which result in the
formation of the structure known as the corpus luteum.

The fully formed corpus luteum consists of large cells containing
a yellow pigment, the luteal cells, separated from one another by an
anastomosis of connective tissue which is seen to branch inwards
from the surrounding ovarian stroma, and to form a central plug in
which there are no luteal cells. This connective tissue contains
numerous blood-vessels, so that the fully developed corpus luteum is
a highly vascular structure.

Three hypotheses have been put forward regarding the manner
of formation of the corpus luteum. That of Paterson,6 who supposed
it to be derived from the blood coagulum left in the cavity of the
Graafian follicle after its discharge, gained few or no adherents. The

1 Gofton, "Ectopic Gestation in a Cat," Royal Dick Coll. Mag., vol. i.,
1906.

2 Webster, Ectopic Pregnancy, New York, 1895.

3 Huffman, "A Theory of the Cause of Ectopic Pregnancy," Jour. Amer.
Med. Assoc., vol. Ixi., 1913.

4 Mall, On the Fate of the Human Embryo in Tubal Pregnancy, Carnegie
Institute (Washington) Pub. No. 221, Washington, 1915.

5 Loeb and Hunter, " Experiments concerning Extrauterine Pregnancy,"
Pennsylvania Med. Bull., 1908. For further references the above papers may
be consulted.

6 Paterson, "Observations on Corpora Lutea," Edinburgh Med. and Surg.
Jour., 1840.

138 THE PHYSIOLOGY OF REPRODUCTION

other two theories, those of von Baer l and Bischoff,2 on the other
hand, have each received considerable support.

Von Baer regarded the corpus luteum as an entirely connective
tissue structure, in the origin of which the follicular epithelium had
no share ; while Bischoff concluded that the luteal cells were formed
by the hypertrophy of the epithelial cells of the undischarged Graafian
follicle. Among the principal supporters of von Baer's view appear
the names of Leuckart, His, Kolliker, Slavjansky, Gegenbaur,
Benckiser, Schottltinder, and Minot. Those who have adopted the
alternative theory of Bischoff include Pfliiger, Waldeyer, Call and
Exner, Beigel and Schulin.3

To Sobotta4 belongs the credit of being the first to deal
systematically with the question, and, with the publication of his

•ih

FIG. 38. — Recently ruptured follicle of mouse. (From Sobotta.)

/e, Follicular epithelium or membrana granulosa (somewhat hypertrophied) ;
th, theca interna ; «., ingrowth from same.

papers on the corpus luteum in the mouse, the controversy entered
upon a new phase. In Sobotta's investigation the material employed
was collected upon a definite plan, the animals being killed at known
intervals after coition, in reference to the occurrence of which the
period of ovulation had been previously determined. In this way
there was obtained a large series of corpora lutea representing
successive stages of development. The investigation resulted in
confirming Bischoff s view that the luteal cells are the much hyper-
trophied epithelial cells of the undischarged follicle, the connective
tissue network being derived from the inner layer of the theca.

1 Von Baer, De Ovi Mammalium et Hominis Genesi Epistola, Lipsiae, 1827.

2 Bischoff, Entwickelungsgeschichte des Kanincheneies, Biuunschweig, 1842.

3 For an account of the older literature of the subject see Sobotta, " Uber
die Entstehung des Corpus Luteum der Saugethiere," Merkel and Bonnet's
Ergebnisse der Anat. u. Entwick., vol. viii., 1899.

4 Sobotta, "Uber die Bildung des Corpus Luteum bei der Maus," Anat.
Anz., vol. x., 1895 ; and Arch. f. Mikr. Anat., vol. xlvii., 1896.

CHANGES IN THE OVARY 139

Sobotta describes the outer theca as taking no share in the ingrowth,
while the theca interna is stated to become entirely spent in the
formation of the inter-epithelial anastomosis. The hypertrophy of
the epithelial cells is said to be of the nature of a simple enlargement,
unaccompanied by division.

Sobotta's conclusions in regard to the development of the corpus
luteum in the mouse were subsequently confirmed by him in a further
investigation carried out on similar lines on the corpus luteum in the
rabbit.1 Moreover, Stratz 2 published descriptions of certain stages
of corpus luteum formation in Tarsius, Tupaia, and Soreoc, and these
agree in essential particulars with those given by Sobotta; while
Honore,3 also working on the rabbit, differed only in concluding that

FIG. 39. — Early stage in formation of corpus luteum of mouse.
(From Sobotta.)

I, Developing luteal cells ; e, germinal epithelium.

the inter-epithelial network is derived in part from the theca externa,
and not exclusively from the theca interna, and that the latter is not
entirely exhausted by the ingrowth, some part of it still remaining
to form a layer within the outer theca in the fully formed corpus
luteum.

On the other hand, several investigators have expressed doubts
regarding Sobotta's conclusions, and some have adopted the theory
originally formulated by von Baer that the luteal cells arise from the
connective tissue sheath of the follicle, the follicular epithelium being
either entirely discharged along with the ovum or else being partially

1 Sobotta, "Uber die Bildung des Corpus Luteum beim Kaninchen," Aiiat.
Hefte, vol. viii., 1897.

2 Stratz, Der Geschlechtsreife Saiigetkiereierstock, Haag, 1898.

3 Honore, "Kecherches sur 1'Ovaire du Lapin," Arch, de SioL, vol. xvi.,
1900.

140 THE PHYSIOLOGY OF REPRODUCTION

discharged and partially degenerating in situ. Amongst those who
have adopted this view are Nagel,1 who investigated the human
corpus luteum ; Clark,2 who contributed an account of the formation
of the corpus luteum in the sow and in the human subject ; Doering,3
who also worked upon the sow, and claimed to have confirmed Clark's
account ; and Biihler,4 Wendeler,5 and Stockel,*5 who have examined
and described developing human corpora lutea. Moreover, His,7
Kolliker,8 and Paladino9 have reiterated their adherence to von
Baer's hypothesis since the publication of Sobotta's work.

It is remarkable, however, that none of the supporters of this
hypothesis appear to have examined the growing corpus luteum in

FIG. 40. — Late stage in formation of corpus luteum of mouse. (From
Sobotta.) Thecal ingrowths are numerous. The cavity of the
follicle is not yet filled in.

all its stages of development, while in the case of several of the
accounts it is not clear whether the structures described were not in

1 Nagel, "Die Weiblichen Geschlechtsorgane," Bardeleben's Handbuch der
Anatomic ties Menscken, vol. vii., Jena, 1896. " Uber neuere Arbeiten auf dem
Gebiete der Anatomic der weiblichen Geschlechtsorgane," Merkel and Bonnet's
Ergebnisse d. Anat. u. Entwick., vol. viii., 1899.

2 Clark, "Ursprung, Wachstum, und Ende des Corpus Luteum," Arch. f.
Anat. ^t. Phys., Anat. Abth., 1898 ; Johns Hopkins Hospital Reports, vol. vii.,
1899.

3 Doering, " Beitrag zur Streitfrage iiber die Bildung des Corpus Luteum,"
Anat. Anz., vol. xvi., 1899.

4 Biihler, " Entwickelungsstadien Menschlichen Corpora Lutea," Verhand.
d. Anat. tiesell., in Pavia, 1900.

5 Wendeler, Martin's Die Krankheiten der Eierstocke und Nebeneierstocke.

6 Stockel, " Ueber die Cystiche Degeneration der Ovarien bei Blasenmole,"
Sep. Abdnwk am der Festschrift fiir Fritsch.

7 His, Discussion, Verhand. d. Anat. Resell., in Tubingen, 1899.

8 Kolliker, "Ueber Corpora Lutea Atretica bei Saugethieren," Verhand. d.
Anat. Gesell., in Kiel, 1898.

9 Paladino, "Per la Dibuttata Questione sulla Esenza del Corpo Luteo,"
Anat. Am., vol. xviii., 1900.

CHANGES IN THE OVARY

141

reality atretic follicles — that is to say, follicles which had undergone
degenerative changes without ever being discharged. Thus, the
words used in a description given by Clark seem to indicate that
this author was dealing with the degenerative epithelial cells of an
atretic follicle. It seems not impossible also that the young human
" corpus luteum " described by Doering was a degenerate follicle ;
while Kolliker's opinion that the corpus luteum is an entirely
connective tissue structure appears to have been founded on the
assumption that the changes exhibited by discharged follicles and

FIG. 41. — Corpus luteum of mouse fully formed. (From Sobotta.) The luteal
tissue is vascularised and the central cavitv filled in with connective tissue.

retrogressive undischarged follicles are identical in character. It is
to be noted further that in the investigations of all those writers
who have upheld the connective tissue hypothesis, the ages of the
developing corpora lutea were unknown, the material having been
collected in no case by Sobotta's method of killing the animals at
successive intervals after coition.

In 1901, after the publication of the papers referred to above,
the present writer issued a preliminary account l of an experimental
inquiry upon the formation of the corpus luteum in the sheep. In
this inquiry the animals were killed at successive intervals after

1 Marshall, "Preliminary Communication on the CEstrous Cycle and the
Formation of the Corpus Luteum in the Sheep," Proc. Roy. 8oc., vol. Ixviii.,
1901. The full paper was afterwards published in the Phil. Trans., B.,
vol. cxcvi., 1903.

142 THE PHYSIOLOGY OF REPRODUCTION

coition, or (in cases where coition did not or was not known to occur)
after oestrus was observed. The result of this investigation was to
confirm Bischoff s hypothesis in all essential particulars. The sheep,
however, was found to present some differences from the mouse (as
investigated by Sobotta) in regard to the origin of the connective
tissue network of the corpus luteum, this being discovered to
originate partly from the theca externa, and not merely from the
theca interna. It was found also that the cells of the follicular
epithelium continued to undergo mitotic division after the rupture
of the follicle, but not with the same frequency as previously. The
theca interna was stated to become entirely spent in the growth
of the connective tissue network. Four days after cestrus the
discharged follicle was found to have acquired all the characteristics
of the fully developed corpus luteum, the luteal cells, as seen in
section, being at least six times as large as the original epithelial
cells.

In the same year as the publication of the paper referred to
above, on the sheep's corpus luteum, van der Stricht1 gave an
account of the discharged follicle in bats belonging to the genera
Vesperitgo, Vexpertilioy and Placbttis. This was also confirmatory of
the conclusion that the follicle-cells hypertrophy and give rise to
luteal cells, but mitotic division among these cells was also seen
to occur. Van der Stricht calls attention to the appearance of fatty
particles at a very early stage in the history of the luteal cells. A
point of greater importance is that van der Stricht found that,
whereas the majority of the luteal cells are derived from the
follicular epithelium, a certain relatively small proportion of them
are developed out of interstitial cells in the inner theca of the
connective tissue sheath. This observation lends additional interest
to Miss Lane- Clay pon's statement that the follicle and interstitial
cells have an identical origin, since both are derived from the
germinal epithelium, and pass through a similar series of changes.2

The structure of the ovary, and the cyclical changes which it
undergoes in the case of the " marsupial cat " (Dasynrm vi.rerrinns),
have been investigated by Sandes,3 who shows that the mode of

1 Van der Stricht, " La Eupture du Follicule Ovarique et l'Histog6nese du
Corps Jaime," C. It. de I'Assoc. des Anatomistes, 3rd Session, Lyon, 1901. "La
Ponte Ovarique, etc.," Bull, de I' A cad. Roy. de Medecine Belgique, 1901.

2 Marshall, " The Development of the Corpus Luteum : a Keview," tyttar.
Jour. Micr. Science, vol. xlix., 1905. Miss Lane-Claypon's discovery that the
follicular epithelial and interstitial cells are probably equipotential may
perhaps help to elucidate some of the discrepancies between the accounts by
various authors of the formation of the corpus luteum.

3 Sandes, " The Corpus Luteum of Dasyurus I'iverrinus," Proc. Linnean Soc.^
New South Wales, vol. xxviii., 1903. See also O'Donoghue, " Ueber die Corpoi-a
Lutea bei einigen Beuteltieren," Arch. f. ^fik^. Anat., vol. Ixxxiv., 1914.

CHANGES IN THE OVARY

H3

formation of the corpus luteum in Marsupials is essentially similar
to what it is in the Eutheria. The theca interna folliculi is shown
to be rudimentary in Dasyurus, a circumstance which rendered it
especially easy to follow the subsequent changes undergone by this
layer. Sandes describes the follicular epithelium as undergoing so

FIG. 42. — Discharged follicle of rabbit nineteen hours after coition, or
about nine hours after ovulation. The epithelial cells are in process
of hypertrophy and there is some ingrowth of connective tissue from
the theca. The place of rupture is widely open. Haemorrhage is
slight. Outside the follicle are old luteal cells of large size. (L. F.
Messel.)

great an hypertrophy prior to the thecal ingrowth as sometimes
almost to fill the cavity of the discharged follicle, so that there
could be no possibility of confusing the epithelial with the connective
tissue cells.1

The formation of the corpus luteum in the rabbit has been

1 Through the kindness of Professor J. P. Hill I have been permitted to
examine sections in his possession of the corpus luteum of the Monotreme
Ornithorhynchiis parado.rus. These sections show much hypertrophied and
apparently fully developed luteal cells, but no trace of any ingrowth from the
connective tissue wall of the corpus luteum.

144 THE PHYSIOLOGY OF REPRODUCTION

further studied by Cohn,1 while the same process in the marmot has
formed the subject of an investigation by Yolker.2 Both authors
agree in supporting Bischoff. Yolker finds that the theca externa
takes a share in the connective tissue ingrowth, while the theca
interna does not become exhausted in the process.

Jankowski,3 however, has arrived at totally different conclusions,
and adopts the view that the luteal cells are modified connective
tissue cells. The material employed in this research appears to
have consisted of a miscellaneous collection of sows' and guinea-pigs'
ovaries obtained without any attempt at systematic investigation, so
that the ages of the corpora lutea were unknown. Jankowski bases
his opinion largely on the appearance of cells resembling luteal cells
in the theca interna of the undischarged follicle. It would seem
possible that these were interstitial cells, and so probably potentially
equivalent to follicle-cells (as supposed on independent grounds by
van der Stricht and Miss Lane-Claypon). More recently Corner4
has come to the conclusion that in the sow the corpus luteum is
formed from both epithelium and theca interna.

Sobotta5 and Loeb6 have investigated the formation of the
corpus luteum in the guinea-pig, and find, contrary to Jankowski,
that it is substantially the same as in the mouse, the rabbit, and
the sheep. According to Robinson 7 the luteal cells are formed from
the follicular epithelial cells in the ferret.

The results of those investigators who agree in adopting Bischoffs

1 Cohn, "Zur Histologie und Histogenesis des Corpus Luteum und des
Interstitiellen Ovarialgewebes," Arch. f. Mikr. Anat., vol. Ixii., 1903. Schafer,
however, states that in the rabbit the epithelial cells are entirely extruded at
ovulation, the cavity becoming filled largely with blood-clot prior to ingrowth
from the connective tissue wall (Essentials of Histology, llth Edition, London,
1920). The present writer has reinvestigated the question and finds that the
epithelium is retained. The confusion may have arisen through mistaking
atrophic follicles for discharged ones (see p. 150).

8 Volker, "Uber die Histogenese Corporis Lutei bei den Ziesel (Spermo-
philus citillus)" Bull. Internat. A cad. Science (Medicine), Prague, 1904.

3 Jankowski, " Beitrag zur Entstehung des Corpus Luteum der Saugethiere,"
Arch. f. Mikr. Anat., vol. xliv., 1904. Williams (Obstetrics, New York, 1904)
takes up the same position as Jankowski, partly on the ground that " the
rnembrana granulosa presents extensive degenerative changes, and is usually
cast off in great part at the time of rupture," and partly because certain cells
of the theca interna come to resemble luteal cells prior to ovulation. The
former statement is far from proved, and the latter cannot be regarded a»
conclusive (see text). Cf. also Seitz, "Die Follikelatresie," Arch. f. Gyncik.,
vol. Ixxvii., 1906.

4 Corner, "On the Origin of the Corpus Luteum of the Sow," Amer. Jour.
Anat., vol. xxvi., 1919.

5 Sobotta, " Uber die Bildung des Corpus Luteum beim Meerschweinchen,"
Anat. Hefte, vol. xxxii., 1906.

6 Loeb (L.), " Uber die Entwicklung des Corpus Luteum beim Meer-
schweinchen," Anat. Am., vol. xxviii., 1906.

7 Robinson, " The Formation, Rupture, and Closure of Ovarian Follicles in
Ferrets," Trans. Roy. Hoc. Edin., vol. lii., 1918.

CHANGES IN THE OVARY 145

theory of the mode of formation of the corpus luteum may be
summarised as follows : The luteal cells represent the epithelial
cells of the undischarged Graafian follicle. These, after rupture,
undergo a great hypertrophy, which may be accompanied in the
earlier stages by mitotic division, but only to a relatively slight
extent (Ovis, Vesperugo, etc.). Meanwhile the thickness of the wall
of the discharged follicle is further increased by an ingrowth of
connective tissue, which eventually forms an anastomosis of cells,
generally fusiform in shape, between the hypertrophying follicular
epithelial cells. This connective tissue ingrowth is either derived
from the theca interna alone (Mus, Cavia, Tarsius, Tupaia, Sorex,
Dasyurus, Vesperugo, etc.), or it may arise from both the theca
iuterna and the theca externa (Lepus, Ovis, Spermopliilus). The
theca interna may become entirely spent in this process {Mus, Cavia,
Tarsius, Tupaia, Sorex, Ovis, Dasyurus), or certain strands of this
layer may still remain and line the outside edge of the follicle after
it has become transformed into a fully developed corpus luteum
(Lepus, Spermophilus, Vesperugo). In some animals the interstitial
cells of the theca interna may develop into luteal cells in just
the same manner as the follicular epithelial cells ( Vesperugo, etc.).
Tha cavity of the discharged follicle becomes filled in eventually
by the further ingrowth of connective tissue, which forms a central
plug.

The changes undergone by the discharged follicle have also been
studied in certain of the lower Vertebrates. Giacomini,1 who has
investigated the subject in birds, amphibians, and, more particularly,
Elasmobranch fishes, describes an hypertrophy of the follicular
epithelium consequent upon ovulation. The discharged follicle of
Myliobatis is described and figured as a glandular body in which
the enlarged epithelium is penetrated by an extensive ingrowth of
connective tissue and blood-vessels. Wallace2 gives a somewhat
similar account of the spent follicles in the fishes Zoarces and Spinax.
In the latter especially there is a pronounced hypertrophic enlarge-
ment of the follicle-cells, associated with thecal ingrowths arrayed
in a radial manner. Lucien3 has described corpora lutea in the
reptiles Anguis and Seps, in which there is a simple hypertrophy
of the follicular epithelium unaccompanied by mitotic division.
Similar structures in reptiles have also been observed by Mingazzini,4

1 Giacomini, " Contribute all' Istologia dell' Ovario dei Selaci," Ricerca Lab.
di Anat. Normale della Hoy. Univ. di Roma, vol. v., 1896.

2 Wallace (W.), "Observations on Ovarian Ova, etc.," Quar. Jour. Micr.
Science, vol. xlvii., 1903.

3 Lucien, " Note preliminaire sur les premieres Phases de la Formation des
Corps Jaune chez certains Keptiles," C. R. de Soc. de Bio/., vol. lv., 1903.

4 Mingazzini, "Corpi Lutei verie falsi da Eettili," Ricerca Lab. di Anat.
Normale della Roy. Univ. di Roma, vol. iii., 1893.

146 THE PHYSIOLOGY OF REPRODUCTION

who believes them to be identicat with mammalian corpora lutea.
It is noteworthy that the above-mentioned animals which show
luteal hypertrophy are all viviparous. On the other hand, Biihler,1
who investigated the ovaries of Cyclostomes and certain Teleosteans,
was unable to find any hypertrophy of the wall of the spent follicle,
and Cunningham,2 also writing on Teleosteans, arrived at the same
result as Biihler. According to Pearl and Boring,3 however, a corpus
luteum is formed in the ovary of the hen after ovulation and simply
from the theca interna. It contains a yellow, fatty substance similar
to that of the corpus luteum of the cow.

The mammalian corpus luteum may contain a central clot
composed of blood derived from the vessels of the follicular wall
which gave way at the time of ovulation. In this case the blood-
clot becomes gradually absorbed along with the remainder of the
liquor folliculi. On the other hand, there may be practically no
haemorrhage, or the discharged blood may be expelled to the exterior
of the ovary (with the greater part of the liquor), remaining as a
small clot upon the surface.4 It would seem probable that the
vessels burst as an effect of the released tension consequent upon
the rupture of the follicle ; but, as already mentioned, it has been
suggested that possibly the latter process may itself occur as the
result of the pouring out of blood into the cavity. During the early
stages of formation of the sheep's corpus luteum leucocytes of the
polymorph variety nave been observed in great abundance, but in
the later stages they disappear, some of them undergoing degenera-
tion. These leucocytes are not extravasated, but wander inwards
with the growing strands of connective tissue.5 Their occurrence
should probably be associated with the necessity to dispose of the
blood-clot when such is present.

The ingrowth of connective tissue commences a very short time
after ovulation, and in the sheep may be seen very distinctly as
early as in the seven-hour stage of development. Blood-vessels
are carried inwards with the connective tissue, and these undergo
multiplication, so that the corpus luteum is a highly vascular structure.

If the discharged ovum fails to become fertilised the corpus goes

1 Btihler, "Riickbildung der Eifollikel bei Wirbelthieren," Morph. Jahr.,
vol. xxx., 1902.

2 Cunningham (J. T.), " On the Histology of the Ovary and of the Ovarian
Ova in certain Marine Fishes," Qiiar. Jour. Micr. Science, vol. xl., 1897 ; Honnoites
and Heredity, London, 1920.

3 Pearl and Boring, Sex Studies : " The Corpus Luteum in the Ovary of
the Domestic Fowl," Amer. Jour Aiutt., vol. xxiii., 1918.

4 It is sometimes stated that the haemoglobin of the blood clot is trans-
formed into the yellow pigment (known as lutein) which gives the luteal cells
their characteristic colour ; but this is obviously incorrect, since there may lie
no blood-clot in the follicle, whereas the luteal cells always contain lutein.

6 Mai-shall, Phil. Trans., lw. dt.

CHANGES IN THE OVARY 147

on growing usually for only a short time and then degenerates, so
that, in the case of the human female, two months after ovulation
it is reduced to the condition of an insignificant cicatrix. Miller1
found that in man the beginning of menstruation coincided with
the degeneration of the corpus luteum. In polyrestrous animals
which ovulate spontaneously the organ is in process of reduction
at about the time of the next " heat " period, but two corpora
lutea of different ages have been observed in the same ovary. Thus
Corner2 finds that in the sow there is, during the sexual season,
a regular overlapping in the duration of these structures, and at
any oestrus after the second there are in the ovaries corpora lutea
in an advanced stage of degeneration, probably six weeks old, and
others, about three weeks old, in a much less retrogressive condition.
In Mammals which experience pseudo-pregnancy the corpus luteum
under that condition may persist for a considerable time, which
is as long, or nearly as long, as if pregnancy had occurred, but
Hammond has shown that in the rabbit, in which pseudo-pregnancy
only occurs under experimental conditions (see p. 101), the corpora
lutea in the later part of gestation are larger than those of pseudo-
pregnancy. If conception succeeds ovulation, the corpus luteum con-
tinues to increase in size until almost the middle of pregnancy, and in
the human female attains to a diameter of nearly an inch in length.

The large size of the completely developed corpus luteum is the
more remarkable in that it results to so large an extent from the
simple hypertrophy of certain of its constituent cells. The wonderful
property which these cells possess of enlarging within a very short
time of ovulation is seemingly without a parallel in the physiology
of the Vertebrata, and it becomes additionally interesting in view of
the almost certain fact that the cells, from which the luteal cells
develop, are derived, like the ova, from the original germinal
epithelium.

During the later part of pregnancy the corpus luteum becomes
reduced in size, the luteal cells degenerating, losing their . yellow
colour,, and eventually (at least in some cases) appearing to become
transformed into cells resembling, if not identical with, the ovarian
interstitial cells referred to above (see p. 114).3 At the end of
pregnancy the human corpus luteum has a diameter not exceeding
half an inch in length. In some animals at any rate (rats, etc. ; see
p. 149) it may persist during the beginning of the lactation period.

1 Miller, "Corpus Luteum, Menstruation, und Graviditat," Arch. f.
vol. ci., 1914.

2 Corner, " Cyclic Changes in the Ovaries and Uterus of the Sow," Carnegie
Institution Publication (Contributions to Embryology, No. 64), 1921.

3 Schafer, Essentials of Histology, 7th Edition, London, 1907. The similarity
between the luteal and interstitial cells has also been remarked upon by Allen,
Joe. n't.

148 THE PHYSIOLOGY OF REPRODUCTION

The characteristics of the corpus luteum at different stages of
pregnancy have been described by van der Stricht,1 Corner,2 and
others. At first the luteal cells contain a large quantity of fat or
lipoid which is epithelial in nature. This decreases, but at a later
stage there is a reappearance of fatty material due to senescence.
Before retrogression sets in there is a diversity in the character of
the cells, some showing considerable peripheral canalisation while
others show only endoplasm.3 According to Corner the corpus luteum

FIG. 43. — Section through old corpus luteum. (From Sellheim.)
C, Connective tissue ; L, luteal tissue.

of pregnancy is distinguished from that of ovulation by the more
regular and uniform morphology of the former, and the greater
infiltration of fat in the latter.

1 Van der Stricht, " Sur le processus de 1'excretion des glandes endocrines,"
Arch, de Biol., vol. xxvii., 1912-13. This paper deals with bats.

2 Corner, "The Corpus Luteum of Pregnancy, as it is in Swine," Contributions
to Embryology, Carnegie Institution, Washington, 1915. This paper goes into
great detail and gives numerous references.

3 See also Delestre, " Recherches sur le Follicle de Graaf et le Corps Jaune
de la Vache," Jour, de Fanat. et physiol. (etc.), vol. xlvi., 1910 ; Hegar, " Studien
zur Histogenese des Corpus Luteum und seiner Riickbildungsprodukte,"
Arch. f. Gyn., vol. xci., 1910 ; and Drips, " Studies on the Ovary of the
Spermophile, etc.," Amer. Jour. Anat., vol. xxv., 1919. The last paper describes
three phases (red granules, lipoid droplets, and regression).

CHANGES IN THE OVARY 149

In man the corpus luteum eventually loses its colour, becoming
converted into the so-called corpus albicans, after which ifc is described
as becoming merged into the connective tissue of the ovary.

The corpus luteum of pregnancy is sometimes distinguished from
the structure formed when pregnancy does not supervene after
ovulation, the latter being called the false corpus luteum,1 or corpus
luteum of menstruation ; but it is obvious that the two bodies are
identical in the early stages, and otherwise essentially similar.2
According to Ancel and Bouin,3 in animals like the rabbit, which do
not ovulate spontaneoiisly during oestrus, these two kinds of corpora
lutea are identical throughout. In such animals interstitial cells are
believed to replace functionally the "periodic corpus luteum."
Hammond,4 however, as just remarked, has shown that the two kinds
of corpora lutea in the rabbit are not identical in size, but that
the organs formed under experimental conditions (corpora lutea of
pseudo-pregnancy, see p. 101) do not become so large as the corpora
lutea of pregnancy.

Watson,5 and Long and Evans,6 have described a corpus luteum
of lactation in the rat, but Hammond states that a study of suckling
rabbits' ovaries does not confirm this, but that nevertheless the
corpora lutea may persist for some days after pregnancy terminates
(see below, p. 622).

The hypotheses which have been put forward regarding the
function of the corpus luteurn, and the possible part which this organ
plays in the metabolism of pregnancy, will be discussed at some
length in a future chapter. (For chemistry of corpus luteum see
p. 273.)

THE ATRETIC FOLLICLE

It has been already mentioned that the rabbit, the ferret, and
certain other animals do not necessarily ovulate during oestrus in the
absence of the male. The follicles, instead of bursting, undergo
degeneration (atresia) with their contained ova. Heape 7 has shown
that the congested vessels in the wall of the follicle may rupture and

1 Or corpus luteum spurium.

2 The retrogressive changes are similar in both kinds of corpora lutea.

3 Ancel and Bouin, " Sur les Homologies et la Significance des Glandes a
Secretion interne de 1'Ovaire," C. If. de la Soc. de Biol., vol. Ixvi., 1909.

4 Hammond, " On the Causes Responsible for the Developmental Progress
of the Mammary Glands in the Rabbit during the latter part of Pregnancy,"
Proc. Roy. Soc., B^ vol. Ixxxix., 1917. This author bases his statements on a
number of careful measurements which are duly recorded.

6 Watson (B. P.), "On the State of the Ovaries during Lactation," Proc.
Physiol. Soc., Jour, of Physiol., vol. xxxiv., 1906.

6 Long and Evans, " The CEstrous Cycle in the Rat, and other Studies in
the Physiology of Reproduction," Anat. Record, vol. xviii., 1920.

7 Heape, " Ovulation, etc.," Proc. Roy. Sot:, B., vol. Ixxvi., 1905.

150 THE PHYSIOLOGY OF REPRODUCTION

pour blood into the cavity, where it forms a clot surrounding the
degenerating ovum. The brilliant, suffused red appearance of many
of the rabbit's follicles during the early stages of degeneration is said
to result from internal bleeding. The first rush of blood into the
cavity washes away the epithelium from the wall of the follicle, at
the same time disintegrating the theca interna. This rupture of the
vessels must be interpreted as of the nature of an attempted
ovulation, since it apparently only takes place with mature follicles
which would have discharged had coition occurred. In other follicles
bleeding does not necessarily take place at all. In section the cavity
of the degenerate follicle appears, during the early stages, to be

-^-•-'•' •"-

Fia. 44. — Section through follicle in early stage of degeneration. (From
Sellheim.) The ovum and follicular epithelium are in process of atrophy.

bounded by the theca externa, while the ovum may be seen as a
shrunken object no longer enclosed by a discus proligerus.1 Heape 2
states that the contents of the follicle are gradually absorbed through
the agency of ingrowing parenchyma cells and leucocytes. The
cavity is eventually filled in by the ingrowth of normal ovarian tissue.
The following characteristics serve to distinguish the degenerate
or atretic follicle (sometimes called the corpus luteum atreticum)
from the true corpus luteum : (1) There is no indication of any
rupture to the exterior. (2) The ovum, being retained in the follicle,
loses its regularly circular shape, becomes shrivelled, and gradually
disappears altogether. (3) The follicular epithelium, instead of

1 Marshall, " The (Estrous Cycle in the Common Ferret," Quar. Jour. Micr.
Science, vol. xlviii., 1904.

2 Heape, lov. cit.

CHANGES IN THE OVARY 151

hypertrophying, degenerates, the chromatic substance at one stage
often appearing in the form of fine points in the cytoplasm, and
much smaller than nuclei. Subsequently the remains of the cells
become unrecognisable, finally disappearing altogether. (4) The
connective tissue wall does not proliferate to form a network among
the epithelial cells, and there is generally no ingrowth from the
thecse until the epithelial cells are in an advanced state of degenera-
tion or have altogether disappeared. The earliest indication of atretic
change is usually seen in the chromatolytic changes in the epithelium.
Afterwards the theca interna degenerates, and then the ovum and
zona pellucida.

It should be mentioned, however, that the presence of a degenerate
ovum cannot, by itself, be regarded as an absolute indication of
follicular atresia, since Sobotta1 has recorded instances of rupture
in the mouse and in the rabbit in which the ova were accidentally
retained within the cavity of the follicle, the latter nevertheless
forming an otherwise typical corpus luteum ; and van der Stricht 2
has described a similar case of retention in Veape-ntgo, in which part
of the follicle was degenerate while another part possessed the
characteristic structure of a corpus luteum.

Degeneration may set in at all stages in the development of a
follicle, and not merely in the fully formed follicle which has failed
to rupture. Loeb3 has described follicular atresia as being common
in guinea-pigs of less than six months old. Kingsbury 4 has described
profound degeneration of certain follicles as occurring just before
sexual maturity in the cat. Atrophic follicles which have reached or
almost reached maturity (in the rabbit) before undergoing degenera-
tion are characterised by a considerable internal haemorrhage.

The degenerative changes which such follicles pass through have
been studied in various Mammalia (chiefly rabbits, cavies, and other
Eodents) by Schulin,5 Flemming,0 Schottlander,7 Henneguy,8 Janosik,9

1 Sobotta, loc. cit.

2 Van der Stricht, Une Anonwtlie interessante de Formation de Corps Jaune,
Gand, 1901.

3 Loeb (L.), "tiber hypertrophische Vorgange bei der Follikelatresie," Arch,
f. Mikr. Anat., vol. Ixv., 1905.

4 Kingsbury, "The Morphogenesis of the Mammalian Ovary," A met: Jour,
of Anat., vol. xv., 1914.

6 Schulin, " Zur Morphologic des Ovariums," Arch. f. Mikr. Anat., vol. xix.,
1881.

6 Flemming, "Ueber die Bildung von Richtungsfiguren in Saugethieren
beim Untergang Graafschen FolHkel," Arch. f. Anat. u. Phys., Anat. Abth., 1885.

7 Schottlander, "Beitrag zur Kenntniss der Follikelatresie, etc.," Arch. f.
Mikr. Anat., vol. xxxvii., 1891. " Ueber den Graafschen Follikel, etc.," Arch,
f. Mikr. Anat., vol. xli., 1893.

8 Henneguy, " Recherches sur 1'Atresie des Follicules de Graaf, etc.," Jour,
de VAnat. et de la Phys., vol. xxx., 1894.

9 Janosik, "Die Atrophie der Follikel," Arch. f. Mikr. Anat., vol. xlviii.,
1896.

152

THE PHYSIOLOGY OF REPRODUCTION

Kolliker,1 van der Stricht,'2 Seitz,3 Loeb, and certain other writers,
whose results are for the most part in general agreement. The
degenerate follicle in the cow has been described by Delestre.4

Schulin, and also Janosik, appear to regard the follicular epithelial
cells as being converted into leucocytes, which they undoubtedly
resemble when undergoing degeneration. Flemming, on the other
hand, denies the existence of leucocytes, pointing out that none exist
in the theca, and Schottlander clearly distinguishes degenerating
epithelial cells from leucocytes.

--3

fev.

IS

FIG. 45. — Section through follicle in late stage of degeneration. (From
Sellheim.) The cavity is in process of being filled by an ingrowth of
tissue from the wall. The ovum has disappeared.

More recently, however, Dubuisson5 has stated that in the
sparrow the follicle-cells may multiply and act as phagocytes to

1 Kolliker, " Uber Corpora Lutea Atretica bei Saugethieren," Verhand. d.
Anat. (resell., in Kiel, 1898.

2 Van der Stricht, " L'Atresie Ovulaire, etc.," Verhand. d. Anat. Gesell., in
Bonn, 1901.

3 Seitz, "Die Follikelatresie wahrend der Schwangerschaft, etc.," Arch. }.
Gynak., vol. Ixxvii., 1906.

4 Delestre, loc. cit. See also Athias, "Les phenomenes de division de
1'ovule, etc.," Anat. Anz., vol. xxxiv., 1909; and Asimi, "Observations on
Follicular Atresia, etc.," Anat. Record,, vol. xviii., 1920.

6 Dubuisson, "Contribution a 1'Etude du Vitellus," Arch, de Zool. Expe'r.,
vol. v., 5th series, 1906.

CHANGES IN THE OVARY 153

the yolk of the degenerating ovum, which becomes filled with them.
Afterwards they are said to migrate, leaving nothing but connective
tissue which fills in the cavity of the follicle. A similar process is
described as occurring in certain reptiles. Perez 1 also has recorded
the phagocytic absorption of ova by follicle-cells in the ovary of
the fasting newt.

Schottlander 2 states that atresia can occur by fatty degeneration
as well as by chromatolysis.

Flernming and others have described nuclear spindles in the ova
of follicles in an early stage of atresia, thus showing that these had
reached maturity before degeneration set in.

Atretic follicles may shrivel up rapidly, or continue for a time
in a cystic condition. In the latter case the cavity remains filled
with fluid. Kolliker has shown that certain of the cells in the theca
interna of cystic follicles may undergo a process of hypertrophy ; and
the same fact has been noticed by Seitz, who calls these cells " theca
lutein cells " owing to their resemblance to the cells of the corpus
luteum. Seitz found these cells only during pregnancy. Leo Loeb 3
also says that in the rabbit the theca interna cells may enlarge
during atresia, becoming epithelioid and gland-like and that they
remain in this condition for some time.

Heape4 states that in the rabbit two kinds of degeneration
prevail. In the one kind the changes first affect the follicle and
then the ovum, as described above. In the other the ovum is first
affected and the follicle afterwards. Heape interprets the latter
change as evidence that the ovum is not capable of assimilating the
nourishment supplied to it.

Atresia is commonly stated to occur most frequently during
pregnancy, but it may occur at other times.5 Thus Sandes6 has
shown that in Dasyurus, as soon as the corpus luteum is formed,
the surrounding follicles which were previously in various stages
of active development begin to undergo atrophy. The process begins
in the follicles in closest proximity to the newly formed corpus luteurn,
and is continued during pregnancy in the other follicles in ever-
widening circles. Sandes suggests that this occurs as a result of
mechanical pressure due to the growth of the corpus luteum, or
is in some way effected by the internal secretion which the latter

1 Perez, " Sur la Resorption phagocytaire des Ovules, etc.," Proces- Verbaux
de la Soc. des Sciences de Bwdeaux, 1903.

2 Schottlander, loc. cit.

3 Loeb, "The Relation of the Ovary to the Uterus and Mammary Gland,"
Trans. Amer. Gyn. Soc.^ 1917.

4 Heape, loc. cit.

5 Marshall, " The CEstrous Cycle, etc., in the Sheep," Phil. Trans., B.,
vol. cxcvi., 1903.

6 Sandes, loc. cit.

154 THE PHYSIOLOGY OF REPRODUCTION

organ is supposed to elaborate. Heape l states that in the case of
the rabbit, if the buck is withheld from a doe during several con-
secutive cestrous periods, not merely the majority of the older follicles
degenerate, but also many of the younger ones, so that the animal
is liable to become sterile during the remainder of the breeding season.2
There can be little doubt that the more usual cause of degenera-
tion in immature follicles is lack of sufficient nutriment, or of
nutriment of the requisite kind. It is usually to be observed in
underfed animals, or in animals living' under unsuitable conditions,
but it also occurs in very fat animals. Ewart states that follicular
degeneration tends to occur in mares leading a semi-wild life in
winter.3 Probably it is least common in animals which are in a
good thriving condition, but further investigation is urgently needed
before these points can be decided.

SUPERFCETATION

In the majority of Mammals, as in Dasyurus, there can be little
doubt that the presence of the corpus luteum tends to produce
follicular degeneration, or at any rate to inhibit maturation. In
the mare, however, Ewart has shown that degeneration does not
generally take place during early pregnancy, so that if a mare aborts
(a common occurrence with this animal) ripe ova are available for
fertilisation, and pregnancy can be started anew without delay.4

If ovulation takes place during pregnancy, and if, owing to the
occurrence of coition (see p. 33), the ova become fertilised, the
phenomenon of superfoetation may take place — that is to say,
foetuses of different ages may be present in the same uterus — but
this condition is of course abnormal, though it has been known to
occur in several animals. Thus, Mr. W. O. Backhouse has informed
me of a case of a cat which experienced heat and underwent coition
after being pregnant for six weeks, and three weeks later produced
five kittens, four of which were of the normal size and were obviously
born at full time (dating from the heat period prior to the beginning
of pregnancy), whereas the other kitten was very small, and
apparently about three weeks developed.

Kuntz, however, has pointed out that the existence of fetuses of
varying sizes is not necessarily evidence of superfoetation, since the
smaller foetuses may be atrophic.5

1 Heape, loc. cit.

2 Of. Dubreuil and Regaud (C. R. de la Soc. de Bid., vol. Ixvii., 1909), who
say that absence of sexual intercourse causes haemorrhage in the follicles.

3 Ewart, loc. cit.

4 Ibid.

5 Kuntz, " Retention of Dead Foetuses in Utero and its Bearing on the
Problems of Superfcetation," Anat. Record, vol. xviii., 1920. Cf. Hammond,
see below, Chapter XIV., p. 657.

CHANGES IN THE OVARY 155

FORMATION OF OVA

It is usually stated that all the ova which are to be developed in
the ovary exist in it at the time of birth, and that a considerable
proportion of these undergo atrophy before puberty. Thus, the
number of ova in the ovary at birth has been estimated at 100,000,
of which it is supposed that not more than 30,000 remain at puberty.1
Miss Lane-Claypon,2 however, has described the formation of ova,
resembling primordial ova, from interstitial cells during adult life.
These cells are shown to increase markedly in size, their length being
often almost doubled. In addition to their becoming enlarged,
certain of the interstitial cells near the periphery undergo further
changes during the later stages of pregnancy. The cells appear to
pass outwards and become cut off by connective tissue, and in many
cases almost reach the surface of the ovary. This process begins in
the rabbit at about the twentieth day of pregnancy. A little later
some of the cells appear to be multi-nucleated, and it is suggested
that these are formed by the fusion of the same number of interstitial
cells as there are nuclei. The nuclei then degenerate with the
exception of one, and the inference is drawn that the latter lives and
grows at the expense of the others in just the same way as Balfour
concluded that one developing ovum in the immature ovary might
be nourished by the surrounding ova which were undergoing
degeneration.

In the ovary of a rabbit whose time of parturition had nearly
arrived, the interstitial cells were observed to have undergone
further changes identical with those taking place in the deutobroque
cells of a young ovary during the period of oogenesis (see above,
p. 116). The leptotenic stage is rapidly passed through and the
nucleus enters upon the synaptenic condition, which extends over a
somewhat longer time. The massing of the chromatin into a lump
having been completed, it again becomes spread out and rearranged,
and the pachytenic stage is entered upon. The chromatin filaments
during this stage are markedly thicker and more bulky. It is
followed by a not very typical diplotenic stage, in which the duality
of the filaments is said to be not well shown. In the'next stage —
the dictyate stage — the nucleolus becomes very definite, and the
chromatin is arranged more or less over the entire nuclear area,
which is now of considerable dimensions. " There can be ... not

1 Galabin, A Manual of Midwifery, 6th Edition, London, 1904. According
to another calculation the human ovary at the age of seventeen contains 17,600
ova (Heyse, Arch. f. (j-yncik., vol. liii., 1893), of which only 400 become mature
(Heine, Handlnich der Anatomic, 1873).

2 Lane-Claypon, " On the Origin and Life-History of the Interstitial Cells in
the Ovary in the Babbit," Proc. Roy. Soc., B., vol. Ixxvii., 1905.

156 THE PHYSIOLOGY OF REPRODUCTION

much doubt that the changes taking place are identical with those
seen in the young ovary, which lead to ovogenesis, and therefore it
would appear that ovogenesis also takes place in the adult animal
during pregnancy." l

Thus it would seem that the interstitial cells, which, like the ova,
are almost certainly derived from the germinal epithelium, are
actually potential ova, being capable of developing into true ova
when the appropriate stimulus is given. This stimulus is provided
by pregnancy, at which period they undergo enlargement so as to
exceed the size of a primordial ovum, and in addition pass through
the same series of nuclear transformations as those which characterise
embryonic oogenesis.2

THE SIGNIFICANCE OF THE PROCESTROUS CHANGES

Having discussed the conditions under which the Graafian follicles
ripen and discharge in various species of the class Mammalia, we are
now in a position to consider more fully the significance of the uterine
changes with which ovulation is frequently associated.

Many obstetricians have adopted the view that the degeneration
stage of menstruation in the human female is of the nature of an
undoing of a preparation (represented by the previous growth stage)
for an ovum which failed to become fertilised (or even to be released
from the ovary). This theory was originally put forward by
Sigismund,3 and was subsequently .accepted by His.4 It has been
summarised in the well-known dictum that " women menstruate
because they do not conceive." It has been shown above, however,
that menstruation in the Primates is the physiological homologue of
the prooestrum in the lower Mammalia, and that ovulation in the
latter occurs usually, so far as is known, during oestrus, or at any
rate not until after the commencement of the destruction stage of
the prooestrum. Consequently Sigismund's theory becomes untenable.

It is possible, however, that in man the breaking-down stage
represents pseudo- pregnant degeneration as well as prooestrous
destruction owing to the two processes having become telescoped into
one another as a consequence of the shortening of the cycle, while, as
Hammond points out, the uterine congestion in the rabbit is greatest
at the end of pseudo-pregnancy and just before the onset of a new
ccstrous period. In the monoestrous dog, however, prooestrous
destruction and pseudo-pregnant degeneration are distinct.

1 Lane-Claypon, lor. fit.

- Cesa-Bianchi (loc. cit.) comments on the close resemblance between luteal
and interstitial cells.

3 Sigismund, " Ideen iiber das Wesen der Menstruation," Berliner Klin.
Wochenschr., 1871.

4 His, Anatomic Menschlicher Embrt/onen, 1880.

CHANGES IN THE- OVARY 157

Loewenthal l advanced the somewhat different theory that the
monthly bleeding is actually brought about by the death of the
ovum in the uterus, the " decidua " of menstruation being produced
by the embedding therein of the unfertilised egg. No evidence has
been adduced in support of this view, which is evidently open to the
same objection as Sigismund's hypothesis.

A further modification of the same theory has been advanced by
Beard,2 who expresses the belief that the process of menstruation is
of the nature of an " abortion of something prepared for an .egg given
off at or after the close of the preceding menstruation, and [that] it
takes place because this egg has escaped fertilisation." "Prior to
the appearance of the menses the uterus has formed a decidua,
which is regarded as equivalent to that which woulcl arise when a
fertilised egg became affixed to the uterus." This theory also, if it
is to be entertained at all, necessitates the assumption that there is
no correspondence between the prooestrum in the lower Mammalia
and menstruation in the Primates, since the degeneration stage of
the prooestrum in the dog or ferret, for instance, can hardly be of the
nature of an abortion of something prepared for an ovum which was
discharged at the preceding "heat period" many months before.
The difficulty is further increased for those animals which experience
oestrus only once a year, or even less often, for it is improbable that
they ovulate more frequently than they come "on heat." Beard,
however, denies that there is any correspondence between " the heat
or rut of mammals " and menstruation in the higher forms, saying
that very little is required in disproof of the supposed relation.

The theory that the whole prooestrous process, including both
the degeneration and the recuperation stages, is of the nature of a
preparation 3 on the part of the uterus for the reception of a fertilised
ovum is not opposed to any of the known facts. The process is
sometimes viewed as a kind of surgical " freshening " of the uterus,
whereby the ovum can be safely attached to the mucosa during the
healing stage. It is possible, however, that the changing • of the
uterine tissue is not the least important part of the process.

Emrys-Eoberts 4 has made the further suggestion that the secre-
tion of the uterine glands, together with the blood and other products

1 Loewenthal, "Eine neue Deutung des Menstruationsprocesses," Arch. f.
Gyncik., vol. xxiv., 1884.

2 Beard, The Span of Gestation and the Cause of Birth, Jena, 1 897.

3 Kundrat and Engelmann, " Untersuchungen iiber die Uterusschleiruhaut,"
Strieker's Med. Jahr., 1873. Lawson Tait, Diseases of Women, 1889. For a
further discussion of some of the theories regarding the pur-pose of menstruation,
see Heape, "The Menstruation of Semnopithecus entellus" Phil. Trans., B.,
vol. clxxxv., 1894.

4 Emrys-Roberts, 'fcA Preliminary Note upon the Question of the Nutrition
of the Early Embryo," Proc. Roy. Soc., B., vol. Ixxvi., 1905.

i5« THE PHYSIOLOGY OF REPRODUCTION

of prooestrous destruction, may serve to provide a rich pabulum on
which to nourish the embryo during the earliest days of pregnancy.

In opposition to these theories it may be urged that pregnancy
has been known to take place in women who have never menstruated,
and that it may occur during periods of amenorrhoea, or during the
lactation period, when menstruation is sometimes in abeyance. Such
cases, however, are the exception, and it must not be inferred that,
because the prooestrous function can occasionally be dispensed with
without inducing a condition of sterility, it normally plays no part
in the physiology of generation.

It has been pointed out, however, that the severity of the
menstrual process in woman is occasionally so great as to be
pobitively injurious, and that such cases evidently belong to the
category of constitutional disharmonies which Metchnikoff1 has
shown to be so common in the organs and functions of the generative
system.

Geddes and Thomson 2 also have called attention to the patho-
logical character of menstruation, as evidenced not only by the pain
which frequently accompanies the process, and the local and con-
stitutional disorders by which it is often attended, but by the general
systemic disturbance which always occurs synchronously with it.
These authors interpret the discharge as a means of disposing of
the anabolic surplus which is consumed during pregnancy by the
developing embryo. A similar view is adopted by Webster,3 who
associates the introduction of menstruation (as distinguished from
the prooestrum of the lower animals) with a diminished fertility.

Reference has already been made to the " Wellenbewegung " or
" wave " hypothesis regarding the nature of menstruation (see p. 6 1).4

The physiological cause of the prooestrum, and the probable part
played by the ovaries in this connection, will be discussed at some
length in a later chapter.

1 Metchnikoff, The Nature of Man, London, 1903.

2 Geddes and Thomson, The Evolution of Sex, Revised Edition, London, 1901.

3 Webster, "The Biological Basis of Menstruation," Montreal Med. Jour.,
April 1897.

4 The cyclical changes in the size of the ovaries are referred to on pp. 22 and
53 (footnote).

CHAPTER V
SPERMATOGENESIS— INSEMINATION

" Semper enim partus duplici de semine constat." — LUCRETIUS.

THE spermatozoa, or reproductive cells of the male, were observed
as far back as the year 1677, when Hamm, who was a pupil of
Leeuwenhoek, directed the latter's attention to them. Leeuwenhoek,
however, did not understand the significance of what he saw.

Spallanzani1 was the first to show that the presence of sper-
matozoa in the semen was an essential factor in fertilisation, since
the filtered fluid was found to be impotent. Subsequently Kolliker 2
discovered that the sperms arise from the cells of the testis, and
Barry3 observed the conjugation of sperm and ovum in the rabbit.

Van Beneden's discovery that the nuclei of the conjugating cells
— both ova and spermatozoa — contain only half the number of
chromosomes that they had originally has been referred to in the
preceding chapter, where the maturation phenomena in the ovum
have been briefly outlined4 (p. 125). The four products of division
formed at the completion of reduction in the male differ from those
in the female in that each of them is a functional conjugating cell.
Before describing the reduction process in detail it will be well to
give a short account of the structure of the testis.5

This organ is enclosed within a fibrous capsule, the tunica
albuginea, which is very rich in lymphatics. It is covered by a
layer of serous epithelium reflected from the tunica vaginalis.
Posteriorly the capsule is prolonged into the interior of the testis
in the form of a mass of fibrous tissue (the mediastinum testis).
Certain other fibrous processes or trabeculje also project inwards
from the capsule, and divide the glandular substance into lobules.
The efferent ducts of the testis (vasa efferentia) open into a single

1 Spallanzani, Dissertations, English Translation, vol. ii., London, 1784.

2 Kolliker, Beitrdge zur Kenntniss der Geschlechtsverhaltnisse, etc., Berlin, 1841.

3 Barry (M.), " Spermatozoa observed within the Mammiferous Ovum,"
Phil. Trans., 1843.

4 For accounts of the history of the chief discoveries relating to the
spermatozoa, fertilisation, etc., see Thomson, The Science of Life, London,
1899, and Geddes and Thomson, The Evolution of Sex, 2nd Edition, London,
1901.

5 See Barry (D. T.), "The Morphology of the Testis," Jour, of Anat. and
Phi/s., vol. xliv., 1910.

1.9

160 THE PHYSIOLOGY OF REPRODUCTION

convoluted tube situated at the posterior margin of the organ and
attached to the mediastinum. This is the epididymis. Its lower
extremity is prolonged into a thick-walled muscular tube (the vas
deferens) which is the passage of exit for the seminal fluid or
sperm-containing secretion. The glandular substance of the testis
is composed of the convoluted seminiferous tubules, two or three
of which join together to form a straight tubule which passes into

FIG. 46. — Section through human testis and epididymis. (After Bohm
and von Davidoff, from Schafer.)

a, Glandular substance divided into lobules by septa of connective tissue ;
6, tunica albuginea ; <?, part of epididymis ; d, rete testis ; e, body of
epididymis ; /, mediastinum ; g, sections through commencing portion
of vas deferens.

the body of the mediastinum. The straight tubules within the
mediastinum unite in their turn, giving rise to a network of vessels
called the rete testis. From the rete the vasa efferentia are given
off. Between the tubules is a loose connective tissue containing
a number of yellow epithelioid interstitial cells. The connective
tissue also contains numerous lymphatics and blood-vessels (branches
of the spermatic artery). The nerves of the testis are derived from
the sympathetic system, but a few filaments come from the hypo-
gastric plexus.

SPERMATOGENESIS— INSEMINATION

161

In embryonic development the tubules arise from the primitive
germinal epithelium. According to Allen l the interstitial cells are
derived from connective tissue.

The straight tubules, and the tubules of the rete, are lined by a

d

-s

FIG. 47. — Section through testis of monkey.

a, Seminiferous tubules ; 6, interstitial tissue ; c, rete testis ; d, vasa
efferentia ; e, vas deferens ; /, tunica albuginea.

single layer of cubical or flattened epithelium without a basement-
membrane. The seminiferous tubules, on the other hand, contain
several layers of epithelial cells supported by a thick basement-

1 Allen, "The Embryonic Development of the Ovary and Testis," Amer.
Jour, of Anat., vol. iii., 1904. As already mentioned, Allen regards the inter-
stitial cells of the ovary as being developed from connective tissue, thus differing
from Miss Lane-Claypon.

6

1 62

membrane.1 The layer nearest the membrane consists of clear
cubical cells, a few of which show evidence of division. These are
the spermatogonia. Certain of the epithelial cells between the
spermatogonia are enlarged, and project among the more internal
cells in association with developing sperms. These are the cells of

FIG. 48. — Section through portion of two seminiferous tubules in testis of rat.

a, Basement-membrane ; b, spermatogonium ; • o, spermatocyte ; rf, sper-
matozoa in cavity of tubule ; e, interstitial tissue containing vessels.

Sertoli. On the inside of the spermatogonia are certain larger cells,
known as spermatocytes. These are products of division of sper-
matogonia, each of which on dividing into two gives rise to a cell
like itself, and another cell, which grows larger, passes into the
second layer, and becomes a spermatocyte.

The spermatids, which in some seminiferous tubules lie on the

1 Curtis, "The Morphology of the Mammalian Seminiferous Tubule," Amer.
Jovr. of Anat., vol. xxiv., 1918.

SPERMATOGENESIS— INSEMINATION 163

inside of the spermatocytes, are the double products of division of
the latter. The spermatids so formed may be seen as small cells
with spherical nuclei, and forming irregular clumps on the inner
surface of the tubule. Often, however, the spermatids are elongated,
being partially converted into spermatozoa. As this .process of
transformation proceeds, the developing sperms become arranged in
little groups. Associated with each group is a foot-cell, or a cell
of Sertoli, which probably serves as a support and as a means of
conveying nourishment to the growing spermatozoa.1 The tails of
the latter at this stage project freely into the cavity of the tubule,
and a little later the spermatozoa shift bodily forward and become
completely liberated. According to Loisel,2 the orientation of the
sperms in the testis is due to a secretion from the cells of Sertoli,
together with certain of the other cells in the parietal layer of the
seminiferous epithelium.

FIG. 49. — A cell of Sertoli with which the spermatids (three of which are
shown) are beginning tq be connected — human. (After Bramman, from
Schafer.) The cell contains globules j>f nutritive substance, and similar
smaller globules are seen in the spermatids.

In male animals which have a rutting season spermatogenesis
occurs only at this time. At other seasons of the year the testes
remain in a quiescent condition. The periodic activity of the testis
is usually correlated with a great increase in the size of that organ
(see pp. 22 and 55). In the hedgehog the interstitial cells have
been shown to proliferate even more than the spermatogenetic tissue,
the seminiferous tubules becoming widely separated.3 The same, fact
has been observed in the woodchuck 4 after hibernation, and in the
spring and summer. As with the hedgehog the interstitial hyper-
trophy is followed by regression with the approach of autumn.

1 Merkel, "Die Stiitzzellen des Menschlichen Hodens," Mutter's Arc/iiv, 1871.
Brown, "On Spermatogenesis in the Rat," Quar. Jour. Micr. Science, vol. xxv.,
1885. Bende, " Untersuchungen iiber den Bau und Funktioniren des Samen-
kanalchens einiger Saugethiere," Arch. f. Mikr. Anat., vol. xxx., 1887.

2 Loisel, " Facteurs de la Forme et de la Fasciculisation des Spermies dans
les Testicules," Jour, de I' Anat. et de la Phys., vol. xlii., 1906.

3 Marshall, " The Male Generative Cycle in the Hedgehog," Jour, of Physiol.,
vol. xliii., 1911. Similar changes occur in the mole. See Tandler and Gross,
Die Biologischen Grundlagen der Sekimddren Geschlechtscharaktere, Berlin, 1913.

4 Rasmussen, " Seasonal Changes in the Interstitial Cells of the Testis in the
Woodchuck," Amer. Jour, of Anat,, vol. xxii., 1917.

164 THE PHYSIOLOGY OF REPRODUCTION

In some animals the renewal of activity in the teates is associated
with the descent of these organs from their position in the abdominal
cavity through the inguinal canal and into a cutaneous fold.1 This

FIG. 50. — Diagram illustrating the cycle of phases in spermatogenesis.
(From Schafer.)

«, Spermatogonia (seen dividing at 6) ; a', a", Sertoli cells ; 6, spermatocytes
(seen dividing at 5) ; c, spermatids ; s', parts of spermatids which dis-
appear when spermatozoa are fully formed ; s, seminal granules.

1 Berry Hart, " The Nature and Cause of the Physiological Descent of the
Testes," Jour, of Anat. and Phys., vol. xliv., 1910. The author sums up the
essence of the process as follows : " The testis is united to a mammary area,
at first by the testicular caudal ligament and the inguinal fold or gubernaculum.
The developing gubernaculum, with the aid of the cremaster and peritoneum,
forms a pit or fossa for the testis in the Rodentia ; a more complete canal or
more or less pendulous scrotum in higher mammals. By subsequent dis-
proportionate growth of canal and testes, and finally (according to Frank) by
the involution and shrinkage of the gubernaculum, the testes in man become
permanently lodged in the scrotum." Numerous references to literature are
appended to this paper. When, as sometimes happens in man, one or both
of the testes do not descend or only imperfectly descend, the condition is said
to be one of cryptorchism. In cryptorchids spermatogenesis usually only takes
place for a short time after puberty (one or two years), if at all, and then the
seminiferous tissue degenerates, but the interstitial cells remain. Crew has
suggested that the aspermatic state of such testicles is due to the greater
temperature within the body as compared with the scrotum, and that the final
stages of spermatogenesis are inhibited by the higher temperature ("A
Suggestion as to the Aspermatic Condition, etc." Jour, of Anat., vol. Ixvi., 1922).
Guyer has made another suggestion, based on his work with spermatotoxic sera

SPERMATOGENESIS— INSEMINATION

165

is transformed into the scrotum, which lies behind the penis (except
in Marsupials, where it is in front). In many Mammals the descent
takes place at an early age and is permanent. In others (most

Spermatogonium.

Oogonium.

Proliferation
period.

Growth period.

Maturation
period.

FIG. 51. — Scheme of spermatogenesis and oogenesis. (After Boveri.)

Kodents, Insectivores, and bats) the testes are withdrawn into the
abdominal cavity after the breeding season is over. This is effected
by the cremaster muscle. In Monotremes, Edentates, Cetacea, and
Proboscidea there is no descent.1

prepared by repeatedly injecting fowls with sperms of rabbits ; the sera are
stated to be toxic for sperms of rabbits and guinea-pigs when injected into the
blood at intervals for four or five weeks, pmrtial or complete sterility resulting,
the spermatogenetic tissue degenerating (" Studies on Cytolysins," III., Jour, of
Exp. Zool., vol. xxxv., 1922). Kuntz had found that after ligation of the vas
deferens in the rat the seminiferous tissue degenerated in both testes, and it is
suggested by Guyer that this result may have been due to spermatotoxins
resulting from resorption (Kuntz, Anat. ftec., vol. xvii., 1919). Kuntz's result is
not confirmed by other observers, and Guyer's suggestion seems very unlikely
on general grounds.

1 Woodland has put forward a theory of the descent of the mammalian
testes involving the inheritance of acquired characters. His view is that the
descent has been caused by the action of mechanical strains resulting in rupture
of the attachments, such strains being due to the inertia of the organs (which
are larger than the ovaries of the female) reacting to the " impulsiveness "
(e.g. leaping or galloping movements) involved in the activity of the animals
(Proc. Zool. Soc., 1903). Cunningham (J. T.), who adopts this view, points out
that the descent takes place in the foetus and is related to the general habits
which begin soon after birth, and not to sexual habits (Hormones and Heredity,
London, 1921).

166 THE PHYSIOLOGY OF REPRODUCTION

The changes which occur in spermatogenesis may be summarised
as follows: (1) A spennatogoniurn divides into two, one product of
division passing into the second layer of the seminal epithelium
and becoming a spermatocyte. (2) A primary spermatocyte, or
mother-cell, divides, the number of chromosomes becoming reduced
during this process to one-half the previous number. (3) A secondary
spermatocyte so formed divides, giving rise to a spermatid. Sub-
sequently the spermatid elongates, the nucleus becomes shifted to
one end, and the spermatozoon which is formed in this way is set
free. The process is continually going on in the seminiferous tubules
of the testis, successive crops of spermatozoa being from time to
time produced. The various stages of development may generally
be observed in the same testis, or even within the limits of a single
tubule.1

It is supposed that the reduction in the number of the chromo-
somes is a preparation of the conjugating cells for their subsequent
union in fertilisation, and is a means by which this number is held
constant in the species (see p. 126).2 In those animals in which
reproduction is normally effected without the intervention of a
spermatozoon (parthenogenesis) the ovum may discharge only one
polar body instead of two.

STRUCTURE OF SPERMATOZOA

A fully developed human spermatozoon consists of a flattened
egg-shaped head, a short cylindrical body or middle-piece, and a long
delicate vibratile tail. Lying anterior to the head is a small apical
body, or achrosome, which in some animals bears a little barb-like
projection by means of which the spermatozoon bores its way into
the ovum. The tail of the sperm consists of an axial filament
surrounded by a protoplasmic envelope, which becomes very thin or
disappears altogether at the extremity, leaving a short naked end-
piece. The axial filament passes anteriorly through the middle-piece,
and ends in a small knob (the end-knob) at the base of the head.

1 The process of reduction may result in two sorts of spermatozoa being
produced, these after fertilisation giving rise respectively to the two sexes, in
whose body cells the chromosomes may differ in number or in kind ; that is to
say, one sex may carry two chromosomes specially associated with sex and called
the " X chromosomes," while the other sex only carries one X chromosome, with
or without another smaller chromosome called the " Y chromosome " (see
Chapter XV. below).

2 For an account of the process of spermatogenesis in different animals and
plants, and a discussion of the phenomena described, see Wilson (E. B.), The Cell
in. Development and Inheritance, 2nd Edition, London, 1900. In this work the
theories of Weisinann and others are dealt with, and a full account of the
literature is given up to 1900. For later work see Doncaster, An Introduction
to the Stud)/ of Cytology, Cambridge, 1920.

SPERMATOGENESIS— INSEMINATION

167

Ballowitz1 has shown that the axial filament is composed of a
number of parallel fibrilla1, like a muscular fibre.

Schweigger - Seidel 2 and
La Valette St. George 3 were
the first to prove, independ-
ently but almost simultane-
ously, that the spermatozoon
has the essential character-
istics of a complete cell. The
head contains the nuclear
material, which is sur-
rounded by a thin layer of
cytoplasm. The end-knob is
said to represent the centro-
some.

Spermatozoa, conforming
with more or less closeness
to the type described above,
occur in the great majority
of multicellular animals from
the Ccelenterata up to Mam-
mals. In Pisces, and also in
Echinoderms, the general re-
semblance is very distinct,
but in other forms of life
there is more diversity in
the shape assumed by the
spermatozoa. "The head
(nucleus) may be spherical,
lance-shaped, rod-shaped,
spirally twisted, hook-shaped,
hood-shaped, or drawn out
into a long filament; and it
is often divided into an an-
terior or a posterior piece of

different staining capacity,
as is the case with many
birds and Mammals. The
achrosome sometimes appears

FIG. 52. — Human spermatozoa 011 the tiat
and in profile. (After Bramman, from
Schafer.) x 2500. Those on the right
have adhering protoplasm. The tail is
only partly shown in the two seen in
profile.

1 Ballowitz, " Untersuchungen iiber die Struktur der Spermatozoen," Arch,
f. Mikr. Anat., vol. xxxii., 1888, and vol. xxxvi., 1890 ; Zeitsch. f. wiss. Zool.,
vol. lx., 1890, and vol. Ixii., 1891.

2 Schweigger-Seidel, " Uber die Samenkorperchen und ihre Entwickelung,"
Arch.f. Mikr. Anat., vol. i., 1865.

3 La Valette St. George, " Uber die Genese der Samenkb'rper," Arch, f. Mikr.
Anat., vol. i., 1865.

1 68

THE PHYSIOLOGY OF REPRODUCTION

to be wanting, e.g. in some fishes. When present, it is sometimes a
minute rounded knob, sometimes a sharp stylet, and in some cases
terminates in a sharp barb-spur by which the spermatozoon appears
to penetrate the ovum (Triton}" l The middle-piece also shows
considerable variability. It may be spherical, cylindrical, or flattened
against the nucleus ; sometimes it is of great length, and sometimes
it passes insensibly into the nagellum or tail. The latter, in
some insects and fishes, gives attachment to a membranous fin.
The end of the axial filament, as already mentioned,
is sometimes left naked, giving rise to the end-piece.
The tadpole-like shape is not an essential char-
acteristic of the spermatozoon, for in certain Arthro-
pods and Nematodes there is no flagellum, and the
sperms are consequently incapable of spontaneous
movement. In the daphnid Polyphemus the sperms
are said to be amoeboid. In some crustacean sper-
matozoa there are a number of radiating spine-like
processes which seem to take the place of the
flagellum.

In other animals, and notably in the gasteropod
mollusc Paludina, there are two kinds of sper-
matozoa. In this animal one is of the usual type,
whereas the other is larger and worm-shaped, with a
tuft of cilia at one end. The smaller variety alone

FIG. 53.

Human sperma-
tozoa ( x 1000). is said to be functional.2

(After Retzius,
from Scliafer.)

distinct part by
Retzius.

The size of the sperm varies greatly in different
animals. In man its length is about '05 millimetre
tlie or a 300th of an inch, the head and the middle-
flat ; b, head ; piece being each about '005 millimetre long.

. j j| .

tr,miaaie-piece; jj. -g odious that the sperm contributes com-

d, tail; e, end-

piece of tail, paratively little material to the fertilised ovum,

described as a being provided with only sufficient protoplasmic
substance to form a locomotive apparatus by means
of which it gains access to the ovum. The pre-
dominantly destructive metabolism of the spermatozoon as con-
trasted with the ovum has been strongly emphasised by Geddes

1 Wilson, loc. cit.

2 For further details of the structure of various kinds of sperms see Wilson,
loc. cit. ; also Ballowitz's papers just referred to, and Retzius' Biologisclie
Untersuchungen, vols. xi., xii., and xiii., Stockholm and Jena. The latter
contains numerous large plates with figures of spermatozoa. For sexual
differences .in sperms (numbers of chromosomes, etc.), see Chapter XIII. See
also von Winiwarter, Arch, de Biol., vol. xxvii., 1912 (man) ; Wodsedalek, Biol.
Bull., vol. xxv., 1913 (pig) ; vol. xxvii., 1914 (horse) ; Leplat, Arch, de Biol.,
vol. xxv., 1910 (cat) ; Painter, Jour. Exp. Zool., vol. xxxv., 1922 (opossum);
Guyer, Biol. Bull., vol. xxi., 1916 (fowl) ; and Swift, Amer. Jour, of Anat.,
vol. xx., 1916 (fowl). See also references on p. 128 above.

SPERM ATOGENESIS— INSEMINATION

r69

and Thomson,1 who believe it to exemplify those katabolic pheno-
mena which, according to their view, are usually associated with the
male sex.

a

d

FIG. 54. — Different forms of spermatozoa from different species of
animals, as follows : —

«, Bat ; 6 and c, frog ; rf, finch ; e, ram ; /'and #, boar ; h, jelly-fish ;
«', monkey ; £, round worm ; I, crab. (From Verworn.)

SEMINAL FLUID

The semen serves as the mechanical medium in which the
spermatozoa move. It is possible also that it has a nutritive function.
It is secreted by the seminiferous tubules. It is milky in appearance,
and has a characteristic smell. When ejected the seminal fluid is
mixed with the secretions of the accessory glands (prostate, etc.),
which render it still more milky. On standing it tends to become
gelatinous. According to Lode,2 the specific gravity of semen is
between 1*027 and T046.

The number of spermatozoa which exist in normal human semen
is subject to much variation. Lode 3 has shown that it diminishes
almost to zero after a number of successive emissions, but increases
again after an interval of several days. The average number is
given as 60,000 per cubic centimetre. The number of sperms
present in the ejected seminal fluid of the dog was also found to
be greater at the end of an interval in which there were no emissions,
but it did not continue to increase after more than eight or ten days.
In a normal emission of semen (man) Lode calculates that there are

1 Geddes and Thomson, The Evolution of Sex, Revised Edition, London, 1901.

2 Lode, " Untersuchungen iiber die Zahlen- und Regenerationsverhaltnisse
der Spermatozoiden bei Hund und Mensch," Pfliiger's Arch., vol. 1., 1891.

3 Lode calculates that about 339,385,500,000 spermatozoa must be produced
in man between the ages of twenty-five and fifty-five.

6 A

1 70 THE PHYSIOLOGY OF REPRODUCTION

about 226,000,000 spermatozoa, but that the number may vary from
zero to 551,000,000.

Lloyd-Jones and Hays l have investigated the effects of excessive
sexual activity upon the semen and offspring of rabbits. They found
that the semen becomes less viscous and the spermatozoa less
numerous while their motility is somewhat reduced also. The
percentage of pregnancies induced by the services becomes less as
the number of previous services increases, but the sizes of litters
actually born do not appear to be reduced until after the fifteenth
copulation. The offspring themselves were not affected, except
possibly in regard to sex (see below, Chapter XIV., p. 637).

The spermatozoa which are not ejaculated degenerate. The tails
break off, and undergo a gradual liquefaction. The end products are
ultimately absorbed by the epithelial cells of the seminal vesicles,
and perhaps by the cells of the vasa deferentia or of the testis itself.
According to Perez,2 the spermatozoa of male newts which are kept
apart from females are absorbed by phagocytes.3

MOVEMENTS OF SPEKMATOZOA

When the spermatozoa are in the testis they are inactive, but
they begin to move rapidly as soon as they are ejected in the seminal
fluid. The rate at which they progress has been estimated at 3'6
millimetres per minute.4 Bischoff5 found spermatozoa at the top
of the oviduct in the rabbit nine or ten hours after coition.

It is probable that the ejected spermatozoa continue to undergo
movement, as a general rule, so long as they retain their vitality, the
rate of movement becoming gradually diminished and ceasing
altogether shortly before death. In bats, however, during the
period of hibernation the sperms become quiescent without dying,
their vigour being restored in the spring when they conjugate with
the ova.6 It is exceedingly probable also that in the spotted
viviparous salamander and the -other animals referred to below

1 Lloyd-Jones and Hays, "The Influence of Excessive Sexual Activity of
Male Eabbits," I. and II., Jour, of Exp. Zool., vol. xxv., 1918. Cf. Amantea,
"Recherches sur la Secretion Spermatique," Arch. Ital. de Biol., vols. Ixii. to
Ixiv., 1914-16.

2 Perez, " Resorption phagocytaire des Spermatozo'ides," Proces- Verbaux de
la Soc. des Sciences de Bordeaux, 1904.

3 For chemistry of the spermatozoon and semen, see Chapter VIII.

4 Lott, Anatomic und Physiologic des Cervix Uteri, Erlangen, 1871. According
to Adolphi ("Ueber das Verhalten von Schlungenspermien in stromender
Flussigkeiten," Annt.Anz., vol. xxix., 1906), the spermatozoa of the adder swim
at the rate of 50 fj- to 80 M per second.

5 Bischoff, Die Entwickelung des Kaninchen-Eies, Giessen, 1842.

6 See p. 131.

SPERMATOGENESIS— INSEMINATION 171

(p. 178), in which the male cells retain their vitality for long
periods, these must at such times remain quiescent, for otherwise
their store of energy would soon become exhausted.

The spermatozoa swim by means of their tails. The movement
is represented in the accompanying figure (taken from Nagel),1
which shows the successive positions assumed by the sperm in a
state of locomotion. A wave of movement first makes its appearance
in the forepart of the tail, and then rapidly travels backwards to
the end, to be succeeded by a fresh wave which follows the same
course. It would seem that the driving force is located a little
behind the head. The head itself does not appear to be concerned
in the movements of locomotion.

The movements of spermatozoa have probably been studied most
closely in Insecta and Echinodermata. Buller2 says that the
sperms of the Echinoidea in a drop of sea-water (or the medium in
which they are normally discharged) swim spirally, so long as they

FIG. 55. — Diagram illustrating wave-like movement of swimming
spermatozoon. (From Nagel.)

do not come into contact with the surface. The spirals may be so
steep that the sperms appear to move almost in a straight line, in
which case progression across the field of the microscope is relatively
rapid. In other cases the incline of the spiral is so slight that the
spermatozoa swim almost in circles, and consequently move forward
across the microscopic field with great slowness. Every gradation
between these two extremes was observed but the more active
sperms generally swam in the steeper spirals.

Dewitz 3 has shown that when the spermatozoa of the cockroach
are put into 0'6 per cent, solution of sodium chloride, and placed
between two surfaces, such as those of a slide and a cover-glass, they
collect after a short time, partly upon the upper surface of the slide

1 Nagel, Handbuch der Pkysiologie des Menschen, vol. ii., Braunschweig, 1906.

2 Buller, " Is Chemotaxis a Factor in the Fertilisation of the Eggs of
Animals?" Quar. Jour. Micr. Science, vol. xlvi., 1902.

. 3 Dewitz, "Ueber Gesetzmassigkeit in der Ortsveranderung der Sper-
matozoen, etc.,'J Pfliiger's Arckiv, vol. xxxviii., 1886. Rotation by spermatozoa
seems to have been recorded first by Eimer, " Untersuchungen iiber den
Bau und die Bewegung der Samenfaden," Verhand. d. Pkys. Med. Gesel. zur

Wiirzburg, vol. vi, 1874.

i/2 THE PHYSIOLOGY OF REPRODUCTION

and partly upon the lower surface of the cover-glass. In these
positions they describe circles with their tails, the rotation being
invariably counter-clockwise. The bulk of the liquid remains free
from spermatozoa, the latter adhering to the glass surfaces after
having once reached them. If a ball be placed in the fluid, its
surface is soon sought by the spermatozoa.1 Verworn has described
this phenomenon under the name of " barotaxis," and states that it
is caused by pressure acting unequally on different sides of the
spermatozoon. It is said to be of great importance in the process of
fertilisation, and probably assists the spermatozoon in entering the
micropyle of the ovum.2 Dewitz's observations were subsequently
confirmed by Ballowitz.3

Counter-clockwise rotation upon surfaces was first recorded for
the spermatozoa of Echinoderms by Dungern,4 who discovered the
phenomenon in Sphcerechinus and Arbacia. About the same time
Buller,5 who has described the manner of rotation more fully,
observed its occurrence in the sperms of various other Echinoderms,
and particularly in those of Echinus : " When a spermatozoon comes
in contact with a glass surface, unless it becomes immediately fixed
to the glass [it] begins to make characteristic circular revolutions
upon it. If the cover-glass be supported by pieces of another cover-
glass, and the upper surface of the drop in contact with it be carefully
focused, it is seen that all the spermatozoa which are not attached
by their heads, but are moving there, are revolving from the
observer's point of view in clockwise direction. If the lower surface
of the drop in contact with the slide be examined, a reverse rotation
— the counter-clockwise — is seen to be the rule. In both cases,
therefore, if the surfaces be regarded from the point of view of the
spermatozoa, the rotation is always in one direction — namely, the
counter-clockwise."

The head is the only visible part of the rotating spermatozoon.
This moves rapidly round in a circle, which in the case of Echinus is
slightly less than 0'05 millimetre (or the length of a spermatozoon)
in diameter. A normally rotating sperm of Sphcerechinus was
observed to make 109 circles around one point in ninety seconds.
The rate of movement of the head is calculated to be about 0'12
millimetre per second, or 7'2 millimetres per minute.

The characteristic rotation may likewise take place upon surfaces

1 Ballowitz, " Untersuchungen iiber die Struktur der Spermatozoon, etc.,"
ZeitscLf. Zool., vol. i., 1890.

2 Verworn, General Physiology, Lee's Translation from the second German
Edition, London, 1899.

3 Ballowitz, loc. cit.

4 Dungern, "Die Ursachen der Specietat bei der Befruchtung," Zentralbl.f.
PhysioL, vol. xv., 1901.

6 Buller, loc. cit.

SPERMATOGENESIS— INSEMINATION 173

which are bounded by air (instead of glass), and it has been observed
also upon the outer surface of the gelatinous layer of the ova of
Echinus. Buller concludes, therefore, that the nature of the surface
is not an important factor in the process.

Ballowitz expresses the opinion that the circles described by
insects' sperms are simply the modified spirals made by the free-
swimming cells. Buller thinks that this view, which provides a
purely mechanical explanation, is also probably correct for the
spermatozoa of Echinoderms.

Since counter-clockwise rotation upon surfaces has been observed
in the spermatozoa of two groups as widely separate as the Insecta
and the Echinoderrnata, it would seem probable, as Buller remarks,
that it will be found to occur in other animals.

The spermatozoa of Mammals, in traversing the female passages
after copulation, make their way upward towards the ovaries in
opposition to downward currents set up by the cilia of the lining
epithelia. Kraft l has shown that when rabbits' spermatozoa, in a
state of feeble motion, are placed upon the inner wall of the oviduct
their movements become more vigorous and they swim against the
current which the cilia produce. Roth 2 also has succeeded in
experimentally illustrating the same fact.

It is commonly stated that in man the passage of the spermatozoa
from the vagina inwards is assisted by a contraction of the muscular
wall of the uterus, which compresses the cavity of that organ into
which the sperms are drawn when relaxation takes place.3 The
contraction of the uterus is said to be a reflex action resulting from
copulation. It has also been suggested that, during copulation, a
mucous plug which is ordinarily contained in the cervix may be
temporarily and partially expelled into the vagina and afterwards
withdrawn with the spermatozoa adhering to it.4

So also Heape 5 has shown that in the rabbit the passage of the
spermatozoa into the uterus is probably assisted by a sucking action
on the part of the latter organ. The os uteri, which is situated
above the ventral wall of the vagina, was observed to dip down
into the seminal fluid at the bottom of the vagina, and then to be
withdrawn again in conjunction with a peristaltic contraction of the

1 Kraft, " Zur Physiologic des Flimmerepithels bei Wirbelthieren," Pfliiger's
Arckiv, vol. xlvii., 1890.

2 Both, " Ueber das Verhalten beweglicher Mikroorganismen in stromender
Fliissigkeit," Deutsche med. WocJiensckrift, vol. xix., 1893. Verworn (loc. cit.)
describes this property of spermatozoa under the name of rheotaxis, which, he
says, is a special kind of barotaxis. See also Adolphi, " Die Spermatozoon der
Saugethiere schwimmen gegen den Strom," Anat. Anz., vol. xxvi., 1905.

3 See Beck, " How do the Spermatozoa enter the Uterus ? " Amer. Jour, of
Obstet., vol. viii., 1875.

4 See Williams, Obstetrics, New York, 1904.

5 Heape, "The Artificial Insemination of Mares," Veterinarian, 1898.

174 THE PHYSIOLOGY OF REPRODUCTION

uterus. These movements were repeated at intervals. Moreover,
it was found that the sucking action could be induced artificially by
stimulating the erectile tissue of the vulva. It is probable, however,
that the spermatozoa, after once entering the uterus, proceed to their
destination unassisted, and that the direction of their movement is
determined by the capacity they possess to respond to the stimuli
set up by opposing currents. Moreover, pregnancy has been known
to follow imperfect coition in man, so that there can be no doubt
that under certain circumstances the spermatozoa are capable of
passing inward by their own unaided efforts.1

INSEMINATION

The act of copulation results in the introduction of seminal fluid
through the generative aperture of the female. The mechanism by
which this is effected in the higher animals is described in a future
chapter, where the functions of the accessory male organs are dealt
with. The introduction of the fluid into the female generative
passages is known as insemination (as distinguished from impregna-
tion, which is the term used in reference to the female when
fertilisation takes place2).

It is obvious that in those animals which ovulate spontaneously
during the oastrus periods it should be possible to induce pregnancy
at such times by the artificial introduction of spermatozoa into the
vagina or into the uterus. That this could actually be effected was
probably first demonstrated by Spallanzani,3 though there is evidence
that the practice of artificial insemination was not unknown to
the Arabs many centuries ago.4 The following is a description of
Spallanzani's original experiment, as quoted from a contemporary
English translation : —

" I chose a bitch spaniel of moderate size which had before had
whelps. Suspecting, from certain appearances, that she would soon
be in heat, I confined her in an apartment, where she continued a
long time, as will be seen below. For greater security, that she
might never be let loose, I fed her myself, and kept the key the
whole time. On the thirteenth day she began to show evident signs

1 For further information regarding the passage and fate of the spermatozoa
in the female body, see Kohlbrugge, "Die Verbreitung der Spermatozoviden
im Weiblichen Korper, etc.," Arch. f. Entwick., vol. xxxv., 1912.

2 That is to say, the animal is inseminated when the spermatozoa are intro-
duced, and it is impregnated when the ovum becomes fertilised by a sperm.
See Heape, " The Artificial Insemination of Mammals," Proc. Roy. Soc., vol. Ixi.,
1897.

3 Spallanzani, Dissertations, vol. ii., London, 1784.

4 Gautier, Le Fecondation artificielle, etc., Paris, 1889.

SPERMATOGENESIS— INSEMINATION 175

of being in heat ; the external parts of generation were tumid, and a
thin stream of blood flowed from them. On the twenty-third day
she seemed fit for the admission of the male, and I attempted to
fecundate her artificially in the following manner. A young dog of
the same breed furnished me, by a spontaneous emission, with
nineteen grains of seed, which were immediately injected into the
matrix, by means of a small syringe introduced into the vagina. As
the natural heat of the seed of animals of warm blood may be a
condition necessary to render fecundation efficacious, I had taken
care to give the syringe the degree of heat which man and dogs are
found to possess, which is about 30° [or between 99° and 100° F.].
Two days after the injection, the bitch went off her heat, and in
twenty days her belly appeared swollen, which induced me to set
her at liberty on the twenty-sixth. Meanwhile the swelling of the
belly increased ; and sixty-two days after the injection of the seed,
the bitch brought forth three lively whelps, two male and one
female, resembling in colour and shape not the bitch only, but the
dog also from which the seed had been taken. Thus did I succeed
in fecundating this quadruped ; and I can truly say, that I never
received greater pleasure upon any occasion, since I first cultivated
experimental philosophy."

Spallanzani also records a similar experiment by Pierre Rossi, in
which a dog was impregnated by artificial means.

Considerable success has been obtained in recent years in experi-
ments on the artificial insemination of dogs. Gautier l refers to a
case in which pregnancy was induced by this means. Albrecht2 and
Plonuis3 have also described experiments in which they successfully
inseminated dogs by artificial methods (see p. 649). Heape4 has
recorded a series of experiments carried out by Sir Everett Millais
on the artificial insemination of Basset hounds. The present writer
has succeeded in inducing pregnancy by this method in a Dandie
Dinmont terrier. Moreover, there are numerous cases on record in
which dogs have been successfully inseminated artificially as a means
of overcoming certain forms of barrenness (see p. 649). The method
adopted in all these experiments was substantially the same as that
employed by Spallanzani.

Artificial insemination is now also practised on mares, donkeys,
and cows, and usually with the object of remedying sterility. In
thoroughbred mares especially it has proved of great service, having

1 Gautier, loc,. tit.

2 Albrecht, " Kiinstliche Befruchtung," Woc/tensc/ir. /. Thierheilkunde und
Viehzucht, Jahrg. xxxix.

3 Plonnis, " Kiinstliche Befruchtung einer Hiinden, etc.," Inaug. Dissert.,
Rostock, 1876.

4 Heape, loc. tit.

176 THE PHYSIOLOGY OF REPRODUCTION

been the means of preserving for breeding purposes many valuable
animals which otherwise would have been discarded.1

Iwanoff2 has described experiments in which pregnancy was
induced in rabbits and guinea-pigs by the artificial injection of
testicular fluid into the female generative passages. The same
investigator states that he induced hybridisation between a male rat
and a female mouse by artificially inseminating the latter (see p. 649,
Chapter XIV.).

He has shown, further, that the spermatozoa retain their vitality
sufficiently long to admit of their being employed successfully in
artificial insemination if they are kept in solutions of various salts
(sodium chloride, sodium carbonate, etc.) or in serum instead of in
the secretions of the accessory generative glands. Hunter appears
to have been the first to practise artificial insemination upon a
woman (previously sterile),3 but it has since been successfully
adopted by various medical men, the method being to inject the
spermatozoa through the os into the cavity of the uterus
(see p. 647).

With those animals whose ova are normally fertilised outside the
body, artificial insemination is a still simpler process. Spallanzani
was the first to show that the eggs of various species of Amphibia
could be fertilised by the application of fluid obtained from the
testes or seminal vesicles of the male, and that the frogs and newts
which were generated by this means in no way differed from those
produced in nature. Spallanzani was also successful in artificially
fecundating the eggs of the silk-worm moth.

Artificial impregnation of fish ova was first employed by Jacobi,4
and the method which he adopted is practically the same as that
habitually practised at the present day for stocking water-courses
with fish.

The vitality of the spermatozoon appears to vary widely in the
different species of animals.

1 For references to particular experiments see Heape, "The Artificial
Insemination of Mares," Veterinarian, 1898 ; also a booklet published by
Huish (The Cause and Remedy of Sterility in Mares, Cows, and Bitclies,
London, 4th Edition, 1899), in which a large number of cases are described
in which artificial insemination was successfully carried out ; also Iwanoff,
"De la Fecondation Artificielle chez les Mammiferes," Arch, des Sciences
Biologiques, vol. xii., 1907. The last-mentioned paper contains an account
of a very large series of experiments on horses, cows, and sheep, with a
full description of the practical methods employed, and a very complete
account of the literature of the subject.

2 Iwanoff, " La Fonction des Vesicules seminales, etc.," Jour, de Phys. et de
Path, gen., vol. ii., 1900.

3 See Home, " An Account of the Dissection of an Hermaphrodite Dog,"
Phil. Trans., 1799.

4 See Giinther, Introduction to the Study of Fishes, Fxiinburgh, 1880.

SPERMATOGENESIS— INSEMINATION 177

Leeuwenhoek,1 and subsequently Prevost and Dumas,1 state that
they found moving sperms in the internal genital organs of female
rabbits and dogs eight days after coition. Bonnet 2 says that he
observed motionless sperms, which, therefore, were probably dead,
but had not yet undergone disintegration, in a bitch seventeen and a
half days after coition. In a series of experiments upon the
longevity of the spermatozoon in the rabbit, it was found that these
cells can survive in the vasa deferentia for at least ten days after
the removal of the testes, but that they die before the end of
thirteen days.3

Spallanzani4 stated that a hen can lay fertilised eggs twenty
days after impregnation, but it would appear that there is some varia-
tion. Elford r> states that a drop in the fertility of the eggs takes
place on the ninth day, that 50 per cent, of the eggs are fertile on
the tenth day, 16 per cent, on the fifteenth, and after that none at
all. Philips6 and Kaupp7 have made confirmatory observations.
The first fertile egg in fowls is said to be laid three or four days after
mating. In the turkey one insemination is sufficient to fertilise a
whole batch of eggs. Riddle 8 found the sperms of the ring-dove
retained their fertilising power for nearly eight days.

Strassmann9 has recorded a case in which human spermatozoa
survived in the female generative passages for a week after coition.
Bossi 10 refers to a similar instance where the sperms lived for over
twelve days. In another case described by Diihrssen,11 living
spermatozoa were found, in a woman who stated that coition had
not been experienced for three and a half weeks.

In many species of bats, as already mentioned, copulation takes
place in autumn and ovulation in the following spring, so that the
spermatozoa retain their vitality while stored up in the uterus
during the hibernating period. Sperms obtained from the females

1 See Waldeyer's article in Hertwig's Handbuch der Entwicklungslehre,
Jena, 1903.

2 Bonnet, "Giebt es bei Wirbelthieren Parthenogenesis," Merkel und
Bonnet's Ergebnisse d. Anat. u. Entwick., vol. ix., 1900.

3 Marshall and Jolly, "Contributions to the Physiology of Mammalian
Reproduction : The (Estrous Cycle in the Dog," Phil. Trans., B., vol. cxcviii.,
1905.

4 Spallanzani, loc. cit.

5 Elford, Canada Exp. Farms Report, 1916.

6 Philips, Jour. A'mer. Assoc. Instr. and Invest. Poultry Husbandry, 1918.

7 Kaupp, North Canadian Exp. Stat. Bull., 1915.

8 Riddle and Behre, " Studies on the Physiology of Reproduction in Birds :
IX. On the Relation of Stale Sperm to Fertility and Sex in Ring-doves,"
Amer. Jour, of Physiol., vol. Ivii., 1921.

9 Strassmann, Lehrbuch der gerichtlichen Medizin, 1895.

10 Bossi, "Etude Clinique et Experimentale de 1'Epoque la plus favorable
a la Fecondation de la Femme," Rivista di Obstet. e Ginecol., 1891.

11 Diihrssen, "Lebendige Spermatozoon in der Tube," Centralbl. f. Gyndk.,
1893.

1 78 THE PHYSIOLOGY OF REPRODUCTION

at this time are dormant, but regain their vitality on the application
of warmth.1

The spermatozoa of some warm-blooded animals will stand
considerable variation in temperature and still retain their vitality.
Thus they have been known to live for many hours at ordinary
room temperature ; but cold, while it reduces their motility, tends
to prolong their life, the motility being regained under a higher
temperature. Heape states that some seminal fluid of a dog was
sent to him by post in a glass tube, and on being examined eighteen
hours after it was obtained, fully half the spermatozoa were found
to be active and vigorous, while increased warmth stimulated to
activity those which showed signs of sluggishness but did not revive
the remainder.

Chelchowski,2 in describing the methods adopted in the artificial
insemination of mares, lays stress upon the necessity of keeping the
seminal fluid warm, and states that, if this is done, it is possible to
keep the sperms alive for twenty hours ; but it is possible that
Chelchowski may have mistaken absence of movement under a low
temperature for death.

The experimental work of Wolf and of other recent investigators
is described below in the chapter on fertility (p. 650).

The case of bats, which has been referred to above, has a parallel
in certain cold-blooded animals. Thus, according to liollinat,3 in
snakes belonging to the species Tropidonotus viperinus the females
are usually inseminated in the autumn, whereas the eggs are not
laid until the beginning of the following summer. Also in the case
of the spotted viviparous salamander (Salamander maculosa), after
the birth of the young, which occurs about the month of May, a
new batch of ova pass into the oviducts and are fertilised (prior to
the commencement of the sexual season) by spermatozoa which
were introduced in the July of the previous year, and thereafter
stored in the uterus.4 It is obvious that in both these cases the
spermatozoa retain their vitality in the female for periods of many
months.

In animals like the earthworm, in which the spermatozoa are
stored in special reservoirs known as spermathecai, it is probable
that they retain their vitality for long periods. Lang5 has shown

1 See Eimer and other references given on p. 131.

2 Chelchowski, Die Sterilitat des Pferdes, Wien, 1894. See also Lewis, "The
Vitality of Reproductive Cells," Bull. 90, Agric. Exper. Stat., Oklahoma, 1911.

3 Rollinat, " Sur 1'Accouplement des Ophidiens a la Fin de FEte et au
Commencement de 1'Automne," Bull. Zool. Soc. France, vol. xxiii., 1898.

4 Sedgwick, Student's Text-Book of Zoology, vol. ii., London, 1905.

5 Lang, " tTber Vorversuche zu Untersuchungen iiber die Varietaten-
bildungen von Helix hortemis Miiller and Helix nemoralis L.," Festschr. sum
siebzigsten Geburtstage von Ernst Haeckel, Jena, 1904.

SPERM ATOGENESIS— INSEMINATION 179

that the sperms may live for three years in the vesiculse seminales
of snails.

The extreme longevity possessed by the male cells of some insects

is still more remarkable. Von Siebold l states that the spermatozoa

of bees may survive for four or five years. Moreover, queen ants

have been known to lay fertile ova thirteen years after the last

1 intercourse with a male.

1 Von Siebold, " Fernere Beobachtungen iiber die Spermatozoen Wirbelloser
Tiere," Mutter's Archiv, 1837.

FERTILISATION x

" Although it be a known thing subscribed by all, that the fostus assumes
its origin and birth from the male and female, and consequently that the egge
is produced by the cock and henne, and the chicken out of the egge, yet neither
the schools of physicians nor Aristotle's discerning brain have disclosed the
manner how the cock and its seed doth mint and coine the chicken out of the
egge." — HARVEY.

ALTHOUGH much progress has been effected, and many new facts
have been discovered, since Harvey wrote his famous dissertation
on " The Efficient Cause of the Chicken," the actual nature of the
process whereby the ovum, after being discharged from the ovary,
is endowed with a new vitality through union with a sper-
matozoon, is a problem the solution of which is still far from
complete.

In 184:3 Martin Barry,'2 as already mentioned, first observed the
union of the spermatozoon and ovum in the rabbit, and a little later
Newport 3 recorded its occurrence in the frog ; but it was not until
the last quarter of the nineteenth century that the significance of
the process was realised. It was largely through the work of
Hertwig, Strasburger, and van Beneden that most biologists came
to believe that the union of the nuclei of the gametes was the
essential act in the process of conjugation. The more recent
investigations of Boveri and others do not, however, entirely support
this conclusion.

As already described, the head of the spermatozoon represents
the nucleus, and contains the chromatin material. When the sperm
penetrates into the substance of the ovum the tail becomes absorbed,
but the head remains as the male pronucleus. The matured nucleus
of the ovum, or female pronucleus (the two polar bodies having
been discharged), passes towards the centre of the cell, where it
unites with the male pronucleus which generally becomes somewhat
enlarged. The middle-piece of the spermatozoon also enters the egg,

1 Revised, with numerous additions, by Cresswell Shearer.

2 Barry, "Spermatozoa Observed within the Mammiferous Ovum," Phil.
Trans., 1843.

3 Newport, "On the Impregnation of the Ovum in the Amphibia," Phil.
Trans., 1851.

180

FERTILISATION

181

and, according to Boveri,1 induces the formation of a centrosome,
which, after the completion of fertilisation, initiates the process of
cell division. Cytoplasmic filaments arrange themselves around the
centrosome in the form of a star, the sperm-aster, which accompanies
the male pronucleus, and afterwards comes to lie alongside of the
segmentation nucleus (as the nucleus- formed by the union of the
two pronuclei is called). In the segmentation nucleus the normal

FIG. 56. — Successive stages in the fertilisation of an ovum of Echinus
S, showing the entrance of the spermatozoon. (From Bryce.)

number of chromosomes characteristic of the species is once more
restored. The oosperm, or zygote, produced in this way is the
starting-point of a long series of cell divisions which culminate in
the formation of a new, completely developed individual.

1 Boveri, Zelleti Studien IV., Ueber die Natur der Centrosomen, Jena, 1901.
Jenkinson, "Observations on the Maturation and Fertilisation of the Egg of
the Axolotl," Quar. Jour. Micr. Science, vol. xlviii., 1904, has recently stated
that the middle-piece of the spermatozoon, after forming the centre of the
sperm-sphere and sperm-aster, completely disappears, and that the centrosome
is formed from the sperm-nucleus at a later stage. (The sperm-sphere is the
clear area which forms in the ovum round the head and middle-piece of the
spermatozoon shortly after its entrance.)

182 THE PHYSIOLOGY OF REPRODUCTION

Jenkinson, who has carried out a series of experiments intended
to elucidate the physical processes occurring in fertilisation, draws
the conclusion that the structures which appear in the ovum are
produced under the influence of the middle-piece and centrosome.
He supposes these bodies to possess the power of withdrawing water
from the cytoplasm, of swelling up and dissolving in the water so
absorbed, and then giving off radial outgrowths which precipitate
the proteins of the cell, and so produce the fertilisation spindle.
Jenkinson lays some stress on the fact that a watery fluid collects in
vacuoles in the centre of the sperm-sphere of the axolotl, and regards
the presence of this fluid as evidence that the sperm introduces a
hydroscopic substance into the ovum. In confirmation of this the

FIG. 57. — Three stages in the conjugation of male and female nucleus
in the fertilisation process of Echinus. (From Bryce.)

experiments show that a hydroscopic particle is capable of giving
rise to an astral structure in a colloid solution.1

Boveri and others have proved experimentally that portions of
unfertilised Echinoderm ova, without egg nuclei, may develop
normally after the addition of spermatozoa, while Driesch has
shown that if such ova are deprived of their envelopes by shaking,
and are then divided into fragments some of which contain no
nuclei, the latter are capable of being fertilised a second time. It
is clear, therefore, that in such cases the union of nuclei is not
essential for the development of the ovum.2

In those ova which are surrounded by a membrane it is probable
that the fertilising spermatozoon bores its way through at any point
(Mammals and Amphibians). In other cases there is a small aperture
in the wall of the ovum ; this is called the micropyle (some Pisces
and Insecta). Some eggs, however, are naked, so that the sperms

1 Jenkinson, loc. cit. Further references are given in this paper.

2 For references to the original papers, which are somewhat numerous, see
Przibram, Embryogeny, English Translation, Cambridge, 1908.

FERTILISATION

183

may effect an entrance anywhere on the surface (some Echinoderms
and Ccelenterates), or there may be funnel-shaped depressions on the
egg's periphery (certain Hydromedusre).1

Tn the majority of animals only one spermatozoon normally enters
the ovum, but in some (certain insects, Elasmobranch fishes, reptiles,
earthworm, lamprey, axolotl,2 etc.), several may effect an entrance.
The latter condition is called Polyspermy. Only one sperm-nucleus
conjugates with the ovum-nucleus ; the others as a general rule
undergo degeneration, but in a few cases (Elasmobranchs and reptiles)
they are said to divide, forming accessory nuclei whose ultimate fate
is unknown.

In the hen's egg polyspermy would seem to be the normal
condition, as five to twenty-five
sperm have been observed in a
single ovum by Patterson.3 While
only one spermatozoon unites with
the egg nucleus the supernumerary
ones distribute themselves through-
out the margin of the blastodisc in
the later phases of fertilisation and
the first stages of segmentation.
They undergo a certain amount of
division, forming small groups of
daughter nuclei, and these divisions
are frequently accompanied by
slight cleavage of the surrounding
cytoplasm of the margin of the
blastodisc, forming the accessory
cleavage planes. At a later period,
when the egg has reached the
32-cell stage, they have usually
undergone degeneration and have disappeared.

In those animals in which only one sperm normally enters the
egg, pathological polyspermy may occasionally occur. In such cases
each sperm centrosome may give rise to a sperm-aster. The eggs
which are fertilised in this way either do not divide at all or go on
dividing irregularly for a short time and then perish.4

A point of considerable interest is that, in some animals, the
entry of the sperm into the egg-cell takes place very early, the
sperm remaining passive in the cytoplasm of the egg throughout

1 Wilson (E. B.), The Cell, etc., 2nd Edition, New York, 1900.

2 Jenkinson, loc. cit. Further references are given in this paper.

3 Patterson (J. T.), "Studies on the Early Development of the Hen's Egg,"
Jour. Morph., vol. xxi., 1910.

4 Wilson, loc. cit.

FIG. 58. — Fertilisation process in
bat's ovum. (After van der
Stricht.)

p.b., Polar bodies ; o.n., nucleus
of ovum ; «.«., nucleus of
spermatozoon.

1 84 THE PHYSIOLOGY OF REPRODUCTION

the growth period of the ovum in the ovary. In Histriboddh.?
Dinophilm? Sa-ccocirrus, and a number of Turbellarians, the sperms
become attached and enter the egg-cells as soon as these are
differentiated in the ovary tissue, but actually fuse with the «gg
pronuclei only when the egg has completed its full growth and
has undergone its maturation divisions. This condition has been
especially studied in Saccocirrus by Buchner.a

It is supposed that the entrance of supernumerary sperms is
prevented normally either by some mechanical means, such as the
development of a membrane formed after the penetration of the first
sperm, or else by a change in the chemical constitution of the ovum
occurring as the immediate result of fertilisation.4 Thus, the brothers
Hertwig 5 showed that in the case of eggs the vitality of which had
been reduced artificially (e.g. by poisons), the vitelline membrane
was formed so slowly after the entrance of the first spermatozoon
that others also were able to make their way into the egg cytoplasm.
On the other hand, the ova of many animals in which no membrane
is formed seem to possess the capacity of resisting the entry of
supernumerary spermatozoa, and the same is apparently the case
with those ova which have a membrane before fertilisation, this
membrane being penetrated by only a single sperm. Loeb 6 has
recently suggested that polyspermy may be prevented by an altera-
tion in the surface tension of the egg after the entrance of the
spermatozoon.

McClendon 7 and Gray 8 have shown that there is a rapid drop
in the electrical resistance of the ovum on fertilisation. Gray finds
that in artificial fertilisation brought about by treatment of the
eggs with butyric acid, this drop in resistance also takes place. A
great drop in the electrical resistance of the egg is brought about
by weak trivalent negative salt solutions, such as sodium citrate,
while trivalent salts of the positive series such as cerium chloride,

1 Shearer, " The Anatomy of Histnbodella homari," Quar. Jour. Micr. Science,
vol. lv., 1910.

2 Shearer, " The Problem of Sex Determination in Dinophilus gyrocilatus,"
Quar. Jour. Micr. Science, vol. Ivii., 1912.

3 Buchner, "Die Besamung der jugendlichen Ovocyte und die Befruchtung
bei Saccocirrus" Arch. f. Zellforsch., vol. xii., 1914.

4 Farmer, " On the Structural Constituents of the Nucleus, etc.," Croonian
Lecture, Proc. Roy. Soc., B., vol. Ixxix., 1907.

5 Hertwig (O. and R.), '' Beitrage zur Kenntniss der Bildung, Befruchtung
und Teilung des tierischen Eies," Morph. Jahr., vols. ii. and iii., 1887.

6 Loeb ( J.), The Dynamic* of Living Matter, New York, 1906.

7 McClendon, "Electrolytic Experiments showing Increase of Permeability
of the Egg to Ions at the Beginning of Development," Science, N.S., vol. xxxii.,
1910.

8 Gray (J.), "The Electrical Conductivity of Echinoderm Eggs and its
Bearing on the Problems of Fertilisation and Artificial Parthogenesis," Phil.
Trans. Roy. Soc. London, Ser. B., vol. ccvii., 1916.

FERTILISATION 185

lanthanum nitrate, cause an enormous rise in resistance, when used
in solutions of 0'0005 Molar strength. Harvey 1 has adduced a
considerable body of evidence for believing that the egg becomes
more permeable to alkalis during fertilisation. R. S. Lillie 2 has
also shown that Arbacia eggs take several times more water after
fertilisation than before.

Brachet 3 has given a very full analysis of the conditions
governing polyspermy in Amphibians. The controlling factor would
seem to be the aster and centrosome. Once the egg-aster has formed,
no extra spermatozoa can enter the egg under normal conditions, and
even in those eggs in which polyspermy has been induced by treat-
ment of the egg by chemical agents, or the use of very concentrated
sperm emulsions, it is found that one sperm never penetrates the
region of the astral rays of another sperm head. Artificial aster
formation, however, can be brought about in the ripe Echinoderm egg
by placing the egg in hypertonic sea-water. Harlent 4 has advanced
strong evidence in a recent paper to prove that this is the role of
hypertonic solutions in the various methods of producing artificial
parthenogenesis in these animals, such as those of Loeb. Loeb found
that preliminary treatment of the egg in weak solutions of a fatty
acid, such as butyric, was insufficient alone to induce development ;
subsequent treatment in hypertonic sea-water for a few minutes was
also necessary. Loeb considers that the oxidation processes set up
in the ovum by the initial treatment with butyric acid go too far
unless controlled by the second treatment. This, he believed, was
accomplished by the hypertonic sea-water. Warburg 5 and Meyerhof,6
however, have shown that a greatly increased consumption of oxygen
takes place when the eggs are placed in hypertonic sea-water. It is
probable, therefore, that hypertonic sea-water helps to initiate
parthenogenetic development on account of the aster formation it
produces in the cytoplasm of the ovum, which renders subsequent
segmentation possible. Additional evidence on this point has been
brought forward by Vies and Dragoin,7 who have shown that when
the dividing egg is subjected to increased pressure normal aster

1 Harvey (N.), "The Permeability and Cytolysis of Eggs," Science, N.S.,
vol. xxxii., 1910.

2 Lillie (E. S.), " Increase of Permeability to Water following Normal and
Artificial Activation of the Sea-Urchin Eggs," Amer. Jour, of Physiol., vol. xl.,
1916.

3 Brachet (A.), L'ceufetles Facteiirs de POntogemse, Paris, 1917.

4 Harlent, "Comment agit la solution hypertonique dans la partheno-
genese experimentalle," Arch. d. Zool. Exp,, vol. Ivii., 1918.

6 Warburg, " Uber die Oxydationen in lebenden Zellen," Arch. f. ges.
Physiol., vol. Ixvi., 1910.

8 Meyerhof, " Untersuchungen liber die Warmetonung der vitalen
Oxydationsvorgange in Eiern," Biochem. Zeitsch., vol. xxxv., 1911.

7 Vies and Dragoin, " Etudes sur la pression osmotique d'arret de la
division cellulaire," Arch. d. Biol., vol. xxxi., 1921.

1 86 THE PHYSIOLOGY OF REPRODUCTION

formation does not take place, and the chromosomes are unable to
take up their proper position in the cell for division.

In the frog it has long been known that the future axis of the
embryo is determined by the point of entry and path of penetration
of the spermatozoon, the head of the future embryo appearing
approximately opposite the point at which the sperm has entered the
ovum. Thus the future bilateral symmetry of the larva is established
in the ovum before the germ nuclei have united by the path along
which the sperm head penetrates the cytoplasm of the egg, in order-
to reach the female pronucleus.

Another change brought about in some eggs by fertilisation has
been shown by certain experiments of F. Lillie.1 He has demonstrated
that the unfertilised eggs of the Polychtet Nereis and those of the
sea-urchin Arbacia contain some substance that rapidly agglutinates
the sperm of their own species. If watery extracts are made from
the unfertilised eggs of these animals, the addition of a little of
these extracts to their sperm suspended in sea- water results in
their agglutination within a very short time, but similar extracts
of fertilised eggs are without any action when added to sperm
suspensions. He also found that extract of eggs treated with various
chemical agents such as would induce artificial parthenogenesis, was
also without any action in this respect. Bataillon2 has drawn
attention to the fact that the eggs of the frog after fertilisation are
resistant in a high degree to the cytolysing action of hepato-
pancreatic fluid. If a number of eggs of Ranafusca are inseminated,
and are then treated in this manner, it is found that about two-
thirds of their number subsequently segment in an abnormal
manner, but one-third fail to divide and swell up and are cytolysed.
It is found on investigation that these eggs are the ones that have
failed to become fertilised.

In the Mammalia fertilisation takes place usually in the upper
part of the Fallopian tube.

THE OXIDATION PROCESSES OF THE OVUM ON FERTILISATION
AND DURING EARLY DEVELOPMENT 3

Loeb was the first to advance the view that the process of the
fertilisation of the ovum was one mainly concerned with oxidations
taking place in the egg, initiated by the entrance of the sperm.
Warburg 4 was able to show that this was definitely the case. The

1 Lillie (F.), Problems of Fertilisation, Chicago University Pi-ess, 1919.

2 Bataillon, " Nouvelle contribution a 1'analyse experimentale de la feconda-
tion par la parthenogenese," Anns. Inst. Patteur, vol. xxx., 1916.

3 By C. Shearer.

4 Warburg, " Beobachtungen iiber die Oxydationsprozesse im Seeigelei,"
Zeitsch. f. Physiol. Ckem., vol. Ivii., 1908.

FERTILISATION 187

amount of oxygen taken up by the egg of the sea-urchin Arbacia
on fertilisation was quantitatively measured. The oxygen disappear-
ing from the sea-water in which the eggs had stood for some time
was determined by the Winkler method, by titration with sodium
thiosulphate. Warburg found that for a quantity of eggs that
contained 28 milligrams of nitrogen, which roughly corresponds to
about 4 million eggs, 4-5 cubic centimetres of oxygen were taken
up in the course of the first hour following fertilisation. The same
quantity of unfertilised eggs consumed 0'5-0'7 c.c. oxygen in this
time, that is, the fertilised eggs used up six to seven times more
oxygen than the unfertilised. As early cleavage and development
progressed, more and more oxygen was consumed, but in the absence
of oxygen all development was stopped. In the 32-cell stage 6'8 c.c.
oxygen were taken up, as compared with the 4 c.c. consumed in the
first hour after fertilisation. If the eggs were placed in hypertonic
sea-water the normal rate of oxidation could be increased as much
as ten times. In normal sea-water the fertilised eggs require a
constant amount of oxygen to reach a definite stage, but this stage
could be reached with half this oxygen consumption if the eggs had
been entered by more than one sperm. Since there is this great
increase in the respiratory exchange of the egg on fertilisation, and
as this always shows a certain amount of progressive increase as
development advances, it is natural to conclude that the energy
liberated in the ovum by this increased oxygen consumption is
correlated with the mitotic activity, and the various processes of
morphogenesis taking place in the fertilised egg. It is clear,
however, that this is not the case. Warburg l has shown that if
the fertilised egg is placed in strong hypertonic sea-water, or if a
little phenylurethane (aimr N) is added to the sea-water, all cell
formation is inhibited, although the egg continues to live and
undergoes a certain amount of development in the absence of cell
formation. These eggs, however, consume as much oxygen as those
in which normal cell formation and mitosis take place.

Moreover the oxygen consumption of the egg obviously fails to
keep pace with the increase in its morphological structure, for
in the sixth hour following fertilisation, although the egg is now
composed of 32 cells, the oxygen consumption has only increased
from 4-6'8 c.c. per hour. In another experiment of Warburg's a
larger number of eggs was used, 13'2 nig. of oxygen was consumed
in the 8-cell stage, while in the 32-cell stage only 20'5 nig. was
absorbed. Thus while the oxygen consumption doubled in amount,
the cell structure had increased four times. In these results we

1 Warburg, "Uber die Oxydationen in lebenden Zellen," Arch. f. ges.
Pkysiol., vol. Ixvi., 1910:

1 88 THE PHYSIOLOGY OF REPRODUCTION

also have evidence against the view that the nucleus plays the
predominant part in the oxidation processes of the cell.

It would appear from Masing's L work that there is no actual
synthesis of nucleic acid in the egg-cell during early development.
He found as much nucleic acid in the fertilised unsegmented egg as
in the 8-cell stage. In the 8-cell stage we have eight nuclei almost
the size of the nucleus of the fertilised unsegmented egg. To
account for these facts Masing suggests that in the unsegmented
egg, only a part of the nucleic acid is contained within the nucleus,
most of it being distributed throughout the cytoplasm, but as
segmentation progresses this cytoplasmic portion is gradually with-
drawn within the new nuclei.

In addition to Warburg's work, Meyerhof 2 has also carried out
a series of extensive researches on the energy changes taking place
within the egg of the sea-urchin Stronglocentrotus during fertilisation
and early development. The heat production of the egg was
measured. and correlated with the amount of oxygen consumed.
The heat liberated by the eggs was determined by means of a finely
divided Beckmann thermometer, the eggs being contained within
a small vacuum flask, sunk in the water of a carefully regulated
thermostat tank. The oxygen consumption was estimated by the
Winkler method.

Meyerhof found the heat production of a quantity of unfertilised
eggs, containing 140 mg. of nitrogen (about 17 million eggs), to be
about 0'9 gram-calorie per hour, while the same quantity of fertilised
eggs liberated 4-4'2 gram-calories in this time. In the second hour,
the 2-cell stage, the heat production rose to 4*5-5 gram-calories.
In the fourth hour, corresponding to the 8-cell stage, it was
6-6*5 gram-calories. In the sixth hour, the 32-cell stage, it was
9*8 gram-calories, and from this stage onwards the heat liberation
increased rapidly, until in the eighteenth hour, when the free
swimming stage was reached, it was 17'8 gram-calories per hour,
or four times the amount in the first hour following fertilisation.

The heat given off by a known quantity of eggs, expressed in
gram-calories per hour, divided by the quantity of oxygen consumed
in the same time, expressed in milligrams, gave Meyerhof a calorific
quotient. He found this quotient for the early stages of develop-
ment to average 2-75, but if the heat of solution of carbon dioxide
and its combination to form sodium bicarbonate in sea-water is
taken into consideration, this value is reduced to 2'6. This figure
is remarkably low, for Ziinst and Schumburg, Eauber, Pfliiger and

1 Masing, " Uber das Verhalten der Nucleinsiiure bei der Furchung des
Seeigeleis," Zeitsch. f. Physiol. Chem., vol. Ixvii., 1910.

2 Meyerhof, " Untersuchungen iiber die Warmetonung der vitalen
Oxydationsvorgange in Eiern," I., II., III., Biochem. Zeit., vol. xxxv., 1911.

FERTILISATION 189

others, have shown that when fat is burnt this figure should be
in the vicinity of 3'3, when protein 3'2, and for carbohydrate 2'9.
Meyerhof could find no carbohydrate in the egg, and there was no
destruction of protein, but sufficient fat was found in the eggs to
give the quotient observed.

The most important fact arising from Meyerhofs experiments
was that whether he took the unfertilised egg, the fertilised, or
the fertilised >egg treated with phenylurethane, in which cell
division had been inhibited, the value of his calorific quotient was
always the same. If any of the chemical energy liberated in
the egg, as the result of the oxygen consumption, was utilised in
any of the processes of morphogenesis, these values could not
be the same in every instance. In the case of fresh sperm, the
calorific quotient was 3-1, or something approaching normal. The
evidence both of the oxygen consumption and the heat liberation
of the developing egg, then, seems to show there is little direct
connection between the oxidations taking place, and the appearance
of visible morphological structure, and this is borne out by the
calorific quotient, which is the same for the fertilised segmenting
and the unfertilised egg.

If the energy of the egg is not employed in this manner how is it
utilised? Warburg1 suggests that it is used in performing work
which is indispensable to the life of the cell. Thus it might be used
in keeping certain constituents of the cytoplasm apart, holding the
cell-membrane intact and semipermeable, in which respect the
electric charge on the surface plays so important a part as
the experiments of Girard2 show. That the cytoplasm of egg-
cell in the living state is sharply divided into a number of
regions, in which different reactions are taking place, has been
clearly demonstrated by the microdissection methods of Chambers,3
Kite,4 Barber,5 and Seifriz.6 These, then, are a few of the ways
in which this energy of the cell might be utilised.

It has been long recognised by morphologists that cellular
structure is no criterion of organisation, for many of the Protozoa

1 Warburg, "Beitrage zur Physiologic der Zellen," Ergebnisse der Physi-
ologic, vol. xiv., 1914.

2 Girard, "Scheme physique pour servir a 1'etude de la nutrition minerale
de la cellule," Compt. Rend. Acad. de Science Paris, vol. clxviii., 1919.

3 Chambers (E.), " Microdissection Studies," I. and II., Amer. Jour, of Physiol.,
vol. xliii., 1917, and Jour, of Exp. Zool., vol. xxiii., 1917.

4 Kite, "Studies on the Physical Properties of Protoplasm," Amer. Jour.
of Physiol., vol. xxxii., 1913.

5 Barber, "The Pipette Method in the Isolation of Single Micro-
organisms and in the Inoculation of Substances into the Living Cells," Phillip.
Jour. Science, vol. ix., 1914.

0 Seifriz, "Viscosity Values of Protoplasm as Determined by Micro-
dissection," Bot. Oaz., vol. Ixx., 1920.

190 THE PHYSIOLOGY OF REPRODUCTION

possess an organisation more complex than many of the simpler
Metazoa. Moreover, many animal eggs, such as those of the
Cephalopod Loligo, and many Arthropod eggs, begin to assume the
shape of the future larval form through which they will subsequently
pass in their ontogenetic history before any cleavage has taken place,
clearly showing preformation in this respect.

In many eggs, again, the entrance of the sperm is followed
by rapid changes in the viscosity of the cytoplasm, followed by
streaming effects within the egg. In the Ascidian Cynthia, Conklin l
has shown that the cytoplasm of the ripe egg consists of a grey yolky
substance occupying the centre of the egg, and surrounded by a
peripheral layer of bright yellow pigmented cytoplasm, while at the
animal pole is an area of clear cytoplasm, the germinal vesicle. On
the entrance of the spermatozoon, an immediate rearrangement of
these materials takes place. The yellow cytoplasm now streams
down to the negative pole of the egg and arranges itself symmetri-
cally with regard to the egg axis, while the clear cytoplasm of the
germinal vesicle comes to lie above it. The grey yolk now lies
at the animal pole containing the female pronucleus embedded
in it.

That the entrance of the sperm into the egg of the sea-urchin
initiates some structural mechanism in the egg, by virtue of which
its high rate of oxidation in the fertilised condition -is rendered
possible, would seem to be borne out by experiments of Warburg
and Meyerhof.2 They found that, if they ground up the eggs
with sand and sea-water to a tine paste, the unfertilised eggs
consumed just as much oxygen in the broken condition as when
intact and whole. There was only a slight and very insignificant
fall in the respiratory quotient. If the fertilised eggs were reduced
to a paste, then, instead of this having the normal respiratory
quotient characteristic of the fertilised egg, it was invariably a third
or fourth of this amount. Thus the rubbing up with sand made
little difference in the case of the unfertilised egg, but was followed
in the fertilised egg by an enormous drop in the respiratory quotient.
That this mechanism is not bound up in any way with the usual
visible structure of the egg is shown by further experiments, in
which the eggs were treated with acetone. It was found that
acetone is an excellent fixative for the egg, preserving the minute
details of microscopical structure and chemical composition
unchanged ; even the egg lipoids seemed unaffected by the use of
acetone. In the case of the unfertilised egg, not a great deal of

1 Conklin, "The Organisation and Cell Lineage of the Ascidian Egg,"
Jour. Acad. Nat. Science Phild., vol. xiii., 1905.

2 Warburg and Meyerhof, "Uber Atmung in abgetoteten Zellen und
Zellenf ragmen ten," Arck.f. ges. P/tysiol., vol. cxlviii., 1912.

FERTILISATION 191

difference between the eggs treated with acetone and the untreated
could be observed ; both consumed almost the same quantity of
oxygen. In the case of the fertilised eggs there was again, as with
the eggs rubbed with sand, an enormous drop in the respiration.
The eggs after treatment with acetone can even be dried, when they
can be reduced to a very fine powder. This powder, when dissolved
in water, still shows considerable respiratory power. The unfertilised
acetone egg powder, however, shows almost as much consumption of
oxygen as the intact egg, while the fertilised acetone egg powder
shows a drop of over 90 per cent, in its power of consuming oxygen.
None of these egg powders give off C02.

In the more recent work on the oxygen consumption of the egg,
the Winkler titration method has been superseded by the more
accurate and convenient Barcroft differential manometer method.
The advantage gained by the use of the manometer is that continuous
observations can be made on the same material, and the respiratory
exchange can thus be followed minute by minute.

Warburg1 (1915), using this instrument, has made a rein-
vestigation of the respiratory exchange of the egg of Stronglocentrotus
during the first twenty-four hours of development. He found that a
quantity of unfertilised eggs that contained 20 mg. of nitrogen, at a
temperature of 23° C. consumed 10-14 cubic millimetres of oxygen
in twenty minutes. The fertilised egg, ten minutes after the addition
of the sperm, consumed 60-84 cub. mm. under the same conditions.
That is, ten minutes after fertilisation the oxygen consumption of the
egg was 6 times greater than before fertilisation. In the sixth
hour the oxygen consumption was 12 times that of the unfertilised
egg, at twelve hours 16 times; while at twenty-four hours it was
22 times the amount of the unfertilised egg. As Warburg states,
it is highly remarkable that in one and the same cell substance,
which receives no addition of fresh material from any external
source, we should find, as the result of fertilisation, in the course of
twenty-four hours a rise in its oxidation rate equivalent to some-
thing like 2,000 per cent.

On the whole the manometer seemed to show that there was a
much closer agreement between the increase in the respiratory
quotient and the growth of visible structure of the egg. In all
instances the CO2 output of the eggs follows the oxygen consumption
very closely, the respiratory quotient being about 0'9. The respira-
tion of a single spermatozoon was found to be 1,500-2,000 times
smaller than the egg.

In the past season the investigation of the problem has been

1 Warburg, "Notizen zu Entwicklungsphysiologie des Seeigeleies," Arch,
f. ges. Physio!., vol. clx., 1915. > ,

192

THE PHYSIOLOGY OF REPRODUCTION

carried a step farther l by the employment of a special type of the

manometer, in which it was pos-
sible to bring about the fertilisa-
tion of the eggs within the closed
chambers of the apparatus. It
was then possible to observe the
respiration of the egg at the actual
moment of entry of the sperm.
The eggs and sperm of Echinus
microtuberculatus were used. On
the addition of the sperm to the
eggs there is always an immediate
and almost instantaneous con-
sumption of oxygen by the eggs.
In the course of the first minute
the uptake of oxygen is many
times that of the same eggs one
minute before the addition of the
sperm, and more is usually taken
up in the first minute than is
taken up in the second, third, and
fourth minutes, after the addition
of the sperm, taken altogether.

In all instances the C02 out-
put of the eggs follows the oxygen
uptake very closely, the respiratory
quotient being in the neighbour-
hood of 0-92.

At standard barometric pres-
sure, and temperature of 14'5° C.,
it was found that 4'06 mg. of egg
nitrogen (£ million eggs) before
fertilisation consumed T5 cub. mrn.
of oxygen in ten minutes; after
fertilisation the same eggs con-
sumed 56 cub. mm. in this time ;
there was thus an increase in the
respiratory quotient of the eggs ten
minutes after fertilisation of some-
thing like thirty-seven times that
of the unfertilised condition. If
we consider the increase taking

5
Minutes .

FIG. 59. — Chart showing the amount
of oxygen taken up, and the carbon
dioxide given off, in the first ten
minutes after the addition of the
sperm to the eggs of Echinus mic-
rotuberculatus , 56 cub. mm. of
oxygen being taken up by the
fertilised egg in this time, as com-
pared with 1'5 cub. mm. oxygen
consumed by the same eggs in the
unfertilised condition in the same
interval.

Unbroken curve = oxygen ; broken
curve = carbon dioxide.

Respiratory quotient, about 0*9.
Half a million eggs (4'06 mg. egg
nitrogen). Temp., 14'5° C. Bar.
760 mm. Hg.

1 Shearer, "On the Oxidation Processes of the Echinoderm Egg during
Fertilisation," Proc. Roy. Soc. London, B., vol. xciii., 1922.

FERTILISATION

193

place at the end of the first minute after the addition of the sperm to
the eggs, we get even more striking figures. The oxygen consumption

FIG. 60. — The insemination of the eggs of Saccocirrus while these are under-
going growth in the ovarian tissue. The long black rod -like body in the
cytoplasm of the primitive ovocytes is the spermatozoon. It will be
seen that the ovum develops from a very early stage with the spermatozoon
in its cytoplasm, actual fusion of sperm and female pronucleus only taking
place after the eggs are laid and have undergone meiosis. (From Buchner's
Praktikum far Zrtlenlehre, Bd. i., Borntraeger.)

of the unfertilised egg is so low, however, that its measurement for
so short a time is difficult with the quantity of eggs usually employed
(£ to 1 million eggs) in an experiment, as usually no reading can

7

194 THE PHYSIOLOGY OF REPRODUCTION

be observed on the manometer scale. If we take the reading on
the unfertilised eggs at the end of ten minutes, we can probably
approximate to it roughly by dividing this figure by 10. It works
out for a number of experiments at something like 0'15 cub. mm.
of oxygen per minute. The same eggs fertilised consume in the
first minute after the addition of the sperm 12 cub. mm. of oxygen.
Thus the addition of the sperm to the eggs causes, within the space
of ore minute, an increase in their oxygen consumption of something
like eighty times that observed on the same lot of eggs one minute
previous to the addition of the sperm.

The examination of sections of fixed material of these fertilised
eggs shows that the process is by no means an instantaneous one,
and that the sperm take ten to fifteen minutes before they find
their way into the actual cytoplasm of the eggs.

This initial oxygen consumption of the egg immediately on
fertilisation must be induced by the first contact of the sperm
with the external surface of the egg-membrane. We arrive then
at the remarkable conclusion that mere contact of the spermatozoon
with the external surface of the egg-membrane is capable of
increasing the oxygen consumption of the egg by something like
8,000 per cent, in the course of one minute.

There are good reasons for believing, as the result of Loeb's
experiments on the fertilisation of the eggs of Stronglocenirotus with
the sperm of Astcrias, and. Lillie's description of the process of
fertilisation in Nereis, that the entry of the spermatozoon into the
egg consists of two distinct phases. First, an external one, in which
certain changes are brought about in the cortical substance of the egg
the moment the sperm make contact with the external surface of the
egg -membrane. This would seem to be correlated with this initial
oxidation taking place in the egg as described above for E. micro-
tuberculatus. Secondly, the changes following the actual entry of the
spermatozoon into the egg cytoplasm itself, which, as Lillie has shown
in Nereis, only takes place some thirty minutes after the first phase
of fertilisation, and in the sea-urchin, follows some ten to fifteen
minutes after the sperm are added to the eggs.

By centrifuging the eggs of Nereis before the sperm has actually
penetrated the egg-membrane, Lillie was able to separate the jelly
surrounding the egg and containing the spermatozoon from the egg
itself. These eggs complete meiosis which has been initiated by the
spermatozoon, but never segment. A typical segmentation nucleus
is, however, formed, which breaks down, leaving the chromosomes
free in the egg cytoplasm ; they split longitudinally in the normal
manner but never separate. No asters or mitotic spindles appear in
these eggs, as when the complete process of fertilisation is allowed to

195

take place, and in the absence of these structures the process of cell
division makes no further progress, and the chromosomes finally
degenerate and break down. This experiment clearly proves that
the sperm bring about profound alterations in the egg while still
external to the egg-membrane. Loeb has shown that when the eggs
of Stronglocentrotus are fertilised with the sperm of Asterias, in
hyper-alkaline sea-water, they only form fertilisation membranes ; no

J>

FIG. 61. — The entrance of the spermatozoon into the egg of Nereis.

Penetration of the spermatozoon in the egg of Nereis, from sections : a, thirty-
seven minutes after insemination ; b, c, </,. three stages from eggs killed
forty-eight and a half minutes after insemination ; e, fifty-four minutes
after insemination ; the head of the spermatozoon now entirely within the
egg is contracting while the middle-piece of the spermatozoon remains on
the egg-membrane ; it never enters the egg ; the tail also remains outside.
(From Lillie's Problems of fertilisation, University of Chicago Press.)

actual segmentation takes place unless the eggs receive further
treatment so that artificial parthenogenesis is induced (see p. 236).

Meyerhof and Warburg in many of their experiments have shown
that any injury or cytolysis of the egg-membrane is invariably
followed by a great increase in the oxygen consumption of these eggs.
Meyerhof1 found that this is usually accompanied by an increased
liberation of heat. In eggs treated with weak solutions of NaCl in
which the normal condition of the cell wall is destroyed in the
absence of Ca and K ions, the rise of oxygen consumption was five

1 Meyerhof, " Die Atmung der Seeigeleier (S. lividus) in reinen Chlornatrium-
losungen," Biochem. Zeit., vol. xxxiii., 1911.

196 THE PHYSIOLOGY OF REPRODUCTION

times that of the same quantity of untreated eggs. The heat
production was increased from 0'9 gram-calorie per hour to 3'4 gram-
calories per hour, after treatment with valerianic acid by which
artificial membrane formation was induced.

A great many of Loeb's and Warburg's experiments point con-
clusively to the cortical layer of the egg and the egg-membrane as
being the controlling factors in the oxidation processes of the egg.
Any change brought about in these is immediately reflected in the
oxygen uptake of the egg. Loeb has, of course, based his method of
producing artificial parthenogenesis on the fact that alteration of the
surface layer of the egg renders the commencement of development
possible. But how can the cytolytic destruction of the surface layer
of the egg lead to development ? Warburg has shown that there
are good reasons for believing that the oxidations taking place
in the egg occur mainly at its surface, for NaOH, which does
not diffuse into the egg, raises the rate of oxidations more than
NH4OH, which readily diffuses into the egg.

Moreover, he found1 that the addition of iron salts to the broken-
up eggs, or acetone egg powder, was followed by a considerable increase
in the oxygen consumption of these egg preparations, and he found
marked traces of iron in the sea-urchin egg. He suggests that the
iron probably acts the part of a catalyser. If the iron were located
in the lipoid layer of the egg in a condition in which it was unable to
act, some slight alteration in this layer, due to the action of the
sperm, might render it active or bring both the iron and the oxidisable
substrate into a condition in which they could quickly interact. We
know from Thunberg's work2 that lecithin in a watery suspension
consumes considerable oxygen in the presence of iron salts. The egg
of the sea-urchin contains considerable quantities of this lipoid.

Warburg has pointed out that there are many respects in which
the metabolism of the fertilised egg resembles that of the yeast-cell.
In each it has been shown that structure plays a very important
part, as both acetone preparations of the egg and the yeast-cell
retain considerable respiratory power. Meyerhof3 finds, however,
that if acetone yeast is well washed with water, it soon loses its
capacity to take up oxygen. If a little watery extract of yeast is
added to the washed yeast it immediately regains its lost respiratory
power. In the water used in washing the yeast Meyerhof found the

1 Warburg, " Uber die Rolle des Eisens in der Atmung des Seeigeleis-
nebst Bemerkungen iiber einige durch Eisen beschleunigten Oxydationen,"
Zeitsch. P/iysiol. Ckem., vol. xcii., 1914.

2 Thunberg, " Untersuchungen iiber autoxydable Substanzen und autoxy-
dable Syateme von physiologischen Interesse," Skand. Arch. Physiol., vol.
xxiv., 1911.

3 Meyerhof, "Untersuchungen zur Atmung getoteter Zellen," Archiv. f.
ges. Physiol., vol. clxx., 1918.

FERTILISATION 197

presence of some compound containing the (SH) group. Hopkins

has recently isolated from the yeast-cell a substance which is

undoubtedly closely related, if not identical with this respiratory

body of Meyerhof. It proves to be a combination of two amino-

acids, glutamic acid and cystine, to which Hopkins1 has given the

name of Glutathione. This dipeptide possesses most remarkable

properties in that, in the reduced (SH) form, it can take up

molecular oxygen, while in the oxidised (S-S) form so produced it

can act as a hydrogen acceptor, and can catalyse oxidations of the

Wieland type, in which no activation of oxygen probably takes place,

but an activation of hydrogen occurs instead. In the presence of a

suitable acceptor the hydrogen is removed and the oxidation of the

original substance takes place. It can therefore be both reduced

and oxidised under the influence of factors known to be present

in the tissues themselves. Moreover, it possesses precisely those

properties which a co-ferment adapted to an oxidase system would

possess, and at present stands entirely in a class by itself. Hopkins

has shown that it is present in most living cells, but he could find

no trace of it in the hen's egg, although it was very obviously

present in the thirty-hour chick embryo. I find, however, that in

the ripe eggs and sperm of the sea-urchin Echinus miliaris, it is

invariably present in very appreciable quantity, but one minute

after fertilisation the same eggs give a very pronounced magenta

colour by the nitro-prusside test. It; is very readily washed out of

the eggs by heating them in sea-water in the presence of a little

acetic acid ; when its presence can be shown in the water, the washed

eggs then no longer give the test. In the unripe egg, in which the

egg nucleus is plainly visible, in a number of instances I could find

no trace of its presence. In the ripe eggs it is present in very

variable quantities, the eggs of no two females giving the same result,

probably depending on varying degrees of ripeness of their gonads.

In several samples of ripe sperm it was present in much greater

quantity than in any of the eggs examined. There are many

points of interest brought up by the presence of this remarkable

substance in the fertilised egg, and there is every reason to believe

its study in the future will reveal many interesting facts with regard

to the respiratory exchange in the egg on fertilisation.2

THE HEREDITARY EFFECTS OF FERTILISATION

The attempts that have been made to interpret the nature and
essence of sexual reproduction may be ranged under two heads,

1 Hopkins, " On an Autoxidisable Constituent of the Cell," Biockem. Jour.,
vol. xv., 1921.

2 Shearer, "On the Oxidation Processes of the Echinoderm Egg during
Fertilisation," Proc. Roy. Soc. London, B., vol. xciii., 1922.

198 THE PHYSIOLOGY OF REPRODUCTION

representing the two chief theories that have been elaborated (with
some modifications by their respective adherents) to explain the
observed phenomena.1 According to one hypothesis, conjugation
of the gametes results in a rejuvenescence which is essential for the
perpetuation of the race (see p. 221). According to the second
theory, which is not necessarily antagonistic to the first, gametic
union is a source of variation.'2 The latter theory may now be
briefly considered. A full discussion of the hereditary effects of
fertilisation is, however, beyond the scope of the present work.

The doctrine that conjugation is a source of variation was first
promulgated at the beginning of the last century by Treviranus.
Subsequently Brooks 3 adopted the same idea, and Weismann made
it the basis of his famous theory of heredity.4 " Sexual reproduction
is well known to consist in the fusion of two contrasted reproductive
cells, or perhaps even in the fusion of their nuclei alone. These
reproductive cells contain the germinal material or germ-plasm, and
this again, in its specific molecular structure, is the bearer of the
hereditary tendencies of the organisms from which the reproduc-
tive cells originate. Thus, in sexual reproduction, two hereditary
tendencies are in a sense intermingled. In this mingling I see the
cause of the hereditary individual characteristics; and in the pro-
duction of these characters the task of sexual reproduction. It has
to supply the material for the individual differences from which
selection produces new species."

Weismann supposes the nuclear chromatin of the cell to consist
of a large number of self-propagating vital units which he calls
biophors. These biophors he believes to be grouped together to
form more complex units, named determinants, which represent the
separate parts of the organism. The determinants are supposed to

1 For accounts of the various theories which have been put forward con-
cerning the nature of fertilisation, see Wilson, loc. cit., Geddes and Thomson,
The Evolution of Sex, 2nd Edition, London, 1901 ; Weismann, The Evolution
Theory, English Translation, London, 1904 ; and Lock, Variation, etc., London,
1908. Further references are given in these works.

2 A third theory, which has never obtained any great support among
biologists, suggests that the purpose of sexual reproduction may be to prevent
variation, and so preserve specific uniformity. According to this view the
sexual process, although continually creating new variations, is also constantly
obliterating them by tending to produce individuals possessing the mean of
their parents' characters. This theory, which is the converse of the second
theory referred to in the text, has received the support of the Hertwigs. In
this connection it may be remarked that variability is quite as great among
non-sexual parthenogenetic animals as among those which are reproduced
sexually. This fact is difficult to explain if we adopt the theory that the
purpose of gametic union is to induce variability. Moreover, Enriques ("La
Coniugazione e il differenziamento sessuale negli Infusori," Arch. f. Protiati'it-
kunde, vol. ix., 1907), as a result of a series of experiments upon conjugation
in Infusoria, has adopted a similar view to that of the Hertwigs.

3 Brooks, The Law of Heredity, Baltimore, 1 883.

4 Weismann, The Germ- Plasm, English Translation, London, 1893.

FERTILISATION 199

be aggregated together to comprise units of a still higher order,
known as ids. These are identified with the chromatin granules.
Every part of the organism (or every character that it possesses) is
believed to be represented in an id. Moreover, Weismann assumes
that the ids vary slightly in related individuals, the differences in
the ids corresponding with the variations in the species. Lastly, the
ids are said to be arrayed in linear series so as to form idants.
Weismann identifies these with the chromosomes. It follows,
therefore, that each chromosome represents a particular group of
slightly differing germ-plasms. The purpose of variation, as
expressed in the terms of this theory, is to produce new combina-
tions of heritable variations by the mixture of different ids. And
since the number of chromosomes, and consequently the number of
ids, is doubled as a result of the conjugating process, the complexity
of the chromatin would become indefinitely increased if there were
no periodic reduction. But this, according to Weismann, is provided
against in the maturation process of the gametes, when the quantity
of chromatin in the cells becomes reduced by one-half, as described
in the preceding chapters.

The reduced number of chromosomes is supposed to contain all
the primary constituents of each of the two parents. And what is
more, according to this theory, every gamete contains ids which are
derived, not only from both the parents, but also from the ancestors,
all the immediate ancestors being represented.

Weismann's theory of the nature of fertilisation was accepted by
many biologists as a working hypothesis until the disinterment of
Mendel's discovery about twenty years ago. The confirmation of this
discovery by numerous workers in different fields has led to a
revision of many of Weismann's conceptions.

The original experiments of Mendel l were upon hybridisation
in peas, the two parent varieties initially selected differing from each
other in one particular character. The hybrids produced by crossing
were all similar superficially, and resembled one of the parents in
the character in question, which was therefore called the dominant
character, the other character being known as recessive. When the
hybrids w.ere crossed among themselves, approximately one-half of

1 Mendel, "Versuche iiber Pflanzen Hybriden," Verh. natur. f. Ver., in
Briinn, vol. iv., 1865. Reprinted in English in Mendel's Principles of Heredity
(Batesoii), Cambridge, 1902. Mendel's work was rediscovered and confirmed
by de Vries, Correns, and Tchermak in 1900, and subsequently by Bateson
and a large number of other workers. For a general account of the Mendelian
theory, and numerous references to the literature of the subject, see Bateson,
loc. cit. ; also Bateson, Saunders, Punnett, and Hurst, etc., in Reports to the
Evolution Committee of the Royal Society, Parts I., II., III., IV., and V.,
1902, 1905, 1906, and 1909; Punnett, Mendelisrn, 5th Edition, London,
1919 ; and Morgan, The Physical Basis of Heredity, Philadelphia and London,
1920.

200 THE PHYSIOLOGY OF REPRODUCTION

the offspring were found to be identical with their hybrid parents
(dominant hybrids), one-quarter resembled one of the original
varieties (the grandparent with the dominant character), while the
remaining quarter were like the other pure variety (the grandparent
with the recessive character). Consequently the pure dominants
and the dominant hybrids resembled one another outwardly, but
they differed in their capacity to transmit the characteristics in
question, since the pure dominants alone were capable of always
breeding true. The recessives also invariably bred true. Mendel
drew the conclusion that in the hybrid the gametes (both male and
female) were of two kinds, which were respectively identical with
the two kinds represented by the gametes of the original pure
varieties. The differentiation of gametes carrying different
characters is the essential principle in Mendel's theory, the existence
of dominant and recessive characters, though often observable, being
by no means universal.

Another example, taken from the work of Bateson and Punnett,
will be sufficient to elucidate further the Mendelian conception of
gametic differentiation. Breeders of blue Andalusian fowls have
always recognised the practical impossibility of obtaining a pure
strain of this breed. However carefully the birds are selected they
invariably produce two sorts of " wasters," some being pure black,
and some white with irregular black marks or splashes. Bateson
and Punnett were the first to supply the explanation. They found
that, on breeding from a large number of blue Andalusian fowls, on
an average half of the offspring were blue like the parents, a quarter
were black, and a quarter were " splashed- white." They conse-
quently drew the conclusion that the mechanism of inheritance in
the Andalusian fowl is comparable to what Mendel supposed to exist
in his hybrid peas. The gametes of the breed, according to this
hypothesis, instead of being all similar and carrying the blue
character (as one would suppose on Weismann's theory), are of two
different kinds, those of the one kind being bearers of the black
character, and those of the other being bearers of the splashed-white
character. Such gametes, uniting by chance when the fowls mate
together, give rise to three kinds of offspring, one black-white
(becoming blue, actually, like the parents), one black-black, and one
white- white, these appearing (on an average) in the proportion of
2:1:1 according to the law of probability. In this particular case
of Mendelian inheritance, neither of the two alternative parent
characters (i.e. neither black nor splashed-white) is dominant and
neither is recessive. Why black-bearing gametes uniting with
white-bearing gametes should give rise to blue individuals the
Mendelian theory does not attempt to explain.

FERTILISATION 201

The importance of Mendel's discovery lies in the fact that it
forms the basis of a theory whereby variability can be discussed in
terms of the conjugating cells themselves, and not merely in terms of
the resulting zygotes. Moreover, it is a theory which has been found
to be applicable to a very wide class of facts ; and it differs from
other theories of heredity in that it stands the test of a true scientific
hypothesis in enabling one to predict phenomena which on no other
theory could be predicted.1 There are reasons for supposing that sex
may be a Mendelian phenomenon ; that is to say, that the ova and
spermatozoa are themselves sexual entities prior to conjugation (see
p. 671). It still remains to be proved, however, that the principles
underlying Mendel's theory are applicable to all forms of inheritance.2

It has been mentioned that on Weismann's hypothesis every
gamete contains ids representing both its parents and all its
immediate ancestors. On the other hand, according to the Mendelian
theory, although all the essential characters of the organism are
represented in each germ-cell, the Mendelian characters, or allelo-
morphs as they are called, are each represented by paternal or
maternal ids only, and not by both, while the immediate ancestors
have no representation at all. It has been supposed that the
chromatin granules (which Weismann identified with the ids) are
the carriers of the Mendelian allelomorphs, and that when these
fuse together during the conjugation of the chromosomes which
precedes the process of reduction (see p. 125), there is an exchange
of allelomorphs between the chromosomes.3 If this interpretation
is correct, it is simply a matter of chance whether an allelomorph
remains in the chromosome which originally contained it, or becomes
transferred to the other chromosome of the conjugating pair. And
since each of the two chromosomes passes into a different product of
cell division, the allelomorphs would become distributed in precisely
the kind of way that the Mendelian theory postulates.4

The Mendelian investigators have shown that by experimental
breeding it is apparently possible to superimpose certain characters
belonging originally to one kind of individual, upon different
characters belonging to another kind, thus creating new combina-
tions of characters. Thus it is claimed that by starting with two
individuals, each possessing two unit or allelomorphic characters,
which we may call A and X (associated together in one individual)
and B and Y (associated in the other), it is possible in two genera-

1 Marshall, "The Categories of Biological Science," Mind, vol. xxix., (Jan.)
1920.

2 Cf. Darbishire, "Recent Advances in Animal Breeding," Royal Horti-
cidtural Society's Report of the Conference on Genetics, London, 1907-

3 For the evidence see Morgan, loc. cit.

4 Lock, loc. cit.

202 THE PHYSIOLOGY OF REPRODUCTION

tions to produce new individuals in which the combinations are
interchanged, A being associated with Y, and I> with X.1 It has
been claimed also, that, in spite of the new combinations, each of
the original separate unit characters can be preserved in a state
of complete purity, and without in any way affecting, or being
affected by, the characters upon which they have been superimposed.
By resorting to such methods, it has been thought possible to build
up, little by little, entirely fresh types of organisms, possessing new
combinations of pure characters, which previously existed only in
different individuals.

It remains to be considered how far this conception of an
organism as an individual capable of description in terms of unit
characters (each of which can be transmitted pure) is in harmony
with modern physiological theory, or justified by experimental
investigation.

In the first place, it may be pointed out that the entire trend of
physiological research in recent years has been to show that the
correlation that exists even between remote parts of the body is
often extraordinarily close, and that in all probability there is not
an organ or structure that is not dependent in its growth and
activity upon chemical substances, elaborated by other and some-
times distant parts of the body, and carried thence in the circulating
blood. Thus a change in the whole metabolism, producing palpable
modification in whole groups of characters, may be induced experi-
mentally in the individual, by interfering with or removing one
particular organ. This is well shown in the various kinds of
correlation existing between the organs of internal secretion. Again,
a change in the environment may directly affect the metabolism,
and so influence all the characters of the body. To the physiologist,
therefore, a so-called unit character cannot readily be regarded
as something represented by a substance located originally in a
chromosome or chromomere. Such a view, as Yerworn - remarks,
is " too morphologically conceived." It is more in keeping with
the physiological view of life to regard the characters of the
individual as manifestations of a particular kind of metabolism,
which is itself partly the outcome of environmental influences, and
partly the developmental result of the sort of metabolism that
existed in the germ-cells from which the organism was derived.
According to this view, it is clear that the presence of any one
characteristic may exert an influence upon many, if not upon all,
the other characteristics, and that, even in heredity, one cannot hope

1 The first filial generation is spoken of as wie Fj generation, the second filial
generation as the F2, and so on.

2 Verworn, he. cit.

FERTILISATION 203

to alter any single organ or structure without affecting, in some
slight degree at any rate, all, or nearly all, the other parts of the
body. It may be argued, therefore, in criticism of the Mendelian
conception of unit characters, that it takes little or no account of
the metabolism of the organism as a whole. Thus it has been shown
that in the case of presence or absence of hair pigment (which has
been regarded as a simple example of alternate characters, such
as can be superimposed experimentally upon other characters in
the course of two generations), there is a pronounced correlation
between albinism and other characteristics of the body, these
characteristics depending for their existence upon a common
metabolism. Moreover, the difficulty experienced by Wood l in
superimposing the complete hornlessness of Suffolk sheep upon
the white face of the Dorset horns, is probably another example
of the physiological correlation subsisting between different, and
apparently unconnected, structures. Originally, this case was
regarded as one of simple superposition, and Bateson2 describes
the hornless character as having been transmitted "pure," but
subsequently many of the so-called hornless sheep were found to
have grown scurs. The explanation which I tentatively suggest is,
that the character of pure hornlessness was somehow or other
incompatible with the pure white-faced character, these two
characters being ordinarily indications of two sorts of metabolism,
in just the same kind of way as the beef-producing quality and
the milk-producing quality seem to be to some extent incompatible
in cattle. I am inclined to go further, and to suspect that many
of the other Mendelian cases, when examined more critically, will
show that no one character can be superimposed upon another, in
experimental breeding, without altering, though perhaps only very
slightly, the character upon which it has been superimposed.

Experiments in which Merino rams were crossed with Shrop-
shire ewes3 have shown that the more important characteristics
of the body or carcass (that is to say, the " mutton points " ) may
be transmitted to the third generation so as to reappear in new
combinations in the cross-bred sheep. Thus taking the four points,
" over the shoulder," " behind the shoulder," " top of leg," and " loin,"
which are widely different in Merinos and Shropshires (being

1 Wood (T. B.), " The Inheritance of Horns and Face-Colour in Sheep," Jour.
Agric. Science, vol. iii., 1909.

2 Bateson, Mendel's Principles of Heredity, Cambridge, 1909. No doubt,
however, it is arguable that the scurs themselves represent unit characters, and
that if the scurs are of different kinds, these also represent unit characters
(which have hitherto somehow remained " latent "), and that if they occur with
different degrees of development, these again are unit characters. And so on.

3 Mackenzie and Marshall, " The Inheritance of Mutton Points in SLeep,"
Trans. Highland and Agric. Soc., 1917.

204 THE PHYSIOLOGY OF REPRODUCTION

" bad " in the former and " good " in the latter in regard to mutton
production), segregation appeared very clearly in animals of both
the second and third generations, the points being reproduced in all
possible combinations among the cross-bred sheep. This case of
Mendelian transmission is all the more remarkable in that the
characters are not superficial but deep-seated and relating to bodily
conformation, each of them depending on a number of anatomical
factors. It cannot be said, however, that all the characters were
inherited " pure " or without being influenced by the other charac-
ters with which they entered into new combinations, and in some
cases the points shown were definitely composite, being dissimilar
to those of both the parent breeds.

When, as a consequence of cross-breeding two varieties, the
alteration of the parent characteristics is minimal the transmission
of pure characters — according to Mendelian expectation — may be
said to occur, and experimental evidence has shown that there are
considerable numbers of such cases. It is a legitimate field of
work for the biometrical school of biology to determine by
statistical methods the extent to which variation occurs as a
result of attempted superposition of characters which in their
" pure " state are physiologically incompatible. Furthermore, a
latent character may be regarded as one, the outward manifesta-
tion of which is incompatible with the existing kind of metabolism,
but which is capable of reappearance as soon as the conditions
become favourable. But because it is helpful to assume that latent
characters are present in some manner in the animal organisation, it
is not necessary to assume that they are definitely located in the nuclei
of germ-cells or in any other particular structures l (see pp. 674-675).

Moreover, it should be remembered that there is no experimental
proof that the chromosomes of the gametes constitute the entire
physical basis of inheritance. The best evidence in support of this
supposition appears to be Boveri's experiment, in which he fertilised
a non-nucleated ovum of one species of sea-urchin with the sper-
matozoon of another species.2 The resulting pluteus or larva was
purely paternal in its characters. Boveri concluded, therefore, that
this result was due to the introduced nucleus, the maternal cytoplasm
having no determining effect upon the offspring, but merely supplying

1 The attempt to locate latent characters of organisms in particular parts of
the germ-cells should perhaps be regarded as a survival from a time when all
kinds of qualities, abstract or otherwise, were supposed to reside in definitely
restricted positions. Compare Phenology. The centres in the nervous system
are not comparable, since these are to be regarded as parts of mechanisms for
controlling different functions. The centres preside over the respective func-
tions, but the functions themselves are not located in the centres.

2 Boveri, "Em Geschlechtlich erzeugter Organismus ohne Miitterliche Eigen-
schaften," »S'. B. d. Ges. f. Morp/i. u. Phys., Miincktn, vol. v., 1889.

FERTILISATION 205

the material upon which the sperm operated.1 Seeliger,2 Morgan,8
and others have objected to Boveri's conclusion on the ground that
larviB arising from cross-fertilisation show an unusually wide range of
variation. Moreover, Godlewsky4 has carried out an experiment in
which he fertilised a non-nucleated portion of a sea-urchin's egg with
the spermatozoon of a crinoid, and obtained, as a result, a larva of
the maternal type. This experiment, if correctly described, se'ems
to nullify Boveri's conclusion.

Hickson has remarked that if it be true that the chromosomes
are the sole carriers of heredity it seems to be necessary to believe
in the individuality of the chromosomes ; that is to say, that the
chromosomes seen at the poles of the spindle at the termination of
mitosis are individually identical with those seen at the equator of
the spindle at the next mitosis. He points out, further, that there
is distinct evidence that this is not the case in certain Protozoa and
Coelenterata. Again, Hickson has called attention to the long
duration of the period of conjugation in Infusoria (Heterokaryota),
remarking that this is difficult to explain if we accept the view that
the cytoplasm of the conjugating cells is not concerned with the
transmission of hereditary characters.5

On the other hand, the persistence of parental chromosome groups
after fertilisation in many animals, and also the evidence of hetero-
genous hybridisation experiments, lend considerable support to the
theory of the individuality of the chromosomes, which gains more
ground every year. In Cyclops? Crepidula? Cryptobranchus,8 the two
parental groups of chromosomes after fertilisation are clearly distin-
guishable by their size and shape. Their peculiar characteristics are
retained through a number of successive cell divisions, the two sets
of chromosomes being always distinguishable on the equatorial plate
of the mitotic spindle. In Echinus, where the chromosomes number

1 The nuclei of such larvae have been shown to possess only half the normal
number of chromosomes ; see Morgan, " The Fertilisation of Non-nucleated
Fragments of Echinoderm Eggs," Arch.f. Entwick.-Mechanik, vol. ii., 1895.

2 Seeliger, " Giebt es Geschlechtlicherzeugte Organismen ohne Miitterliche
Eigenschaften ? " Arch.f. Enlwick.-Mechanik, vol. i., 1894.

3 Morgan, loc. cit. See also Wilson, loc. cit.

4 Godlewsky, " Untersuchungen iiber die Bastardierung der Echiniden und
Crinoiden-Familie," Arch.f. Entwick.-Mechanik, vol. xx., 1906.

6 Hickson, "The Physical Basis of Inheritance," British Assoc. Reports,
Leicester Meeting, 1907, and Tram. Manchester Micr. Soc., 1907. See also Fick,
"Vererbungsfragen, Reduktions- und Chromosomenhypothesen," Merkel und
Bonnets Ergeb. f. Anat. u. Phys., vol. xvi., 1906.

0 Haecker, "Ueber die Selbstandigkeit der vaterlichen und miitterlichen
Kernbestandteile wahrend der Embryonalentwicklung von Cyclops" Arch. f.
Mikr. Anat., vol. xlvi., 1895.

7 Conklin, "The Embryology of Crepidula" Jour. Morph., vol. xiii.,

I Ot7 / .

8 Smith (B. G.), " The Individuality of the Germ Nuclei during the Cleavage
of the Egg of Cryptobranchus," Biol. Bull., vol. xxxvii., 1919.

206 THE PHYSIOLOGY OF REPRODUCTION

about thirty-six, many of these have a distinctive shape in the form
of long or short pot-hooks, clubbed or V-shaped rods. According to
Baltzar,1 the same chromosomes can be identified over and over again
in successive segmentation divisions, by their peculiar shape. In
hybrid fishes obtained by crossing the salt-water minnow Fundulus
with the silver-sided minnow Menidia, Moenkhaus 2 could distinguish
the long chromosomes of Fundulus (which are about 2*18 /*) from the
short ones of Menidia (which are only \ p. in length) in all the
segmentation divisions. Morris3 even claims that in the cross between
Fundulus and the wrasse Ctenolabrus, the paternal and maternal
portion of the chromatin can be clearly distinguished in the resting
condition of the nuclei. In many other forms, as Sakamura4 has
recently shown in Vicia, certain of the chromosomes have definite
constrictions near their end and sometimes in the middle; these
constrictions appear in exactly the same position on these chromo-
somes in all successive cell divisions.

Verworn has objected on general grounds to the doctrine that
the hereditary transmission of parental characteristics is mediated
by the transference of nuclear substance only. This is what he
says : " The physiological mode of thought will hardly be able to
adapt itself to the idea of a single hereditary substance, which is
localised somewhere in the cell, and transferred in reproduction.
A substance that is to convey the characteristics of a cell to its
descendants, before all else must be capable of life, i.e. must have a
metabolism, and this is impossible without a connection with other
substances necessary to cell-metabolism, i.e. without the integrity of
all essential cell- constituents. The designation of a single cell-
constituent as the specially differentiated bearer of heredity is wholly
unjustified ; the cell protoplasm is of exactly the same value in this
respect as the nucleus, and we must constantly return to the fact
that in all living nature no instance is known in which a complete
cell possessing nucleus and protoplasm does not always mediate
hereditary transmission. The character of every cell is determined
by its peculiar metabolism. Hence, if the peculiarities of a cell are
to be transmitted, its characteristic metabolism must be transmitted ;
this is only conceivable when nuclear substance and protoplasm, with

1 Baltzar, "Die Chromosomen von Stronglocentrotu* lividus und Echinus
microtuberciilatus," Arch. f. Zellforsch., vol. ii., 1909.

- Moenkhaus, "The Development of the Hybrids between Fundulus
heteroclitus and Menidia notatus, with especial reference to the Behaviour of
Maternal and Paternal Chromosomes." Jour. Anat., vol. iii., 1904.

3 Morris (M.), "The Behaviour of the Chromatin in Hybrids between
Fundulus and Ctenolabrus" Jour. Eocp. Zool., xvi., 1914.

4 Sakamura, " Experimentelle Studien iiber die Zell- und Kernteilung
mit besonderer Biicksicht auf Form, Grosse, und Zahl der Chromosomen,"
Jour. Coll. Science, Imp. Univ. Tokyo vol. xxxix., 1920.

FERTILISATION 207

their metabolic relations, are transferred to the daughter-cells. This
is true of the sexual reproduction of the higher animals, as well
as of the asexual reproduction of unicellular organisms; in the
former, however, the metabolism of one cell, the spermatozoon, is
by the process of fertilisation combined with that of another cell,
the ovum, into a single resultant, the metabolism of the offspring
that arises from the fertilised ovum : the offspring hence possesses
the characters of the two parents." l

Morgan, in a work on the " Physical Basis of Heredity," z has
collected together the evidence that the chromosomes are the bearers
of the hereditary factors. He states that the embryological evidence,
while making out a strong case, is of itself insufficient to establish it,
but taken in conjunction with the genetic evidence derived from the
study of the sex chromosomes (see below, Chapter XV.) and
chromosome variation forces the conclusion that this view is correct.
On the other hand, Morgan recognises the occurrence of what he
calls " cytoplasmic inheritance," and says that the reactions by means
of which the embryo develops, and many physiological processes
are maintained, reside at the time in the cytoplasm " as the embryo-
logical evidence seems to indicate." Furthermore, there is also genetic
evidence to show that certain forms of inheritance are the outcome
of self-perpetuating bodies in the cytoplasm, most of which go
under the name of plastids. Eecognition of plastid inheritance
carries with it the idea that if there are such self-perpetuating
materials in the cytoplasm they will have to be taken into account
in any complete theory of heredity.

TELEGOSY

It used to be supposed that the spermatozoa of an animal on
being introduced into a female of the same kind, besides fertilising
the ripe ova and producing young, were capable of exercising a
permanent influence over the mother, and so transmitting certain of
their characters, not only to their own immediate offspring, but to
the future offspring of the mother by another sire. This phenomenon,3

1 Verworn, foe. cit. Cf. Farmer (loc. cit.), who regards the chromosomes of
the nucleus as representing primordia, which are responsible for the appearance
of the hereditary character's, but need to be supplemented by specific exciting
substances which determine what particular potential character shall actually
develop.

2 Morgan, The Physical Basis of Heredity, Philadelphia and London, 1920.

3 The phenomenon was explained by supposing that the young, while still
in utero, in some way affected the mother, and this influence was further trans-
mitted to the subsequent offspring. It will be seen that this explanation
assumes the possibility of the inheritance of acquired characters of which there
is little or no evidence. For recent reviews of this question see Morgan, Experi-
mental Zoology, New York, 1907 ; Thomson, Heredity, 4th Edition, London, 1920 ;
and MacBride, Science Progress, vol. xv., 1921. See also below, p. 209.

208 THE PHYSIOLOGY OF REPRODUCTION

in which many practical breeders still believe, was called Telegony
or Infection, and the female was said to be " infected " by the
previous sire.

The classical example, and one in which Darwin 1 himself believed,
of the supposed influence of a previous sire upon the future offspring,
is the case of Lord Morton's quagga, which was stated to have
infected an Arab mare, so that she subsequently produced two striped
colts by a black Arab horse. In recent years Ewart2 has repeated
the experiment, employing a Burchell's zebra and a number of
different mares. These experiments were supplemented by others in
which animals of various kinds were used. As a result of his
investigations he has come to the conclusion that there is no evidence
for the existence of Telegony. A microscopic examination of the
. structure of the hairs of the subsequent foals bred by Professor Ewart
provided further negative evidence.3 Minot,4 also, in a series of experi-
ments upon guinea-pigs, found no indication of any telegenic influence.
Moreover, Karl Pearson,5 as a result of an extensive statistical inquiry,
was unable to discover any evidence of telegony in man.6

EFFECT OF EXTERNAL CONDITIONS AND OF THE SOMA ON THE

GERM-CELLS

Attempts have been made by Stockard 7 and by Pearl 8 to modify

1 Darwin, The Variation of Animals and Plants under Domestication, Popular
Edition, vol. i., London, 1905.

- Ewart, The Penicuik Experiments, London, 1899.

3 Marshall, "On Hair in the Equidae," Proc. Roy. Soc. Edin., vol. xxiii., 1901.

4 Minot, "An Experiment with Telegony," British Assoc. Reports, Cambridge
Meeting, 1904.

'"' Pearson, The Grammar of Science, 2nd Edition, London, 1 900.

(i According to Kohlbrugge spermatozoa may penetrate the epithelium
of the uterine mucosa (in the mouse, rabbit, bat, etc.), and he suggests that they
may even unite with epithelial cells. These observations are advanced as a
possible explanation of Telegony. (Kohlbrugge, " Der Einfluss der Spermato-
zoiden auf den Uterus ; ein Beitrag zur Telegonie," Zeitsch. f. Morph. und
Anthrop., vols. xii. and xiii., 1910 and 1911.) Waldstein and Eckler maintain
that the absorption of spermatozoa is proved because after coitus in rabbits
the blood of the female develops a specific ferment directed against spermatozoa.
(Waldstein and Eckler, "Der Nachweis resorbieiten Spermas im weiblichen
Organismus," Wien klin. Woch., vol. xxvi., 1913.) The term "Xenia," which
means guestgifts (see Thomson, Heredity, London, 1920), was applied by
Focke to cases of plants in which the male pollen was supposed to affect the
ovarian tissue (the seed's substance or the fruit) rather than the embryo itself.
The term has also been applied to cases of birds where the colour of the egg
laid is said to be influenced by the cock. Thus canaries crossed by siskins,
linnets, or goldfinches are described by Tschermak (Biol. Centralbl., 1910) as
having the colour of the egg-shells modified by the male which fertilised the ova.

7 Stockard and Papanicolaou, "Hereditary Transmission of Degeneracy and
Deformities by Descendants of Alcoholised Mammals," Amer. Naturalist,
vol. 1., 1916, and Interstate Med.Jour., vol. xxiii., 1916.

8 Pearl, "On the Effect of Continued Administration of certain Poisons to
the Domestic Fowl, etc.," Proc. Amer. Phil. Soc., vol. lv., 1916.

FERTILISATION 209

the germ-cells of animals by giving alcohol by inhalation to the
parents. The young produced were often degenerate, paralytic or
deformed, especially the males, and the descendants of these offspring
are said to have been often worse than the first generation. Similar
experiments by Cole and Bachhuber,1 in which lead was administered
to male rabbits and fowls, are said to have resulted in a lowering of
vitality and a decrease in size on the part of the young. Fraenkel 2
states that the young of rabbits whose ovaries were subjected to
X-rays were stunted.

Ararious experiments have been carried out in which ova or
ovaries obtained from one animal have been transplanted into
another. Thus, Heape 3 successfully inserted the segmenting ova of
an Angora rabbit into the Fallopian tube of a Belgian hare, but
though the young developed in the uterus of the foster-mother,
there was no evidence that the latter influenced the characters of the
offspring. Guthrie,4 in experiments in transplanting the ovaries of
fowls of one variety into those of another, claimed to have proved
that the ova produced were influenced by the soma of the foster-
parents, since (for example) a black-plumaged hen supplied by
transplantation with an ovary from a white hen, when mated to a
white cock gave about equal numbers of white and spotted chickens.
Guthrie supposed that the black spots on the plumage of some of the
chicks showed that the black foster-mother had infected the engrafted
" white " eggs. Davenport,5 who repeated the experiments, came to
the conclusion that the transplanted ovaries never really became
functional, and that the eggs produced were derived from regenerated
ovaries that had not been completely extirpated.

On the other hand, Castle and Philips,6 who performed similar
experiments with guinea-pigs, state that the transplanted ovaries
yielded eggs which were afterwards fertilised, arid that the offspring
were unaffected by the soma of the foster-mothers. Thus, a white
guinea-pig into which an ovary from a black one was grafted,
when mated to a white male, gave .birth to litters of black
young ones.

1 Cole and Bachhuber, "The Effect of Lead on the Male Germ-Cells of the
Male Rabbit and Fowl, etc.," Proc. Exp. Biol. and Med., vol. xii., 1914.

2 Fraenkel, " Rontgenstrahlenversuche am tierischen Ovarien usw.," Arch.
f. Mikr. Anat., vol. Ixxx., 1912.

3 Heape, "On the Transplantation and Growth of Mammalian Ova
within a Uterine Foster-Mother," Roy. Soc. Proc., vol. xlviii., 1890, and
vol. Ixi., 1897.

4 Guthrie, "Further Results of Transplantation of Ovaries in Chickens,"
Jour, of Exp. Zool., vol. v., 1908.

5 Davenport, " The Transplantation of Ovaries in Chickens," Jour, of Morph.,
vol. xxii., 1911.

6 Castle and Philips, On Germinal Transplantation in Vertebrates, Carnegie
Institute (Washington) Publication, No. 144, 1911.

210 THE PHYSIOLOGY OF REPRODUCTION

ON GAMETIC SELECTION AND THE CONDITIONS FAVOURABLE FOR THE
OCCURRENCE OF FERTILISATION

It is a well-known fact in biology that, as a general rule,
conjugation occurs most readily between gametes belonging to the
same kind of organism. There are innumerable cases, however, in
which the spermatozoa of one species are capable of fertilising the
ova of another, and so initiating development. The resulting
embryo in such cases may grow into a mature hybrid offspring which
is not infrequently sterile (a fact which will be referred to again
later), or, on the other hand, owing to some mutual incompatibility
in the respective modes of growth inherited from the two parent
forms, the embryo may survive for a short time and then perish.

Cross-fertilisation can usually be induced most easily among
closely related species or among varieties belonging to the same
species. Thus, the different varieties of the frog, Rana fusca,
intercross as readily with one another as each variety fertilises its
own ova. On the other hand, the gametes of two species as widely
separate as the frog, Ranafusca, and the salamander, Triton alpestris,
have been known to conjugate, but the fertilised eggs so produced
divided irregularly and consequently failed to develop.1 In some
cases (e.g. the two species of frogs, It. fusca and R. arvalis) cross-
fertilisation can take place in one direction, but not in the reverse.
Pfliiger explained this result by supposing it to be due to peculiarities
in the shape or structure of the spermatozoa, those which have the
thinnest or most pointed heads being described as more successful in
inducing cross-fertilisation than those with large stout heads.2 This
explanation, while seeming to account for certain individual
instances, cannot be applied to all cases of cross-sterility.

Bataillon 3 has described experiments in which he fertilised the
eggs of Pelodytes and Bufo with the spermatozoa of Triton alpestris,
and obtained some degree of success, for the eggs in each case
underwent an irregular segmentation before they perished. The
spermatozoa underwent degeneration after conjugating, so that the
chromatin of the fertilised ova was derived entirely from the female
pronucleus. The experiments, therefore, afford additional proof that
spermatozoa in conjugating with ova perform a function altogether
apart from amphimixis (or the introduction of fresh chromatin
substance as a source of variation), and that this function is the
initiation of development.

1 Pfliiger, "Die Bastardzeugung bei den Batrachiern," PfliigeSs Archiv,
vol. xxix., 1882.

2 Pfliiger and Smith, " Untersuchungen iiber Bastardierung der Anuren
Batrachier, etc.," PfiiigeSs Archiv, vol. xxxii., 1883.

3 Bataillon, "Impregnation et Fecondation," C. K. de I' A cad. des Sciences,
vol. cxlii., 1906.

FERTILISATION 211

Among the Mammalia, as is well known, cross-fertilisation
between nearly allied species commonly occurs. The resulting
hybrid may be either sterile (e.g. the mule) or fertile (e.g. the hybrid
offspring of the bull and American bison). There is no evidence
that more widely separated species of Mammals can be induced to
have hybrid offspring. Spallanzani,1 by artificially inseminating an
oestrous bitch with the spermatozoa of a cat, attempted such an
experiment, but without a positive result.

A number of investigators have effected cross-fertilisation between
various kinds of Echinoderms. Vernon,2 who experimented with
forty-nine different combinations, obtained results which were more
or less successful in thirty-seven. In some of these, however,
development did not proceed beyond the blastula stage. Vernon
attempted to show that the capacity of the animal to transmit its
characters to its hybrid offspring depended upon the condition of
ripeness or staleness of its gametes at the time of fertilisation.
Thus, the spermatozoa of the sea-urchin, Strongylocentrotus, were
supposed to grow more and more " prepotent " as they became more
and more mature. Doncaster,3 however, has described further
experiments which seem to indicate that the variation in the form of
the hybrids obtained by Vernon was really due to differences in the
temperature of the water.

Shearer, de Morgan, and Fuchs 4 have been able to obtain an F,5
generation from the cross Echinus esculentus^. x E. acutusg at
Plymouth, but were unable to obtain fertile individuals of the cross
E. miliaris $ x E. esculentus £ or E. miliaris $ x E. acutnx $ although
fairly large and healthy F1 individuals of both these crosses were
reared. In all instances the gonads of the Fx crosses with E. miliaris
failed to develop beyond a very rudimentary condition. As the
result of extensive investigation of the early larval characters, these
authors come to the conclusion that they are too variable to afford any
trustworthy evidence of parental influence. This is particularly so

1 Spallanzani, Dissertations, English Translation, vol. ii., London, 1784. '

2 Vernon, "The Relation between the Hybrid and Parent Forms of
Echinoid Larvae," Phil. Trans., R, vol. cxc., 1898.

3 Doncaster, "Experiments in Hybridisation," Phil. Trans., B., vol. cxcvi.,
1903. MacBride ("Some Points in the Development of Ophiothrix fragilis"
Proc. Roy. Soc., B., vol. Ixxix., 1907) has recently shown that the immature
(ovarian) ova of the Ophiuroid, Ophiothrix, may be fertilised, but that the
subsequent development is abnormal, segmentation resulting in a morula
instead of a blastula, while at the stage at which the archenteron is formed,
there is a tongue of cells projecting into its lumen. It appears, therefore, that
the stage of maturity at which ova are fertilised may affect their embryonic
development if not their hereditary characteristics.

4 Shearer, de Morgan, and Fuchs, "On the Experimental Hybridisation
of Echinoids," Phil. Trans. Roy. Soc. Lond.t Ser. B., vol. cciv., 1914. See
also H. M. Fuchs, Jour. Mar. Biol. Ass., vol. x., 1914.

5 See footnote, p. 202.

212 THE PHYSIOLOGY OF REPRODUCTION

with regard to the skeleton, which has been used so extensively by
previous workers in this subject. In the late larval life, characters
such as the posterior ciliated epaulettes or ciliated rings are ones
that show very little variation and to which no exception can be
taken. E. esculentus and E. acutus always develop the posterior
ciliated epaulettes while E. miliaris never possess these structures.
In crosses between these forms conducted over three years, maternal
inheritance with regard to this character was invariably observed,
the reciprocals of a cross being unlike. In the fourth year's work,
however, the inheritance of this character proved different and gave
a dominance of E. esculentus and E. acutus over E. miliaris, both
reciprocals of a cross being alike. No reason for this change could
be suggested. The cytological study of material of all the crosses
during the course of the work showed that in all instances true
fusion of the pronuclei during fertilisation took place, but varying
amounts of chromatin were thrown out of the nuclei in different
crosses and in different experiments.

Loeb l discovered that cross-fertilisation of the eggs of Strojujylo-
centrotus by the spermatozoa of various species of starfish could be
effected by adding sodium carbonate or sodium hydroxide to the sea-
water in just sufficient quantity to render it slightly alkaline.
Under these conditions as many as fifty per cent, of the Strongylo-
centrotus eggs could be fertilised by Asterias spermatozoa, whereas in
normal sea-water cross-fertilisation between these two Echinoderms
only occurs very exceptionally. What the nature of the change is
whereby the alkaline sea-water enables the sperm to fertilise the ova
does not appear to be known. It has been observed that the
addition of the alkali increases the motive power of the sperms, but
the same result is brought about by bicarbonate of sodium, without
augmenting their capacity to cross-fertilise. Loeb suggests that the
entrance of the spermatozoon into the interior of the egg-protoplasm
may be due to surface-tension forces, and that the conditions for this
process may depend upon the surface tension between the sperma-
tozoon and the sea-water becoming greater than the sum of
the surface tensions between the sea-water and the egg, and the
spermatozoon and the egg. Loeb remarks, further, that the
fertilisation of Strongylocentrotus eggs by sperms of the same species
can best be accomplished in normal sea-water, and with this observa-
tion he associates the fact-that the mobility of the Strongylocentrotus
sperms is diminished by the alkaline water.2

1 Loeb (J.), " Ueber die Befruchtung von Seeigeleiern durch Seesternsamen,"
Pftiigei^s Archiv, vol. xcix., 1903. " Weitere Versuche iiber heterogene
Hybridisation bei Echinodermen," Pfltige^s Archiv, vol. civ., 1904. See also
translation of the latter, as well as other papers, in the University of
California Publications, Physiology, vols. i. and ii., 1902-4.

2 Loeb, The Dynamics of Living Matter, New York, 1906.

FERTILISATION 213

While suggesting that restrictions to the power of cross-fertilisation
may be due to differences in surface tension, Loeb admits that the
evidence seems to show that the capacity to conjugate is to some
extent at least specific. Attempts were made to fertilise the eggs of
sea-urchins with the spermatozoa of Annelids and Molluscs, but
these experiments were without success. Kupelweiser,1 however,
reports that he has been successful in fertilising Strong ylocentrotus
ova with the spermatozoa of the mussel (Mytilus), and that the
products developed into gastrulae.

Gray2 finds that the spermatozoa of Echinus miliaris in sea-
water are affected by positive trivalent ions such as those of Ce and
La, in much the same way as colloidal particles of albumen and
globulin. It is only those solutions that are capable of maintaining
the normal negative charge on the sperm unaltered that allow
vigorous movement of the sperm. Trivalent positive ions flocculate
sperm suspensions by lowering this negative charge. The action of
H' is very intense and changes the surface charge on the sperm from
negative to positive without any intermediate flocculation. The work
of Teague and Buxton3 shows that living cells (bacteria) are much
more sensitive to flocculation than dead cells or mastic particles.
Girard and Audubert4 claim that bacteria owe most of their
biological properties, .such as viability, pathogenetic power, etc., to
their surface charge.5 In the same way Gray suggests that the action
of H'-ion in bringing about the various effects found in heterogenous
hybridisation experiments is to be explained by the action of this ion
on the membrane charge of eggs and sperm. If sperm are placed in
sea-water to which a certain amount of acid is added, their surface
charge is reduced considerably below normal. Eggs put in the same
solution will have their charge altered to a different degree, and thus
the results of heterogenous hybridisation could be explained in a
simple manner.

Dr. A. T. Masterman tells me that, in certain cases, hybridisation
among fishes may be induced more readily in the absence of
opportunity for normal fertilisation, that is to say, for fertilisation

1 Kupelweiser, "Versuche iiber Entwickelungserregung und Membran-
bildung bei Seeigeleiern durch Mollusksperma," Biol. Centralbl., vol. xxvi.,
1906.

2 Gray (J.), "The Relation of Spermatozoa to Certain Electrolytes," II.,
Proc. Roy. Soc. Lond., Ser. B., vol. xci., 1920.

3 Teague and Buxton, "Die Agglutination in Physikalischen Hinsicht," III.,
Zeitsch. f. Physikal. Chem., vol. Ivii., 1906.

4 Girard and Audubert, " Les charges eUectrique des microbes et leur tension
superficielle," Compt. Rend. Acad. Science, vol. clxvii., 1918.

5 In the case of an asporogonous strain of Anthrax, the reduction of the
normal charge of the double electric layer (trd)from a value of 3'68 to 2'47 x 10~G
C.G.S., quintuples the normal growth of the culture, while by the reduction of
the value of o-d to 0, many pathogenetic bacteria are rendered harmless.

214 THE PHYSIOLOGY OF REPRODUCTION

of ova by spermatozoa of the same species. If such ova are present
the spermatozoa tend to conjugate with them rather than with ova
belonging to a different but closely allied species. It would appear,
therefore, that the spermatozoa exhibit an elective affinity for ova
belonging to the same species as themselves. This has been shown
especially in hybridisation experiments between brill and turbot.1

That assortative mating amongst gametes occurs generally as the
result of a preferential tendency possessed by them towards conjugating
with other gametes bearing similar characters to their own, and that
the comparative scarcity of hybrids in a state of nature is very
largely the result of this selective action, are facts with which many
of the older naturalists were familiar. With reference to the various
species of plants belonging to the family Composite, Darwin wrote
as follows : —

"There can be no doubt that if the pollen of all these species
could be simultaneously or successively placed on the stigma of any
one species, this would elect with unerring certainty its own pollen.
This elective capacity is all the more wonderful as it must have been
acquired since the many species of this great group of plants branched
off from a common progenitor."

Eomanes,2 who quotes this passage, remarks that " Darwin is here
speaking of ' elective affinity ' in its fully developed form, as absolute
cross-sterility between fully differentiated species. But we meet
with all lower degrees of cross - infertility — sometimes between
' incipient species,' or permanent varieties, and at other times between
closely allied species. It is then known as 'prepotency'3 of the
pollen belonging to the same variety or species over the pollen of
another variety or species, when both sets of pollen are applied to
the same stigma. Although in the absence of the prepotent pollen
the less potent will fertilise the seed, yet, such is the appetency for
the more appropriate pollen, that even if this be applied to the
stigma some considerable time after the other, it will outstrip or
overcome the other in fertilising the ovules, and therefore produce
the same result on the next generation as if it had been applied to
the mother plant without any admixture of the less potent pollen,

1 M'Intosh and Masterman, Life History and Development of the Food Fishes,
and articles in the Reports of the Scottish Fishery Boards, 9th Rep., Pt. III.,
10th Rep., Pt. III., and 13th Rep., Pt. III.

2 Romanes, Darwin and After Darwin, vol. iii., London, 1897. See also
Darwin, Animals and Plants, London, 1875, and Cross- and Self -Fertilisation in
Plants, London, 1876.

• 3 The term " Prepotency " is here used in a different sense to that in which
it is usually employed by zoologists, according to whom it means the greater
capacity of one parent, as compared with the other, to transmit its character!
to its offspring ; thus, instead of both parents transmitting their characters
equally, one may be "prepotent" over the other. (Cf. the Mendelian term
"dominant," which has a more precise signification ; see p. 199.)

FERTILISATION 215

although in some cases such incipient degrees of cross-infertility are
further shown by the number or quality of the seeds being fewer or
inferior."

It would appear, however, that when the aggregate vitality of the
ova and spermatozoa is reduced below a certain point, assortative
mating as a result of affinity between gametes bearing similar
characters no longer occurs. It thus happens that a reduction of
vitality is frequently correlated with an increased tendency towards
cross-fertilisation, which, on this view, is a source of renewal of
vitality. This theory was adopted to explain certain phenomena of
cross-fertilisation occurring among plants, by Fritz Miiller, who wrote
as follows : —

" Every plant requires for the production of the strongest possible
and most prolific progeny, a certain amount of difference between
male and female elements which unite. Fertility is diminished as
well when this degree is too low (in relatives too closely allied)
as when it is too high (in those too little related)." And, further,
" species which are wholly sterile with pollen of the same stock, and
even with pollen of nearly allied stocks, will generally be fertilised
very readily by the pollen of another species. The self-sterile species
of the genus Abutilon, which are, on the- other hand, so much inclined
to hybridisation, afford a good example of this theory, which appears
to be confirmed also by Lobelia, Passiflora, and Oncidium" l

Castle 2 found that the eggs of the hermaphrodite Ascidian, dona
intestinalis, could not, as a rule, be fertilised by spermatozoa derived
from the same individual, while they could be fertilised readily with
the spermatozoa of another individual. This rule, however, was not
without exceptions, for in some cases as many as fifty per cent, of
the eggs of one Giona could be fertilised with sperms of the same
individual, although this was very unusual. Morgan, who confirmed
Castle's observations, states that the failure to conjugate is due to
the inability of the sperms to enter the eggs. If the sperm succeeds
in entering, as in the exceptional cases, the fertilised egg develops
normally. Morgan found, further, that if the sperms are stimulated
to greater activity by alcohol, ether, ammonia, or certain salt solutions,
self-fertilisation may in some cases be induced. In another Ascidian,
Cynthia partita, Morgan observed that self-fertilisation frequently
occurs, but that the eggs in this species also are most usually
fertilised by spermatozoa from another individual.3 The foregoing

1 Miiller, "Investigations respecting the Fertilisation of Abutilon," English
Translation in American Naturalist, vol. viii., 1874.

2 Castle, "The Early Embryology of Ciona intestinalis" Bull. Mus. Comp.
Zool., vol. xxvii., 1896.

3 Morgan, " Self -Fertilisation induced by Artificial Means," Jour, of Exp.
Zool., vol. i., 1904. "Some Further Experiments on Self-Fertilisation in Cion.fi"
Biol. Bull., vol. viii., 1905.

216 THE PHYSIOLOGY OF REPRODUCTION

results of Castle and Morgan have been repeated by Fuchs,1 who
finds that, in Ciona, the self-fertilisation rate can be greatly increased
if concentrated sperm suspensions are employed. This rate can also
be much increased if a little egg extract is added to the sea-water
in which the fertilisation is carried out. The presence of the egg
extract has an immediate effect in raising the fertilisation percentage.
Extract of ovary or blood acts in the same way, the movements of
the sperm being greatly stimulated. The sperm of the sea-urchin
Strongylocentrotus is stimulated in the same manner by egg extract of
its own eggs or those of Sphcereckinus, Echinus, or Ciona eggs, but
Asterias egg extract completely inhibits the fertilising power of a
Strongylocentrotus sperm suspension. Fuchs has shown that a small
rise in the H-ion concentration of the sea- water brings about much
the same effect as the addition of egg extract, and, as a matter of
fact, the addition of egg extract to normal sea-water caused a slight
rise in its H-ion concentration.

Cohen2 lias shown that in sea- water in which the H-ion
concentration has been slightly raised above the normal, the life of
the sperm is greatly prolonged, and they are able to fertilise a
greater number of eggs.

It is well known that the fertility of animals which are much
in-bred is often reduced, but this is by no means invariably the case.3
Thoroughbred horses are notoriously in-bred, and it is interesting
to note that one of the earlier Reports of the Royal Commission on
Horse-breeding states that no less than forty per cent, of the
thoroughbred mares in this country fail to have foals each year.
This relatively large amount of sterility is probably due to a variety
of causes, and not entirely to the result of in-breeding.4

Low 5 has recorded an experiment on the effect of in-breeding in
fox-hounds. The particular strain is described as having perished
completely. Low states also that similar experiments have been
performed upon pigs, and, as a consequence, the litters became
diminished in size and frequency, while difficulty was often
experienced in rearing those which were produced.

1 Fuchs (H. M.), " Studies in the Physiology of Fertilisation," Jour, (lenetics,
vol. iv., 1915.

2 Cohen (E. J.), "Studies in the Physiology of Spermatozoa," Biol. Bull.,
vol. xxxiv., 1918.

3 The results of in-breeding are discussed at some length by Darwin,
Variation of Animals and Plants, vol. ii., Popular Edition, London, 1905. For

reviews of the subject see Morgan, Experimental Zoology, New York, 1907 ;
and East and Jones, In-breeding and Out-breeding, Philadelphia and London.
Pearl has worked out a mathematical formula for estimating the degree of
in-breeding, Amer. Nat., vol. xlvii., 1913.

4 Returns obtained by the Ministry of Agriculture show about the same
degree of fertility for cross-bred mares served by Shire stallions.

5 Low The Domesticated Animals of Great Britain, London, 1845.

FERTILISATION 217

Von Guaita,1 and Bos,2 in describing the effects of in-breeding
in mice and rats respectively, have recorded a steady decrease of
fertility in successive generations.

King,3 on the other hand, found no reduction in the fertility of
rats in-bred, for twenty-five successive generations, by brother and
sister mating.4

Castle and his collaborators,5 as a result of an investigation upon
the same question in the pumice-fly {Drosophila ampelophila), have
come to the conclusion that in-breeding tends to reduce the fertility
to a slight extent, whereas cross-breeding has a contrary effect. The
experiments showed further that in-breeding results in strains of
unequal fertility. The less fertile were eliminated by the product-
iveness being differential, so that only the more fertile persisted.
Moreover, whereas complete sterility was marked in the first part
of the experiment, in the later generations it has almost completely
disappeared. Moenkhaus,6 and others, in similar experiments on
in-breeding Drosophila, found likewise that though sterility increased
in the earlier generations the later ones were fertile.

East 7 interprets these results on the hypothesis that in-breeding
produces homozygous individuals (to use Mendelian terminology)
and that these when sterile are eliminated. He illustrates his
conclusions by reference to experiments on maize in which in-
breeding produces different results in different lines, showing that
segregation of certain factors influencing fertility has taken place.

1 Von Guaita, "Versuche mit Kreuzungen von verschiedenen Rassen der
Hausmaus," Ber. d. Xaturf. Gesell., Freiburg, vol. x., 1898.

2 Bos, " Untersuchungen ueber die Folgen der Zucht in engster Blutver-
wandtschaft," Biol. Centralbl., vol. xiv., 1894.

3 King, "Studies in In-breeding," Jour, of Exp. Zool., vol. xxvi., 1918.

4 Westermarck attributes the practice of exogamy (or marriage outside
the clan or family) in man to an instinctive aversion to marriage and sexual
intercourse between persons who have lived together closely through early
youth, and this mental characteristic is supposed to have arisen through natural
selection in view of the needs of the species which would suffer as a result of
in- breeding. In this theory Westermarck correlates "three parallel groups of
facts . . . the exogamous rules, the aversion to sexual intercourse between
persons living together from childhood, and the injurious consequences of
in-breeding" (The History of Huinan Marriage, 5th Edition, in three volumes,
London, 1921). Heape has a different theory of the origin of exogamy,
attributing it to the instinct which impels the errant male to seek a strange
female for his sexual gratification, and points out that when the pair are not
in accord the sexual stimulus for ovulation may not occur {Sex Antagonism,
London, 1913. See also Frazer, Totemism and Exogamy, London, 1911).

5 Castle, Carpenter, Clark, Mast, and Barrows, " The Effects of In-breeding,
etc., upon the Fertility and Variability of Drosophila" Proc. Amer. Acad. of Arts
(Hid Sciences, vol. xli., 1906.

6 Moenkhaus, "The Effects of In-breeding and Selection on Fertility,
Vigor, and Sex Ratio on Drosophila" Jour, of Morph., vol. xxii., 1911.

7 East and Jones, In-breeding and Out-breeding, Philadelphia and London.
This monograph contains a valuable discussion and numerous references to
literature.

218 THE PHYSIOLOGY OF REPRODUCTION

" Sterility in the form of structural degeneration when it occurs
gradually increases upon in-breeding until homozygosity is attained,
but for the most part it does not show any clear-cut segregation.
Yet reduction in fertility is noticeable only so long as there is a
change in other characters, constancy in visible characters being
accompanied by constancy in the matter of fertility. In other
words, there is no more an accumulation of sterility on continued
in-breeding than there is an accumulation of any other effect. Any
reduction in fertility ceases when homozygosity is reached, but the
end result may be decidedly different in various lines coining
originally from the same stock." In another passage East writes,
" While we are not justified in concluding . . . that in-breeding
accompanied by rigid selection will be beneficial [the experiments]
certainly show close mating is not invariably injurious."

The diminished fertility of in-bred animals may be due partly
to a decrease in the supply of mature ova perhaps correlated with
a general want of vigour. It seems possible, however, that it also
results from failure on the part of the gametes to conjugate, since
the productiveness of in-bred animals can often be increased by
cross-breeding with other varieties (see p. 639).

Heape l states that Dorset Horn sheep, when served by rams of
their own breed, show a greater tendency towards barrenness than
when served by Hampshire Down rams. It is possible that what
in this case appears to be barrenness is in reality very early abortion,
the in-bred embryos tending to die at an early stage and to be
absorbed in- utero, thus escaping observation.2 It seems not unlikely,
however, that, in the absence of cross-breeding, there is sometimes
an insufficiency of vitality at the very outset, the elective affinity
of the gametes being too feeble to induce conjugation.

Some years ago the writer carried out an experiment upon a
bitch belonging to the Dandie Dinmont variety, which is known to
be very in-bred. Seminal fluid was obtained from a pure-bred Dandie
Dinmont dog, and also from an obviously mongrel terrier of unknown
ancestry. The semen from the two dogs was examined micro-
scopically, and in each case was found to be rich in sperms, which
so far as seen were all moving and in a vigorous condition. Approxi-

1 Heape, "Abortion, Barrenness, and Fertility in Sheep," Jour. Royal A(//-i<:
Soc., vol. x., 1899.

2 Hammond ("On Some Factors Controlling Fertility in Domestic Animals,"
Jour, of Agric. Science, vol. vi., 1914), who has described the common occurrence
of degenerative foetuses in the uterus of the sow, suggests that this may be the
result of " lethal factors " intensified by in-breeding in the manner postulated
by East. Kirkham (" Embryology of Yellow Mouse," Proc. Amer. Soc. ZooL,
Anat. Record, vol. xi., 1917) and Ibsen and Steigleder ("Evidence of the Death
in utero of the Homozygous Yellow Mouse," Amer. Nat., vol. li., 1917) have
supposed that homozygous yellow mice, which are never born, but seem
invariably to die in the uterus, carry a " lethal factor."

FERTILISATION 219

mately equal quantities of each sample of semen were then mixed
together in a glass tube. After a further examination of the mixture,
when it was observed that all the sperms were still active, the fluid
was injected into a pure-bred Dandie Dinmont bitch, which was
distantly related to the Dandie Dinmont dog. Previously to the
experiment the bitch had been kept apart from other dogs, and this
restriction was continued so long as she showed signs of oestrus.
Fifty-nine days after the injection the bitch littered four pups,
which closely resembled one another. Of these one died early, but
the other three grew into mongrels which somewhat resembled the
terrier sire, so that there can be little doubt that all four pups
were mongrels. No stress should be laid upon the result of a single
experiment; but the evidence, such as it was, was indicative of a
selective tendency, consequent upon a reduced vitality, on the part
of the ova of the in-bred animal to conjugate with dissimilar rather
than with related spermatozoa.

Professor Ewart has informed the writer of a case in which a
Dandie Dinmont bitch in his possession copulated with a dog
belonging to the same breed, and two days subsequently had inter-
course with a Scotch terrier. In due time the bitch littered three
pups, and of these only one was a pure-bred Dandie Dinmont, while
the other two were half-bred Scotch terriers, in spite of the fact
that the Dandie Dinmont dog copulated two days earlier than the
Scotch terrier. This case may be regarded as to some extent
confirmatory of the experiment described above.1

Doncaster,2 in describing his experiments on Echinoid hybridisa-
tion, states " that cross-fertilisation is assisted by conditions which
tend to reduce the vitality of the eggs." This artificial reduction
of vitality could be accomplished either by warming the eggs, or by
shaking them, or by keeping them for several hours, or by placing
them for from one to two hours in diluted sea-water, the last method
being the most uniformly conducive to the occurrence of cross-

1 Seeing that an assortative mating of gametes can probably occur between
the ova of one individual and the spermatozoa derived from different individuals,
whether as a result of gametic similarity or reduction of vitality, it is not
improbable that gametic selection also sometimes takes place when various
gametes of a single individual are bearers of different characters, in the manner
postulated by the Mendelian theory. Such a preferential mating, if it exists,
would of course obscure the evidence of that very gametic segregation, the
probable existence of which, in other cases, is inferred from the numerical
proportions in which the different sorts of zygotes or offspring are produced ;
for if there is an assortative mating among the gametes, it is obvious that the
offspring would no longer be produced in definite Mendelian proportions, since
these depend upon the chance unions of gametes. According to this view,
prepotency may perhaps be interpreted as the tendency of the gametes of an
individual to conjugate with other gametes bearing similar hereditary
characters.

2 Doncaster, loc. cit.

220 THE PHYSIOLOGY OF REPRODUCTION

fertilisation. There is some evidence, therefore, that a reduction
of vigour among the gametes, whether occurring naturally as a
consequence of in-breeding or produced artificially as in Doncaster's
experiments, may lead to a similar result, since both conditions may
bring about an increased tendency towards the union of dissimilar
gametes. On another view, the tendency towards cross-fertilisation
in Doncaster's experiments may be looked upon as evidence of a
diminished power of resistance, on the part of the ova, to the
entrance of foreign spermatozoa, consequent upon a reduced vitality
in the ova.1

Further evidence upon this question is afforded by studying the
Protozoa (see also pp. 639-642).

CONJUGATION ix THE PROTOZOA

The phenomenon of conjugation in the Protozoa possesses a
special interest, inasmuch as it is undoubtedly the forerunner of
fertilisation in the Metazoa. It is clear, therefore, that a complete
understanding of the changes which attend the former process
cannot fail to throw great light on the nature and significance of
gametic union in multicellular organisms.

In the different groups of Protozoa all gradations are to be found
between the conjugation in the general sense (i.e. the union, either
temporary or permanent, of two similar unicellular organisms), and
a process identical with metazoan fertilisation. Thus, in the peri-
trichous Ciliata there is a pronounced sex differentiation in the size
and activity of the gametes, which clearly correspond to ova and
spermatozoa. Even the maturation phenomena, which play so
important a part in the developmental history of the metazoan
gametes, are represented in some sort by comparable processes which
have been observed in certain Protozoa.2 There can be no doubt,
therefore, as to the essential similarity of conjugation in unicellular
organisms and fertilisation in multicellular ones.

Raymond Pearl,3 as a result of a biometrical study of the process
of conjugation in Pdram&cinm caudatum, has arrived at the conclusion
that in this protozoon there is a definite tendency for like individuals

1 It may be mentioned also that Loeb has shown that, whereas mature
starfish eggs soon die if fertilisation is prevented, eggs in which maturation
is artificially hindered through lack of oxygen or the addition of an acid to
the sea- water, remain alive much longer than when allowed to become mature.
(Loeb, "Maturation, Natural Death, and the Prolongation of the Life of
Unfertilised Starfish Eggs, etc.," Biol. Buff., vol. iii., 1902.) It would appear,
therefore, that the mature eggs have suffered a loss of vitality which ordinarily
can only be increased by the act of fertilisation.

2 See Enriques, loc. cit. See footnote, p. 198.

3 Pearl, "A Biometrical Study of Conjugation in Paramoecium" Biometreika,
vol. v., 1907.

FERTILISATION 221

to mate with like, since there is a considerable degree of hornogamic
correlation both between the lengths of the conjugant pairs and also
between their breadths. Evidence is presented to show that the
homogamic correlation arises through the necessity for the anterior
ends and mouths of the two individuals to " fit " reasonably well in
the act of successful conjugation. If this is so, the necessity for
assortative mating in Paramcecium is purely mechanical, and the
principle involved is not of general application to other gametic
organisms. Pearl states, also, that there is no evidence that
conjugation tends to produce increased variability in ex-conjugants.
On the contrary, there are indications that conjugation tends to
restrict the existing variability induced by environmental influences ;
or, in other words, to preserve a relative stability of type. This
conclusion is antagonistic to Weismann's hypothesis referred to
above (see footnote, p. 198).

As already mentioned, the reproductive processes in the Protozoa,
like those in the Metazoa, tend to run in cycles, each cycle beginning
and ending with an act of conjugation. Maupas' observations
showed that in various genera of Infusoria (Paramcecium, Stylonychia,
etc.) a long period, during which the animals multiply by simple cell
division, is succeeded by a period when conjugation is of very
common occurrence. This marks the commencement of a new cycle,
being physiologically comparable to the period of sexual maturity
in multicellular organisms. If conjugation were prevented from
occurring, the individuals gradually ceased to divide and under-
went changes which invariably led to death. As a result of
these experiments, Maupas arrived at the conclusion that the
purpose of conjugation is to counteract the tendency towards
senile degeneration, and to bring about a rejuvenescence or renewal
of vitality.1

Maupas' observations have been confirmed by Joukowsky2 and
Simpson,3 and more particularly by Calkins.4 The last investigator
found, further, that the periodic seasons of " depression " or loss of
vitality which invariably occurred if conjugation were prevented,
and which normally resulted in the cessation of cell division and

1 Maupas, " Recherches experimentales sur la Multiplication des Infusories
Cili«3S," Arch, de Zool. Exp. et Gen., vol. vi., 1888. " Le Eajeunissement
Karyogamique chez les Cilies," Arch, de Zool. Exp. et Gen., vol. vii., 1889.

2 Joukowsky, " Beitrage zur Frage nach den Bedingungen der Vermehrung
und des Eintrittes der Konjugation bei den Ciliaten," Verh. Nat. Med. Ver.,
Heidelberg, vol. xxvi., 1898.

3 Simpson (J. Y.), " Observations on Binary Fission in the Life-History of
the Ciliata," Proc. Roy. Soc. Edin., vol. xxiii., 1901.

4 Calkins, " Studies on the Life-History of Protozoa," IV., Jour, of Exp.
Zool., vol. i., 1904. References to earlier papers are here given. See also Biol.
Bidl, vol. xi., 1906, and Amer. Nat., vols. xlix. and 1., 1915 and 1916.)

222 THE PHYSIOLOGY OF REPRODUCTION

ultimately in death, could be tided over and the race carried through
further cycles of activity by having recourse to artificial stimuli in
the medium surrounding the culture. In a series of experiments,
which Calkins conducted for twenty-three months with a single race
of Paramoecium, it was found that periodic reductions of vitality
occurred at intervals of about six months. At such times the race
under cultivation would have died out entirely had it not been for
the application of stimuli in the form of extracts of various food
substances (beef, pancreas, brain, etc.). With the assistance of these
restoratives, on three separate occasions, this particular race of
Paramoecium was carried through four cycles of activity and 742
generations without the occurrence of conjugation. It thus appears
that a change in the environment may result in a rejuvenescence of
the race.

As a consequence of these experiments, Calkins has suggested
that the purpose of conjugation may be to bring about the union of
individuals which have lived in different environments, and so to
produce a renewal of vitality in the same kind of way as a change in
the environment itself.

Calkins differs from Maupas in stating that diverse ancestry is
not essential in order that conjugation may occur, since he obtained
as large a percentage of successful endogamous as exogamous
pairings, and carried one endogamous ex-conjugant through 379
generations. On the other hand, there is some evidence that
conjugation does not result in rejuvenescence when both gametes
have lived for a long time in the same medium, so that their chemical
composition is too similar.1

According to Enriques, however, conjugation in Colpoda steini
only takes place under certain environmental conditions (e.g. if the
layer of the water is not thicker than two millimetres) and does not
occur at all if the conditions of life are stationary, the infusorians
going on multiplying indefinitely and the number of divisions from
the last conjugation making no difference.2 According to Woodruff,3

1 Cull, "Rejuvenescence as a Result of Conjugation," Jour, of Exp. ZooL,
vol. iv., 1907. Blackman ("The Nature of Fertilisation," British Assoc. Reports,
York Meeting, 1906) is of opinion that the rejuvenescence theory of fertilisation
is difficult to apply generally in view of the large number of plants in which
the fusing cells or nuclei are closely related. The force of this objection must
be admitted. If, however, the conjugating cells have been subjected to slightly
different environmental influences, this near relationship is not necessarily a
difficulty.

2 If water from a culture in which conjugation is " epidemic " be added to a
normal culture, it is stated to induce conjugation. Conversely, if water from
a normal culture is added to a "conjugation culture" it inhibits it.

:! Woodruff, "The Life-Cycle of Paramoecium when Subjected in Varied
Environment," Jour, of Exp. ZooL, vol. xlii., 1908. Jennings, "The Effect of
Conjugation in Paramoecium," Jour, of Exp. Zool., vol. xiv., 1913.

FERTILISATION 223

on the other hand, a varied environment seemed to obviate the
necessity for conjugation in Paramcecium.

He was able by continually altering the character of their food,
and imitating the conditions of pond life, to continue the life of a
single race of Paramcecium for over five years, and carry it through
3000 generations by simple fission without conjugation taking place.1
Many of these cultures showed periods of depression followed
by periods of increased fission, and further investigation showed that
each period of depression and restoration was accompanied by a
special process of nuclear reorganisation which apparently replaced
the act of conjugation. The macronucleus breaks up and disappears,
the micronuclei dividing twice, but do not complete the third division,
which in conjugation gives rise to the gametic nuclei. A new
macronucleus is formed from the micronuclei, and the normal nuclear
organisation re-established in this way. To this process of nuclear
reorganisation Woodruff has applied the name of " endomians." The
question of endomixis has been studied by Erdmann,2 who comes to
the conclusion that new lines of Paramcecium originate after this
process, and are made constant by selection ; that is, heritable
variations occur in asexually conducted lines, and that the rigid
conception of the ganotype does not hold true for Protozoa. If a
pure line of Paramcecium is transferred to new environmental
surroundings, it answers immediately to this change by the pro-
duction of endomixis. The necessary opportunity is then given
for the survival of those individuals of the new stock in equili-
brium with their new surroundings. This process is constantly
taking place in nature, for if a roadside pool partially dries
up, or a heavy fall of rain takes place, its chemical character
may be altered, but the Paramwcia inhabiting the pool are
enabled to adjust themselves to the change through the process-
of endomixis.3

It may seem a far cry from the Ciliate Infusorian to the British
thoroughbred horse, yet there is evidence that here also an in-bred
and relatively infertile race may be rejuvenated through access to new
surroundings. Allison, referring to blood stock of British origin,
born in Australia and New Zealand, writes as follows : " We can
draw from these, not only strains of blood which we have lost, but
horses and mares, born again, so to speak, and admirably suited to

1 Woodruff, "Rhythms and Endomixis- in Various Races of Paramoecium
aurelia" Biol. Bull., vol. xxxiii., 1917 ; see also Woodruff and Erdmann,
"Abnormal Periodic Reorganisation Process without Cell Fusion in Para-
moscium" Jour, of Exp. ZooL, vol. xvii., 1914 ; and Jennings, loc. cit.

2 Erdmann, "Endomixis and Size Variations in Pure Bred Lines of
Paramascium aurelia" Arch. f. Entwick. d. Organism, vol. xlvi., 1920.

3 Mr. Saunders informs me that in England roadside pools frequently
undergo great changes of H'-ion concentration after rain storms.

224 THE PHYSIOLOGY OF REPRODUCTION

strengthen and regenerate our home stock." x The same result is
said to have been achieved in the descendants of British horses
(especially Hackneys) imported into Argentina.2

The case of the Porto Santo rabbits and that of the goats of Juan
Fernandez, which are cited by Huth 3 as evidence that in-breeding is
harmless, may perhaps be similarly explained.

Moreover, such an interpretation is not necessarily inconsistent
with the genetic explanation given by East and Jones (see above,
p. 218), according to whom the infertility may be due to adverse
factors in certain strains, since the environment may exercise an
effect on the germ-plasm through the body cells and so produce a
selective influence.

It would seem on the whole that the only feature common to
conjugation or fertilisation throughout the animal kingdom is
biparental inheritance. The association of fertilisation or conjugation
with reproduction is not an essential one ; as it is not universal it can
hardly be a necessary relationship. In Paramcecium, as we have just
seen, nuclear reorganisation can bring about a fresh cycle of fission
equally as well as conjugation. In the higher phyla of the animal
kingdom the close association of fertilisation with reproduction has
completely obscured their primitive relationships and significance.

THE SUPPOSED CHEMOTACTIC PROPERTIES OF SPERMATOZOA AND
THEIR RELATION TO THE PHENOMENA OF FERTILISATION

It has been suggested that the spermatozoon is attracted towards
the ovum by a chemotactic action which the metabolic products of
the latter are able to exert upon the former. Pfeffer's experiments 4
upon the spermatozoa of ferns are usually cited as evidence of this
view.

Pfeffer observed that malic acid, when put into a capillary tube
with one end open and placed in a drop of liquid containing fern
spermatozoa, has a strong attractive influence upon these organisms,
causing them to swim in large numbers into the opening of the tube.
He concluded, therefore, that it is the malic acid in the archegonium
of the fern's ovum which causes the approach of the spermatozoa.

According to Strasburger,5 the ova of the Fucacete also possess
chemotactic properties, attracting the spermatozoa from a distance

1 Allison, The British Thoroughbred Horse, London, 1901.

2 Wallace (B.), Argentine Shows and Livestock, Edinburgh, 1904. Cf. also
Darwin, Animals and Plants, London, 1905.

3 Huth, The Marriage of Near Kin, 2nd Edition, London, 1887.

4 Pfeffer, " Locomotorische Bichtungsbewegungen durch chemische Beize,"
Vntersuchungen atis. d. Bot. Inst. zur Tubingen, vol. i., 1884.

5 Strasburger, Das botan. Prakticiim, Berlin, 1887.

FERTILISATION 225

equal to about two diameters of an ovum. Bordet,1' however, who
likewise experimented upon the Fucacene, obtained no evidence of
chemotactic attraction, but he found, on the other hand, that the
sperms were very sensitive to contact.

Jennings,2 in the course of his experiments on the behaviour of
the Protozoa, has shown that these organisms will tend to collect in
a drop of acid placed in water. This is due to the fact that, wrhereas
no reaction takes place when the individuals pass from water to
acid, there is a distinct reaction in passing in the reverse direction.
All the organisms which enter the drop of acid remain there, and
consequently they accumulate, but this is not due to any attractive
influence on the part of the drop. It is of course possible that
Pfeffer's observations on the supposed attraction possessed by
malic acid for the spermatozoa of ferns is susceptible of a similar
explanation.

Buller,3 who has discussed the question at some length and has
performed numerous experiments, states that, so far as he is aware,
not a single case is known where chemotaxis plays a part in the
fertilisation of the ova of animals.

CHILD'S THEORY OF THE LIFE CYCLE 4

Child,5 as the result of some twenty years' study of the process
of regeneration in many animals, and especially with regard to
Planarians, has brought forward a theory of the life cycle in plants
and animals, which is of remarkable interest on account of its
many applications. In this theory an attempt has been made to
break away completely from the corpuscular conception of the
development and inheritance of the organism, which in the past
thirty years has dominated all our outlook on this subject. In
the following remarks this theory can only be considered in relation
to the origin of the gametes, fertilisation, and the problem of the
life cycle, very briefly.

In the animal kingdom there are two well-established mean's of
reproduction, which in many groups such as the Hydromedusie
alternate with one another, or entirely replace each other, as in
some of the lower worms. First, we have asexual reproduction

1 Bordet, " Contribution a 1'Etude de 1'Irritabilite des Spermatozoides chez
les Fuccacees,"/?«W. de I'Acad. Belgique, vol. xxxvii., 1894.

2 Jennings, " Studies of Reactions to Stimuli in Unicellular Organisms,"
Amer. Jour of Physiol., vol. xxi., 1897.

3 Buller, "Is Chemotaxis a Factor in the Fertilisation of the Eggs of
Animals ? " Quar. Jour. Micr. Science, vol. xlvi., 1902.

4 By C. Shearer.

6 Child's views have been put forward in Senescence and Rejuvenescence,
Univ. Chicago Press, 1915 ; also in a smaller work, Individuality in Organisms,
Chicago, 1915. To these the reader is referred for further information.

8.

226 THE PHYSIOLOGY OF REPRODUCTION

by fission or budding, which is usually considered the oldest form
of reproduction. In some worms, such as Planaria velata, Ctenodrttus
monostyhis,1 this seems to be the sole means of reproduction which
these animals possess. Secondly, we have reproduction by means of
gametes, and their fusion to form the zygote or fertilised egg. These
two modes of reproduction are essentially similar in many respects,
and one has probably been derived from the other in the course of
evolution. In many Planarians, any part of the body may give rise
to a new individual, provided this portion of the body becomes
isolated to a certain extent, or entirely separated from the parent
body. Thus Planaria velata, at the end of the season, breaks up
into a large number of minute fragments, which contract into round
spherical masses not unlike ova in appearance, and the following
year give rise to new worms. The gametes or germ-cells are
comparable, in Child's opinion, to these fragments of Planaria vein In,
and are therefore physiologically old cellsj differing in no way from
other cells of the body, except that they require conjugation with
one another, in order to undergo reorganisation and rejuvenation,
but still in many instances they are able to undergo this process in
the absence of conjugation or fertilisation, as in parthenogenetic
development. Child arrives at this conclusion as the result of a
long series of investigations into the metabolic growth rate of
regenerating worm fragments, and the investigation of the metabolic
rate at different periods of the animal life cycle. To determine this
rate certain tests are employed. In an aqueous solution of potassium
cyanide or weak alcohol, in which death of the worm fragment or
egg-cell occurs in from a few minutes to several hours, the sus-
ceptibility varies with the metabolic rate ; thus in a fragment in
which the metabolic rate is high, as shown by its consumption of
oxygen, or output of C02, or its functional activity, the susceptibility
is also very great, and all conditions which increase metabolic
activity increase susceptibility. If, however, the narcotics are used
in such low concentration as to admit of partial, but not complete
tolerance to the new conditions, then those fragments of the worm
in which growth is most rapid and the metabolic rate is highest
are the last to be killed, as they have the greatest power of
adjustment to the action of the narcotic. This method is the
reverse of the first, and may be called the indirect susceptibility
test. By the application of these tests and others of a similar
character, in which potassium permanganate or phenylurethane
are used, Child has shown that the growing organism possesses
definite axial growth gradients, in which the metabolic rate is

1 Monticelli has described a sexual phase in this animal. Atti del Congresso
dei Naturalisti italiani, 1906, Milan, 1907.

FERTILISATION 227

many times greater than in other parts of the animal. An investi-
gation of these gradients has furnished him with information which
has made possible the experimental control of morphogenesis and
the development of specific form in the Planarian, perhaps the most
remarkable triumph in the annals of recent biological research.

In the Planarian, the study of these gradients shows that the
metabolic processes are most active in the head region and that they
diminish as we pass down the main axis of the worm, being lowest
in the tail region. Those portions of the worm having the highest
rate control those with a lower rate. If by transverse section we
cut off the head and tail of a Planarian, the frequency with which it
will regenerate a new head at one end x of the remaining portion of
the worm, will be in direct relation to the height of the metabolic
rate at this end x, and in inverse relation to the metabolic rate at
the other end of the piece y. If x is higher than.y, then a head will
form at x, if y is higher than x, a head will form at y. If x and //
have about the same metabolic rate, then we will have even chances
that a head or tail will form at x or y. Now the metabolic rate at
x and y can be decreased or increased at will by certain reagents, or
functional activity, and so a head can be made to appear where,
under less stimulation, a tail would normally regenerate, and thus
the process of regeneration can be definitely controlled.

The study of the unfertilised egg-cell shows that its metabolic
rate is low, and the evidence discussed in one of the foregoing
sections amply testifies to this, in the astoundingly small oxygen
consumption of the unfertilised egg. On fertilisaton a considerable
increase of susceptibility takes place, which in Nerds reaches its
height when the free-swimming stage is attained, while in Arcnicola
it is only reached when the young worm has developed five or six
segments. In the' sea-urchin Arlacia, and the starfish Asterias, the
metabolic rate as determined by the direct susceptibility test reaches
its highest level at the gastrula stage, and from this onwards slowly
decreases, rejuvenescence comes to an end and old age begins. In
Vertebrates much the same thing holds, in Fundulus rejuvenescence
occurs during the early stages of development, but as soon as the
periblast forms and the embryo assumes its shape, senescence
commences. In the wrasse Tciutogolabrus, the period of increasing
susceptibility continues up to the time of hatching, and so to a much
later stage than in Fundulus. In the frog and the salamander the
average susceptibility increases from fertilisation onwards through
segmentation and gastrulation to the formation of the embryo and
somewhat beyond the hatching stage; after this senescence coin-,
mences. The animal life cycle is therefore a more or less brief
period of rejuvenescence followed by a longer and more gradual

228 THE PHYSIOLOGY OF REPRODUCTION

stage of senescence, in which the organism slowly grows old. Its
functions come to an end through the gradual accumulation of
metaplastic substances in the cytoplasm of its cells which finally
bring about death. The cycle is restarted by the production of
buds or germ-cells by the old organism which are capable of
rejuvenescence, so the repetition of the- cycle is rendered possible.
It results from this conception of the life cycle that no special
weight need be given to the many peculiar features connected with
the origin and supposed segregation of the germ-cells, to which
the Weismann theory of the germ-plasm has attached such great
importance. Child has shown that in the Cestode Moniezia, under
certain conditions, the spermatagonia can be differentiated from
somatic muscle-cells, and that a germ-plasm with a given specific
constitution does not hold in the case of this animal. Many of the
facts of experimental embryology and regeneration, moreover, clearly
render the old theory of the germ-plasm untenable. It is, however,
in the explanation of those peculiar types of development in which
we find pcecilogonie, peedogenesis, and dissogonie taking place that
Child's theory gives us such assistance ; under no other theory can
these conditions be reduced to any semblance of order or meaning.1

In a recent paper Stockard 2 has brought forward many
interesting facts that throw new light on the question of the
development of specific form in animals. Thus by arresting the
development of fish embryos at various stages of growth, by keeping
them at low temperatures (temp. 5° C.) for a short time, definite
abnormalities, such as twin or triple monsters, could be produced.
There was a more or less constant relation between the abnormality
produced, and the particular stage at which the embryo had been
placed in the cold. An embryo kept in the cold at an early stage
would subsequently, on being returned to normal temperature,
develop into a twin monster; placed in the cold at a later stage

1 The term Pcecilogonie has been introduced by Giard ("La Pcecilogonie,"
17. Cong res Int. d. Zol. a Bern, 1904) to describe that condition where an

animal possesses two quite different modes of reproduction, such as that shown
by the fly Musca corvina, which in the North of Europe reproduces by means
of a large number of eggs, while in the South it is viviparous, both types of
development resulting in the same adult. Pcedogenesis is a term first introduced
by von Baer (Bull. Ac-ad. Imp. St. Petersburg, vol. lx., 1866) where reproduction
is carried on by the larva and not the adult, as for instance in the Chironomus
larva, which lays eggs that give rise to a perfectly functionless adult gnat.
Dissogonie is a term first used by Chun ("Die Dissogonie, eine neue Form
der geschlechtlichen Zeugung," Festschrift, f. Leuckart, 1892), and describes that
condition where the animal produces ripe gametes in both the embryonic or
larval condition and again in the adult stage, as for example in certain
Ctenophores such as Bolina hydatina and Euchans mvlticornis.

2 Stockard, " Developmental Kate and Structural Expression : An experi-
mental study of twins, ' double monsters ' and single deformities, and the
interaction among embryonic organs during their origin and development,"
Amer. Jour. Anat., vol. xxviii., 1921.

FERTILISATION 229

of development, it would respond only by forming a double head.
Lack of proper oxygen supply also brings about abnormal develop-
ment in fish embryos. In Mammals, where we sometimes get
polyembryony, it is suggested that an insufficient supply of oxygen
to the ovum might produce this condition. The fertilised ovum
travelling down the Fallopian tube probably receives an abundant
supply of oxygen; arriving in the uterus in certain animals it
apparently rests some time before it becomes fully implanted and
the chorionic layer is formed and a free supply of oxygen from the
maternal circulation is established, and such a condition might lead
to polyembryony. In some animals, as the opossum and the
armadillo, polyembryony would seem to be the normal mode of
reproduction. In the armadillo, at least, development stops for
several weeks after the blastocyst reaches the uterus, and during this
time it lies perfectly free in the uterus, without any supply of
oxygen from the maternal circulation.

Newman l has brought forward in a recent book many facts
of a similar character.

ARTIFICIAL AIDS TO FERTILISATION

It has been already recorded that cross-fertilisation between
certain species of Echinoderms can be effected by having recourse
to physico-chemical methods. It is not surprising, therefore, that
fertilisation between individuals belonging to the same species can
be assisted, or caused to take place more frequently, in the presence
of certain substances artificially added.

Thus, according to Eoux, frogs' eggs can be fertilised more readily
by adding saline solution to the water in which they are deposited.
Wilson says that in the case of the mollusc Patella, a larger number
of eggs can be fertilised if potash solution is added.2 Dungern3
states that the activity of the spermatozoa in the sea-urchin can be
increased in the presence of substances extracted from the qva.
Similarly it is said that normal prostatic secretion lias an exciting
action on mammalian spermatozoa (p. 248). Furthermore. Torelle
and Morgan 4 have shown that the immature spermatozoa of starfish
can be stimulated, and fertilisation can be induced, by adding ether
and various salt solutions to the sea- water (see also p. 216).

1 Newman, Thi> Biology of Twim, Chicago Press, 1917.

2 For further information on this subject, with references to literature, see
Przibram, Embryogein/, English Translation, Cambridge, 1908 ; and Jenkinson,
Experimental Embryology, Oxford, 1909.

3 Dungern, "Neue Versuche zur Physiologie der Befruchtung," Zeitsch. f.
allgem. Phys., vol. i., 1902.

4 Morgan, Experimental Zoology, New York, 1907.

230 THE PHYSIOLOGY OF REPRODUCTION

PARTHENOGENESIS, NATURAL AND ARTIFICIAL1

The fact that the ova of various kinds of organisms are capable
under certain circumstances of segmenting and developing into new
individuals without the intervention of male germ-cells, has been
already referred to. In such animals as the Aphidte this method
of reproduction appears to be called forth by certain conditions of
temperature and moisture. In other forms of life the necessary
factors for the occurrence of parthenogenesis are not so evident, but
the fact of its existence has been known from early times.

In many animals parthenogenesis has been observed to occur
occasionally, although it may never have become a confirmed
physiological habit. The silkworm moth (Bomlyx mori) affords an
example of this phenomenon. In the higher animals also it has
been shown that unfertilised eggs may very abnormally start to
segment without any obvious source of stimulus. Janosik2 has
recorded segmentation in the ovarian ova of Mammals, but it is
doubtful whether such cases should be regarded as truly partheno-
genetic in nature.

Tichomiroff 3 showed that the unfertilised eggs of the silkworm
moth, which, as just mentioned, is occasionally parthenogenetic, can
be caused to develop in greatly increased numbers by rubbing them
lightly with a brush, or by dipping them for about two minutes in
strong sulphuric acid, and then washing them. Perez4 subsequently
made some similar observations, noting also that normal partheno-
genetic development was commonest in those individuals which were
most robust.

Eichard Hertwig5 was the first to show that if the ova of
various Echinoderms are treated with certain reagents, and then
restored to normal sea-water, they will frequently display signs of
segmentation. The particular reagent originally employed by
Hertwig was a Ol per cent, solution of sulphate of strychnine. Not
long afterwards Mead c observed that the eggs of the marine Annelid,
Chaiopterm, which ordinarily become mature only after the entrance
of the spermatozoa, could be induced to throw out their polar bodies by
adding potassium chloride to the sea-water in which they were placed.

1 For chemistry of artificial parthenogenesis, see p. 313.

2 Janosik, "Die Atrophie der Follikel, etc.," Arch. f. Mikr. Anat., vol. xlviii.,
1896.

3 Tichouiiroff, "Die kiinstliche Parthenogenese bei Insekten," Arch. f. A not.
,i riii/x., Phys. Abth., Suppl., 1886.

4 Perez, " Des Effets des Actions mecaniques sur le Developpement des
(Kufa non-fecondes, etc.," Proces-Yerbaux de la Soc. des Sciences de Bordeaux,
1896-97.

r> Hertwig (R.), "Ueber Befruchtung und Conjugation," Verhftndl. der
Deutsch. Zool (feMtlw/i., 1892.

0 Mead, Lectures delivered at Wood's ffoll, Boston, 1898.

FERTILISATION 231

Morgan l found that an addition of sodium chloride to sea-water
containing ova of sea-urchins caused these to form astrospheres,
while, if the ova were afterwards transferred to ordinary sea- water,
they sometimes proceeded to segment. The latter process, however,
was not normal, since the ova that had been subjected to this
treatment became transformed into masses of minute granules, and,
instead of acquiring cilia and giving rise to embryonic individuals,
they underwent a process of disintegration.

To Loeb belongs the credit of having done more than any other
worker to elucidate the physico-chemical aspects of the phenomena
of fertilisation. Loeb was the first definitely to succeed in producing
plutei from the unfertilised eggs of the sea-urchin. His original
method was to expose the eggs for about two hours to sea-water in
which the degree of concentration had been raised by about forty or
fifty per cent. This effect could be produced by the addition of
sodium chloride, but it was found to be immaterial what particular
substance was employed to raise the concentration, so long as it was
one which did not act injuriously on the eggs. The ova were
afterwards restored to normal sea-water, when they began to
undergo segmentation and subsequently developed into normal
plutei.

Loeb was able to show, further, that the parthenogenetic develop-
ment of the ova in such cases was brought about by a loss of water.
Thus, when the concentration of the sea-water was less than forty
per cent., some of the ova of the sea-urchin Arlacia could be induced
to develop, even though they were allowed to remain in the
hypertonic solution. By adopting similar methods a like result
could be effected for the other species of sea-urchin, and also in the
case of the starfish Asterias forbesii ; but it was necessary, as a
general rule, to restore the ova to normal sea-water, as the
continuance of abnormal conditions, although it might not hinder
segmentation, usually arrested the further course of development.2

It was found, however, that osmotic fertilisation differed in
several respects from fertilisation by a spermato/oon. Firstly, the
ova fertilised by the former method began to segment without
developing a membrane such as is invariably formed in normal eggs
shortly after the entrance of the spermatozoa. Secondly, the rate of

1 Morgan, " The Action of Salt Solutions on the Unfertilised and Fertilised
Ova of Arbacia, etc.," Arch. f. Entwick.-Mech., vol. iii., 1896, and vol. viii., 1899.

2 Loeb (J.), "On the Nature of the Process of Fertilisation, etc." Amer. Jour,
of Pht/siol., vol. iii., 1899. "On the Artificial Production of Normal Larvge from
the Unfertilised Eggs of the Sea-Urchin (Arbacia)" Amer. Jour, of PhysioL,
Vol. iii., 1900. " On Artificial Parthenogenesis in Sea-Urchins," Science, vol. xi.,
1900. "Further Experiments on Artificial Parthenogenesis, etc.," Amer. Jour,
of Pkysiol., vol. iv., 1900. These papers are reprinted in Loeb's Studies in
(Jeneral Physiology, vol. ii., Chicago, 1905.

232 THE PHYSIOLOGY OF REPRODUCTION

development in the artificially fertilised eggs was considerably slower
than in the eggs fertilised by spermatozoa. Thirdly, the larvae
arising from osmotic parthenogenesis, as soon as they began to swim,
did so at the bottom of the dish in which they were placed, instead
of rising to the surface of the water like normal larvse. It was
found also that the percentage of eggs which could be induced to
develop by the osmotic process was invariably very much smaller
than the percentage of normally fertilised eggs which underwent
development. The consideration of these differences led Loeb to
conclude that the spermatozoon in normal fertilisation carried into
the ovum not one, but several substances or conditions, each of which
was responsible for a part only of the normal characteristics of the
process ; and that, in order to imitate successfully the action of
the sperm, it would be necessary to combine two or more artificial
methods.

When the eggs of Strongylocentrotus purpnratus were put into
50 cubic centimetres of sea-water to which 3 c.c. of a decinormal
solution of a fatty acid had been added, and were left in this water
for about a minute, and were then transferred to ordinary sea-water,
they were observed to form membranes. It was also noticed that
the eggs underwent internal changes characteristic of nuclear division,
but they were rarely seen to segment. Subsequently they began to
disintegrate, and after twenty-four hours were nearly all dead. If,
however, the ova, after they had formed a membrane, were deposited
in sea-water which had been rendered hypertonic by adding 15 c.c.
of sodium chloride solution of two and a half times the normal
concentration, to 100 c.c. of sea- water, all or nearly all the eggs could
be induced to develop. Furthermore, the rate of development was
practically the same as that of normally fertilised eggs, a large
percentage of the blastulae looked normal and rose to the surface of
the water, and the plutei which developed showed the usual degree
of vitality.

The brothers Hertwig 1 had previously discovered that sea-water
saturated with chloroform induced the unfertilised eggs of the sea-
urchin to develop membranes. Herbst2 more recently showed that
benzol, toluol, creosote, or oil of cloves produced a similar effect.
Loeb 3 found that amylene and various other hydrocarbons and acids
also called forth membrane formation, and that eggs which were
subjected to these methods could be made to segment by subsequent

1 Hertwig (O. and R.), Untersuchungen znr Morpholoqie und Phyiiologie der
Zelle, Jena, 1887.

2 Herbst, " Uber die kiinstliche Hervorragung von Dottermembranen, etc.,"
Did. Centralbl, vol. xiii., 1893.

3 Loeb, The Dynamics of Living Matter, New York, 1906. This work contains
further references. "On an Improved Method of Parthenogenesis," Univ. of
California Publications : Physiology, vol. ii., Berkeley, 1904.

FERTILISATION 233

treatment with liypertonio sea- water in the way described. The
substances which called forth membrane formation can be divided
into two groups, the first consisting of hydrocarbons and certain
substitute products, and the second being comprised of certain acids.
Loeb states also that the order in which the two agencies are employed
is of vital consequence, for if the eggs are subjected to the meinbrane-
forrning solution after being placed in the hypertonic sea-water
instead of before, they develop a membrane, but shortly afterwards
disintegrate. As a result of this series of experiments he concludes
that the process of membrane formation is an essential and not a
secondary phenomenon.1 He makes the further suggestion that
membrane formation is brought about by a kind of secretory process,
due to the squeezing out under pressure of a liquid substance from
the interior of the ovum 2 (cf. Jenkinson, p. 182, above). According to
this view the excretion of the fluid is the essential feature, while the
actual formation of the membrane is probably only a secondary
mechanical effect of the sudden secretion. -

In the case of the starfish it was found that the process of artificial
membrane formation was alone sufficient to induce parthenogenetic
development without any further treatment with hypertonic sea-water.
This observation is connected by Loeb with the fact that starfish
eggs are sometimes able to develop in the absence of any external
cause or agency. Parthenogenetic development of starfish eggs has
been produced also by mechanical agitation ; 3 but it is possible, as
Loeb observes, that the diffusion of carbonic dioxide, or some other
gas, into or from the eggs may be the real exciting cause.4

Loeb found also that the unfertilised eggs of the Annelid
Cha'topterux could be made to develop into swimming larv.t by
adding a small quantity of a soluble potassium salt to the sea-water
in which they were placed.5 The same result could be brought about
by the addition of hydrochloric acid. The eggs appeared to undergo
development, as far as the trochophore stage, but without segmenting.

Lillie'5 (F.),however, found that the nuclear divisions were abnormal,
and that the apparent trochophore larva? were not typical, being in
reality merely " ciliated structures " which were far behind the real

1 It was found, however, that in the case of the starfish a very small number
of eggs could develop without first forming a membrane, and that this
number could be increased by transitorily treating the eggs with acidulated
sea-water. See below.

2 Loeb, " Ueber die Natur der Losungen, etc.," Pjliigcr's Arch., vol. ciii., 1904.

3 Mathews, " Artificial Parthenogenesis produced by Mechanical Agitation,"
Amer. Jour, of Physiol., vol. vi., 1901.

4 Loeb, The Dynamics of Living Matter, New York, 1906.

•' Loeb, "Experiments on Artificial Parthenogenesis in Annelids, etc.," Amer.
Jour, of Physiol., vol. iv., 1901.

" Lillie, "Differentiation without Cleavage in the Egg of the Annelid
Ch(ttopterus pergamentaceus" Arch. f. EntwicK.-Meckanii, vol. siv., 1902.

8 A

234 THE PHYSIOLOGY OF REPRODUCTION

larva- in organisation. But Bullot1 showed that in another Annelid,
Ophelia, ova fertilised by hypertonic sea-water underwent a regular
segmentation.

Loeb has shown that the ova of limpets (Acmcw and Lottia) could
be artificially fertilised by the combined action of fatty acid and
hypertonic sea-water. This method also had the effect of hastening
maturation, since ova which could not be fertilised by spermatozoa
could be made to develop into larvte by the artificial treatment. It
was found, further, that maturation could be induced by the action
of alkaline sea-water, and that ova which were treated in this way
could be fertilised by spermatozoa or artificially fertilised.2

Bataillon 3 states that the unfertilised eggs of the lamprey, and
also those of the frog, can be made to undergo segmentation as far as
the morula stage by depositing them in a salt solution of such a
concentration that they lose water. Sugar solutions were also found
to be effective.4 The unfertilised eggs of the frog can be made to
segment also, and in many cases to develop into tadpoles and even
to undergo metamorphosis by puncturing them with a needle.5

Various experiments have been tried with the object of finding
out whether ova could be fertilised by substances artificially extracted
from spermatozoa, but so far without any positive result.6 Thus Gies
attempted to obtain an enzyme from spermatozoa, with a view to
seeing if such a substance would exert any influence on the unfertilised
ovum, but his experiments lent no support to the idea.7 Pizon's8
experiments on the same question were also negative in result.
(See p. 317.)

Loeb 9 has discussed at some length the question as to whether
any idea can be formed regarding the nature of the action of the
spermatozoon in causing the ovum to develop. He stated his belief
that the essential effect of the spermatozoon consists in the trans-
formation of part of the protoplasmic or reserve material in the egg
into the specific nuclein or chromatin substance of the nucleus. In

1 Bullot, "Artificial Parthenogenesis and Regular Segmentation in an
Annelid (Ophelia)" Arch. f. Entwick.-Mechanik, vol. xviii., 1904.

- Loeb, Univ. of California Publications : Physiology, Berkeley, vol. i., 1903,
and vol. iii., 1905.

3 Bataillon, "Nouveaux Essais de Parth6nogenese experiinentale chez lea
Vertebres inf6rieurs (Rana frisca et Petromyzon planeri)", Arch. f. Entirick.-
Mechanik, vol. xviii., 1904.

4 Loeb, loc. cit.

6 For an account of the experiments and further references see Loeb,
Artificial Parthenogenesis and Fertilisation, Chicago, 1913.

6 See Loeb, The Dynamics of Living Natter, New York, 1906.

7 Gies, " Do Spermatozoa contain Enzyme having the Power of causing
Development of Mature Ova ?" Amer. Jour, of PhysioL, vol. vi., 1901.

8 Pizon, " Eecherches sur une pretendue Ovulase des Spermatozoides,"
C. R. de VAcad. des Sciences, vol. cxli., 1905.

9 Loeb, loc. cit.'

FERTILISATION 235

each nuclear division one-half of the mass of each original chromo-
some goes into the nucleus of each of the two resulting cells. But
during the resting period which elapses until these nuclei are ready
to divide again, each chromosome grows to its original size, and then
a new division occurs. It is quite possible that the oxygen which is
required for the process of cell division is needed for the synthesis
of nuclein or chromatin substance. The fact that the rate of
development is influenced by temperature, in much the same way
as are chemical reactions, supports the idea given above that the
essential feature of fertilisation consists in the starting or the
acceleration of a chemical reaction which is going on steadily in the
egg. Loeb was disposed to conclude, therefore, that the spermatozoon
acts as a positive catalyser, but further evidence has led him to reject
this idea as improbable. He pointed out that, if it were correct,
normal sea-urchin eggs should segment if kept for a sufficiently long
period, and that it ought to be possible to induce segmentation by
applying heat, since heat is known to accelerate chemical reactions,
but neither of these results could be obtained.

He then suggested the possibility that the spermatozoon, in
conjugating with the ovum, removed from the latter a negative
catalyser or condition whose existence in the ovum somehow inhibits
the process of development. This suggestion seemed to provide an
explanation of the secretory phenomena, which, on Loeb's hypothesis,
are the cause of the membrane formation. "Finally, we may be
able to understand a fact which [has been] observed in the eggs of
a starfish, and which has not yet been mentioned, when the eggs
of Asierina or Asterias are allowed to ripen, they will die within a
few hours unless they develop either spontaneously or through the
influence of sperms or some of the above-mentioned agencies. The
disintegration which leads to the death of the non-developing egg is
obviously due to an oxidation, since I found that the same eggs
when kept in the absence of oxygen will not disintegrate. We
know that oxygen is an absolute prerequisite for the development
of the fertilised egg" [but this statement is disputed by Delage].
The fact that oxygen is a poison for the mature but non-developing
egg shows that the chemical processes which occur in the unfertilised,
non-developing egg must be altogether different from those which go
on in the developing egg of the starfish.1

1 Loeb, loc. cit. See also "The Toxicity of Atmospheric Oxygen for the
Eggs of the Sea-Urchin after the Process of Membrane Formation " ; " On
the Necessity of the Presence of Free Oxygen in the Hypertonic Sea-water
for the Production of Artificial Parthenogenesis " ; " On the Counteraction of
the Toxic Effect of Hypertonic Solutions upon the Fertilised and Unfertilised
Egg of the Sea-Urchin by lack of Oxygen," Univ. of California Publications :
Physiology, vol. iii., 1906. See also " Versuche iiber den Chemischen Charakter
des Befruchtungsvorgangs," Biochem. Zeitsch., vol. i., 1906. " Weitere Beobacht-

236 THE PHYSIOLOGY OF REPRODUCTION

Loeb's conclusion was that the phenomenon of fertilisation (as
studied in the sea-urchin, the starfish, Lottia, Poli/noe,a,nd Sipunculids)
consisted essentially, firstly, in a liquefaction or hydrolysis (or both)
of certain fatty compounds in the ovum, and secondly, in an initiation
in the right direction of a new process of oxidation.1 These changes
which occur in the fertilised egg lead to the synthesis of nuclein
material from the protoplasm. According to this view, the process
of astrosphere formation is not the direct effect of the act of
fertilisation, but is a secondary consequence of the new chemical
changes which are brought about by the entrance of the sperma-
tozoon.

In a later work Loeb - has elaborated his theory further. Mem-
brane formation is regarded as an essential factor in normal
fertilisation, and is of the nature of a cytolysis of the egg, for all
cytolytjc agents (e.g. foreign blood or cell extracts) produce it.
Normally the fertilisation membrane is brought about by a lysin
carried in by the sperm, which also carries another substance that
serves to counteract the evil effects of membrane formation (p. 194).

Delage,3 however, has adduced experimental evidence, some of

ungen iiber den Einfluss der Befruchtung und der Zahl der Zellkerne auf
die Saurebildung im Ei," Biochem. Zeitsch., vol. ii., 1906 ; " Uber die Super-
position von kiinstlichen Parthenogenese und Samenbefruchtung in demselben
Ei," Arch. f. Entivick.-Mechanik, vol. xxiii., 1907; "Uber die allgemeinen
Methoden der kiinstlichen Parthenogenese," Pflugeijs Arch., vol. cxviii., 1907 ;
and other papers in the same volume. The following papers also deal with
artificial parthenogenesis in various animals : Delage, C. R. de I' A cad. des
Sciences, vol. cxxxv., 1902 (describing fertilisation by anaesthetisation with
carbon dioxide during maturation) ; and C. R. de I'Acad. des Sciences, vol. cxli.,
1906 (describing fertilisation with various salt solutions); Treadwell, "Notes
on the Nature of Artificial Parthenogenesis in the Egg of Patella obsctirnj'
Biol. Bull., vol. iii., 1902; Scott, "Morphology of the Parthenogenetic
Development of Amphitrite" Jour, of Exper. Zool., vol. iii., 1906 ; Lefevre,
"Artificial Parthenogenesis in Thalassema mellita" Jour, of Exper. Zool.,
vol. iv., 1907 ; Kostanecki, " Zur Morphologic der kiinstlichen partheno-
genetischen Entwicklung bei Mactra" Arch. f. Mikr. Anat., vol. Ixxii., 1908.
.See also Mathews, whose paper has been already referred to (Chapter IV.,
p. 129, " A Contribution to the Chemistry of Cell Division, Maturation, and
Fertilisation," Amer. Jour, of Physiol., vol. xviii., 1907). This author lays stress
on the part played by the centriole, and suggests " that the various methods
employed to produce artificial parthenogenesis do not do so by their direct
physical action on the cell, but indirectly by producing in one way or another
active centriole substance in the cell cytoplasm, or by causing its discharge
from the nucleus." '

1 Loeb, "The Chemical Character of the Process of Fertilisation and its
bearing upon the Theory of Life Phenomena." — Address before the Inter-
national Congress of Zoologists, Boston, 1907, Univ. of California Publications,
vol. iii., 1907.

2 Loeb, Die chemische Enticicklungserregmig des tierischen Eies, Berlin, 1909 ;
Artificial Parthenogenesis and Fertilisation, Chicago, 1913 ; and Lillie, Problems
jif Fertilisation, Chicago, 1919. These important works contain full references.
For further discussion of the subject see p. 313 See also pp. 185 and 194.

3 Delage, "Les Vrais Facteurs de la Parthenogenese Experimentale,"
Arch, de Zool. Evper. et.G'en., vol. vii., 1908.

U<*», FERTILISATION 237

which is opposed to Loeb's interpretation of the observed phenomena.
This investigator has shown that it is possible artificially to fertilise
sea-urchins' eggs by treating them with solutions of tannin and
ammonia. He had already formed the conception that the essential
facts of cell division could be resolved into a succession of processes
involving coagulation and liquefaction. The formation of the
vitelline membrane is said to be essentially a coagulative process
(and also possibly the formation of the centrosome and of the nuclear
spindle), and the dissolution of the nuclear membrane and certain
of the accompanying events are regarded as evidence of liquefaction.
These considerations led Delage to employ tannin as an agent for
inducing coagulation, and ammonia for causing liquefaction. Tannate
of ammonia was found to produce a similar effect, but this is
explained by Delage 011 the assumption that, since tannin is a feeble
acid and ammonia is a feeble base, the ammonium tannate becomes
dissociated, so that the acid function (which brings about coagulation)
and the alkaline function (which causes liquefaction) may be supposed
to coexist in the solution, and so separately to exert an influence on
different parts of the egg. By adopting the above-described method,
Delage succeeded in artificially fertilising ova, so that they developed
into complete sea-urchins, but it is curious to note that the symmetry
of these individuals was liable to be abnormal, one of them being
hexameral instead of pentameral. Delage also obtained successful
results by using carbon dioxide and other agents, and starfishes' eggs
as well as sea-urchins' were successfully fertilised. Furthermore,
certain of the experiments seemed to indicate that the presence of
oxygen is not an important factor (as supposed by Loeb), since develop-
ment could be induced after the oxygen present had been very largely
eliminated (but see pp. 186-197).

It is, of course, obvious that Loeb's interpretation of the observed
phenomena of fertilisation among the Metazoa is inapplicable to the
process of gametic union in the Protozoa, in which the conjugating
units are often apparently similar and equipotential, and the same
objection may be offered to Delage's theory. It is possible, however,
that conjugation in the Protozoa, while presenting an essential
similarity to fertilisation in the Metazoa, initiates a series of chemical
processes of a relatively simpler kind. Moreover, the theory that
the changes consequent upon gametic union are the result of a
catalytic chemical reaction is in no way opposed to the vaguer
physiological conception that the object of the process is to secure
a rejuvenescence of vital substance without which the race cannot
. be perpetuated.

The cytological changes which occur in artificially fertilised ova
have been dealt with at considerable length by Wilson, to whose

238 THE PHYSIOLOGY OF REPRODUCTION

paper1 the reader is referred. It is shown that the ovum of the
sea-urchin, under an appropriate stimulus, is able to construct the
complete mechanism of mitotic cell division without the importation
of a sperm-centrosome, but beyond this a multitude of aberrations
are exhibited. The number of chromosomes is one-half that
occurring in normally fertilised eggs, being in the sea-urchin
eighteen instead of thirty-six. The centrosomes are primarily
formed de novo. According to Delage,2 however, the number of
chromosomes in artificially fertilised sea-urchins becomes eventually
restored to the normal by a process of auto-regulation.

1 Wilson (E. B.), " Experimental Studies in Cytology : I. A Cytological Study
of Artificial Parthenogenesis in Sea- Urchin Eggs," Arch. f. Entwick.-Mechanik,
vol. xii., 1901. For an account of the cytological phenomena in normal
parthenogenetic eggs, especially in insects, see Hewitt, "Cytological Aspects
of Parthenogenesis in Insects, " Memoirs and Proc. Manchester Literary and
Philosophical Soc., vol. 1., 1906.

2 ,Delage, " Etudes experimentales sur la Maturation Cytoplasmique chez
les Echinodermes," Arch, de Zool. Exper. et Gen., vol. ix., 1901. Cf. also
Tennent and Hogue, "Studies on the Development of the Starfish Egg,"
Jour, of Exp. Zool., vol. iii., 1906.

CHAPTER VII

THE ACCESSORY REPRODUCTIVE ORGANS OF THE
MALE AND THE MECHANISMS CONCERNED IN
INSEMINATION

" Mais, par ce moyen de propagation seminale, demeure es enfans ce qu'estoit
de perdu es parens et es nepveux ce que deperissoit es enfans, et ainsi
successivement." — RABELAIS.

A BRIEF description of the mammalian testis has already been given
in a chapter on the physiology of the spermatozoon (p. 159). It
remains, however, to state what is known regarding the functional
relations of the accessory male organs, and to refer incidentally to
the homologous structures in the female.

After traversing the tubules of the rete testis the spermatozoa,
swimming in the seminal fluid, make their way into the vasa efferentia,
which open into the canal of the epididymis. The vasa efferentia in
man are about twenty in number. Before passing into the epididymis
they become convoluted, forming the coni vasculosi. Both the vasa
efferentia and the tube of the epididymis contain smooth muscular
fibres in their walls. They are lined internally by columnar epithelial
cells provided with long cilia which assist the muscles in expelling
the semen.

Passing away from the epididymis, and in continuation with its
canal, is the vas deferens, which is nearly two feet long in the human
subject, and has an average diameter of about one-tenth of an inch.
It possesses a plain muscular wall, consisting of an outer layer of
longitudinal, a middle of circular, and an inner of longitudinal
muscles. On the inside of the muscles there is a mucous coat lined
by a columnar epithelium, which is not ciliated.1

A branch from one of the vesical arteries accompanies the vas
deferens, and eventually enters the testis, where it anastomoses
with the spermatic artery. The vas deferens, near its termination,

1 The epithelium of the vas in some animals (rat) is apparently ciliated.
Arising from the lower part of the epididymis, or from the vas deferens
close to its commencement, is a long narrow diverticulum which ends blindly.
This is the vas aberrans. It is probably a vestigial structure. A few small
convoluted tubes, situated near the head of the epididymis and representing
vestiges of part of the Wolffian body, are called the paradidymis or organ of
Giraldes. The innervation of the vas deferens is described below (p. 269).

. 239

240 THE PHYSIOLOGY OF REPRODUCTION

becomes sacculated, and in this region is known as the ampulla of
Henle. In the walls of the ampulla there are a number of small
tubular glands, which doubtless supply some portion of the ejected
fluid.

Disselhorst 1 believes that the ampulla acts as a seminal reservoir
(a function which has also been assigned to the vesicula? semiuales,
as described below), and states that he has found spermatozoa stored

FIG. 62. — Passage of convoluted seminiferous tubules (a) into straight tubules,
and of these into rete testis (c) (after Mihalkowicz, from Schafer) ;
6, fibrous stroma continued from mediastinum.

up in little pockets in the walls of this structure in animals during
the rutting time. He suggests, further, that there is a relation
between the state of development of the ampulla and the time occupied
by copulation. When the organ is small or absent, as in dogs, cats,
and boars, the coition is a slow' process, but when the ampulla is
large and well-developed, as in horses and sheep, the coitus occupies
a relatively short time.

The vas deferens on either side unites with the terminating

1 Disselhorst, " Ausfiihrapparat mid Anhangsdriisen der Mannlichen
Geschlechtsorgane," Oppel's Le/irbuck (far Vergleichenden Mikroscojrisehen,
Anatomic der WiiJteltiere, vol. iv., Jena, 19<>4.

THE ACCESSORY REPRODUCTIVE ORGANS 241

portion of the corresponding seminal vesicle to form the ejaculatory
duct. The two ejaculatory ducts, after traversing the prostate, open
into the floor -of the urethra by small slit-like apertures. Their
function is to convey to the urethra the fluid contained in the
seminal vesicles and in the vasa deferentia. The coats of the
ejaculatory ducts are relatively thin. The lining epithelium is
similar to that of the vas deferens.

The urethra, which serves as the common channel for both urine

fk *,"•*> - '" ' «r,

A I&ajt*

i^^P

^•:'^l^i.S!Li*

FIG. 63. — Transverse section through the tube of the epididymis.
(After Szymonowicz, from Schafer.)

a, Blood-vessel ; 6, circular muscle fibres ; <; epithelium.

and seminal fluid, is lined by a columnar epithelium resting oij a
vascular corium. The latter is surrounded by submucous tissue
containing two layers of muscular fibres, the inner being arranged
longitudinally,. a.nd -the outer circularly. The urethra in man is
usually described as consisting of three divisions, the prostatic, the
membranous, and the spongy portions. Of these the membranous
portion comprises that part of the urethra between the apex of the
prostate and the bulb of the corpus spongiosum, to be described
below. Opening medially into the prostatic portion of the urethra,
between the two ejaculatory ducts, is the aperture of the uterus
masculinus, or organ of Weber, which is the homologue of the vagina
and uterus in the female. This vesicle, which is a small cul-de-sac,

242 THE PHYSIOLOGY OF REPRODUCTION

and in man lies hidden by the prostate, is probably almost or quite
functionless, but it has a few very small glands which open into its
cavity. In some animals — such as the goat, for example — it is of
comparatively large dimensions, the upper part being divided into
two horns. In connection with it is a structure corresponding to the
hymen of the female. On the floor of the prostatic portion of the
urethra is an elevation of the mucous membrane and underlying
tissue, known as the crista urethra or caput gallinaginis. This

FIG. 64. — Transverse section through commencement of vas deferens.
(After Klein, from Schafer.)

a, Epithelium ; b, mucous membrane ; c, d, e, inner, middle, and outer
layers of muscular coat ; /, internal cremaster muscle ; #, blood-vessel.

eminence (which contains erectile tissue) serves when distended with
blood to prevent the semen from passing backwards to the bladder,
and mingling with the urine in the process of emission. It is
assisted in this function by the contraction of the sphincter of the
bladder.

The urethra in the female corresponds to that part of the male
urethra which is anterior to the openings of the ejaculatory ducts.
It is lined with a stratified scaly epithelium, like that of the vagina.1
Communicating with the female urethra are two complex tubular
glands known as the glands of Skene. Their ducts open very close
to the urethral aperture.

1 See footnote on p. 71 for interrelationships of female organs.

THE ACCESSORY REPRODUCTIVE ORGANS 243

THE VESICUL.%: SEMINALES

The seminal vesicles are offshoots from the lower ends of the vasa
deferentia. They consist in man of coiled tubes, about five inches
long, into which several diverticula sometimes open. The structure
of the vesicles is similar to that of the sacculated part of the vas
deferens, but the muscular layers are relatively thinner.

There has been some dispute as to the chief function of the
seminal vesicles. According to one view, they serve mainly as
receptacles for the spermatozoa before ejaculation. Most authorities,
however, are disposed to lay greatest stress upon their secretory
function.

Rehfisch 1 has shown that if fluids are injected into the testicular
end of the vas deferens, they first enter the seminal vesicle and
afterwards pass out through the urethra. He concludes that the
vesiculse serve the double purpose of secretory glands and reservoirs
for the semen.2 Misuraca3 states that in dogs and cats, which have
no seminal vesicles,4 the spermatozoa disappear from the male
passages from five to seven days after castration, whereas in guinea-
pigs, in which the vesicles are well developed, sperms may be found
alive as long as twenty days after the removal of the testes. This
is regarded as evidence that the seminal vesicles function as recep-
tacles for the spermatozoa. Moreover, Meckel 5 stated that he found
sperms in the vesiculie of the mole in the month of February (i.e.
during the breeding season) ; and Seubert 6 recorded a similar
observation about the hedgehog in August (also in the breeding
season) (cf. p. 55). Disselhorst,7 however, throws some doubt on
these observations. The present writer 8 has examined the contents
of the vesiculte of the hedgehog at all seasons of the year and has
failed to find spermatozoa even after the most careful search and
during the middle of the breeding season.

1 Eehfisch, "Neuere Untersuchungen iiber die Physiologic der Samenblasen,"
Deutsche med. Wochenschr., vol. xxii., 1896.

- It has been pointed out that the passage of spermatozoa into the vesicular
probably only occurs during the asphyxia of death in consequence of .the
constriction of the vas deferens which forces the contained fluid into these
organs (Luciani, Human Physiology, English Edition, vol. v., London, 1921).

3 Misuraca, "Sopra un importante questione relativa alia castrazione,"
Rivista sperimentale di Freniatria, vol. xv., 1890.

4 Seminal vesicles are absent not only in dogs and cats, but in many other
Carnivora, and also in Cetacea and Ruminantia. They are also wanting in
rabbits, but are present in the vast majority of Eodentia (Owen, Comparative
Anatomy, vol. iii., London, 1868).

5 Meckel, Beitrage zur Vergleichende A natomie : 1. Ueber die Manrdichen
eschl echtsteile des Maulwurfs, 1809.

6 Seubert, "Symbolum ad Erinacei europaei anatomen," Inaug. Dissert.,
Bonn, 1841.

7 Disselhorst, loc. cit.

8 Marshall, "The Male Generative Cycle in the Hedgehog," Jour, of Physiol.,
vol. xliii., 1911.

244 THE PHYSIOLOGY OF REPRODUCTION

That the vesicuhi* may undergo periodic enlargement in animals
which have a rutting season is an unquestionable fact. In the
hedgehog the increase in size is enormous. In the winter they are
hidden by the bladder and their weight may be only '1 gram. In
August the weight of the organs, together with their contained
secretion, was found to be 6 grams, and they occupied a consider-
able space in the body cavity. In April they were about one-fifth
their full size. In May they had reached their full size which
they retained until September or October, when they rapidly
diminished.

As evidence that the vesicuLe seminales are undoubtedly secretory
glands, Lode1 showed that in young animals, in which one of the
testes had been removed, the corresponding vesicula continued to
grow, and became filled with its characteristic fluid. It was evident,
therefore, that the fluid must have been secreted in the vesicula in
question, since it could not have been derived from the testis of the
other side. (The effects of complete castration on the growth and
activity of the vesiculse seminales are briefly referred to below.)
Stilling - and Akutsu 3 state that the epithelial cells of the vesiculte
seminales change their character according to whether they are in
a state of rest or activity. In the former condition they are larger
and contain more plasma substance. Kolster4 has described des-
quamation of epithelial cells in the selninal vesicles of the elk
(Cervits alces).

The secretion is formed apparently in considerable quantity.
Its character and composition vary somewhat in different Mammals.
In man it is gelatinous, and consists chiefly of globulins.5 It has
been investigated in Rodents by Sobotta,6 Rauther,7 and others,8
who describe it as a white or yellowish-white gelatinous fluid, which
becomes almost solid after ejaculation. . This capacity to clot is

1 Lode, " Experimentelle Beitrage zur Physiologic der Samenblasen,"
Sitziniysber. d. kais. Acad. d. Wisseitschaft in Wien, vol. civ., 1895.

2 Stilling, " Beobachtungen iiber die Functionen der Prostata und iiber
die Entstehungen prostatischer Concremente," Yin-how's Archiv, vol. xcviii.,
1884.

3 Akutsu, " Mikroscopische Untersuehung der Secretions'vorgange in den
Samenblasen," Pfluge^s Archie, vol. xcvi., 1903. Further references are given
in this paper.

4 Kolster, " Ueber einen eigenartigen Prozess in den Samenblasen von
Cermis alces," Arch.f. Mikr. Anat., vol. lx.. 1902.

5 Fiirbringer, " Die Storungen des Geschlechtsf unktion des Menschen,"
Nothnagel's Pathologic und Therapie, vol. xix., 1895.

6 Sobotta, "Die Befruchtung und Furchung des Eies der Maus," An-h. f.
Mikr. Anat., vol. xlv., 1895.

' Rauther, " Ueber den Genitalapparat einiger Nager und Insektivoren,
etc.," Jenaische Zcitsch. f. Xaturunssenschaft, vol. xxxvii., 1903.

8 De Bonis, " Sui Fenomenidi Secrezione nelle Cellule ghiandolari delle
Vescicule Seminale e delle Ghiandole di Cowper," Arch. Ital. di Anat. e di
Embryo!., vol. vii., 1908. Abstract in Arch. Ital. de BioL, vol. lii., 1909,

THE ACCESSORY REPRODUCTIVE ORGANS 245

supposed by Landwehr1 to be due to the presence of fibrinogen,
twenty- seven per cent, of which was found to be present. Calcium,
however, could not be discovered. Camus and Gley ~ state the
clotting is brought about by a specific ferment (which they call
vesiculase) in the prostatic secretion (see p. 248).

The clotting of the fluid, after its entrance into the female
passages in Rodents, prevents the escape of the spermatozoa and
so helps to ensure fertilisation. This fact was first discovered by
Lataste,3 who speaks of the " bouchon vaginal" formed by the
solidified secretion of the vesiculae. Similar observations have been
made by Leuckart 4 and others. The " bouchon vaginal " is said to
remain in situ for several hours, and then to become softened and
fall out.

The vesiculre of the hedgehog during the breeding season
contain a great quantity of yellowish-white fluid containing a
large number of irregularly shaped crystals resembling small ill-
formed crystals of edestin. Hopkins5 has examined chemically
the centrifugal precipitate obtained from the vesicular fluid, and
found it to consist mainly of a peculiar phospho-protein which
differed from most other phospho-proteins in its resistance to
solution in alkalis. He regards its existence in such large quantity
in a physiological secretion as a remarkable and exceptional
phenomenon which must presumably have some peculiar signi-
ficance. It has not been described as present in the vesicular
fluid of other Mammals.

Tarchanoff6 has suggested that in the frog the filling of the
seminal vesicles serves to excite sexual feeling in the male during
the breeding season. He states that the injection of milk, by
causing distension, excited sexual desire. But certain other obser-
vations have been made which seeni to disprove Tarchanoff's
conclusions (or at any rate to show that they are not universally
true). Thus, in some animals, it is known that sexual desire
exists before the seminal vesicles become full. Moreover, Steinach "
found that rats, whose seminal vesicles had been removed, still

1 Landwehr, " Ueber den Eiweisskorper (nbrinogene Substanz) der Vesicula
seminalis der Meerschweinchen," P finger's Archiv, vol. xxiii., 1880.

a Camus and Gley, " Note sur quelques faits relatifs a 1'enzynie prostatique
(vesiculase) et sur la fonction des glandes vesiculaires," C. It. de Soc. d<> Kiu!.,
vol. iv. (10th series), 1897.

3 Lataste, "Sur le bouchon vaginal des Rongeurs," Zool. Am., vol. vi., 1883.

4 Leuckart, Zur Morphologie mid Anatomie der (Jesehlec/itso/'ga/ie, Gottingen,
1847.

" Hopkins, Addendum to Marshall's paper1, loc. ait.

. 6 Tarchanoff, "Zur Physiologic des Geschlechtsapparates des Frosches,"
Pfliiger's Arckiv, vol. xl., 1887.

7 Steinach, " Untersuchungen zur Vergleichenden Physiologie der Mann-
lichen Geschlechtsorgane, etc.," Pftiiger's Arcfa'p, vol. Ivi., 1894.

246 THE PHYSIOLOGY OF REPRODUCTION

retained their desire for copulation although their fertility was
diminished.1

That the spermatozoa possess complete functional activity before
they can be in any way influenced by the secretion of seminal vesicles
has been conclusively shown by Iwanoff,2 who induced pregnancy
artificially in rabbits, guinea-pigs, and other animals, by injecting
into the female passages fluid obtained directly from the epididymis,
and mixed with a five per cent, solution of sodium carbonate. The
diminished fertility in Steinach's rats, after the removal of the
vesiculae, was probably due to the absence of formation of the
" bouchon vaginal," as has been suggested by Rauther.

It would seem probable that, in the majority of animals which
possess vesiculse seminales, the secretion of these glands serves to
dilute the semen, and so assists in providing a fluid medium for the
transference of the spermatozoa.

Exner3 has suggested that the seminal vesicles may have the
function of absorbing the seminal fluid which is not ejaculated, but
there is little evidence that this is the case.

Lode 4 found that in castrated bulls, horses, and guinea-pigs the
glandular epithelium of the vesicles atrophied, but the connective
tissue underwent hyperplasia. Gruber 5 and Pelikann 6 observed that
in castrated men the glands atrophied, but became filled with a kind
of mucous liquid.

Steinach7 has shown that in rats early castration inhibits the
development of the vesiculae. Further, castration in the hedgehog
done in winter prevents the seasonal growth of these glands in the
following spring. Unilateral castration, however, has no effect, the
vesiculse developing with normal symmetry.8 Vasectomy has also
no effect.

1 If both vesiculse and prostate were removed complete sterility resulted
(see below). See also Nussbaum, "Ueber den Bau und die Tatigkeit der
Driisen," Arch. f. Mikr. Anat., vol. Ixxx., 1912.

2 Iwanoff, "La Fonction des Vesicles seminales et la Glande prostatique,:>
Jour, de Phys. et de Path. Gen., vol. ii., 1900. See also papers in C. R. de la Soc.
de Biol., vols. Ixxiv. to Ixxx., 1913-17.

3 Exner, " Physiologic der Mannlichen Geschlechtsf unktionen," Frisch and
Zuckenhandl, Handbuch der Urologic, 1903.

4 Lode, loc. cit.

5 Gruber, " Untersuchung einiger Organe eines Castraten," Mailers Arrhiv.,
1847.

6 Pelikann, GerichtL-mediz. Unters. iiber d. Skopzentum in Russland, Giessen,
1876.

7 Steinach, " Untersuchung zur vergleichenden Physiologic der mannlichen
Geschlechtsorgane," Pflii get's- Arch., vol. Ivi., 1894. See also Zent. f.

vol. xxiv., 1910.

8 Marshall, loc. cit.

THE ACCESSORY REPRODUCTIVE ORGANS 247

THE PROSTATE GLAND

The prostate in man and other Mammals is a tubular gland
which surrounds the urethra at the base of the bladder, and opens
into it by a number of small ducts situated close to the apertures of
the ejaculatory ducts. It is usually described as consisting of three
lobes, two lateral and one median, the former comprising the chief
mass of the organ. Associated with the glandular substance is a
considerable quantity of plain muscular tissue. The prostate is
provided with lymph-vessels and blood-vessels. The arteries arise

FIG. 65. — Section through part of human prostate. (After Heitzmann,
from Schafer.)

C\ Concretions, often found in old subjects ; K, epithelium ;
J/, muscular tissue.

from the vesical, hsemorrhoidal, and pudic arteries. The veins
communicate with the dorsal vein of the penis and with the internal
iliac vein.1 The innervation of the gland is described below ' in
dealing with the mechanism of ejaculation (p. 268).

The prostatic secretion is a viscid, slightly acid liquid (sometimes
neutral or even alkaline), containing proteins and salts2 (see p. 301).
The characteristic smell of the ejected seminal fluid is said to be
partly due to the prostate secretion, which also contributes to the
formation of Bottcher's crystals described below (p. 299).

1 See Richardson, The Development and' Anatomy of the Prostate Gland,
London, 1904.

2 Poehl, Die Physiol.-chem. Grundlage der Spermintheorie, St. Petersburg.
1898 ; Furbringer, Die Storungen der GeschlechtsfunJction des Mamies, Wien,
1895 ; Berliner klin. Wochenschrift, vol. xxiii., 1886.

248 THE PHYSIOLOGY OF REPRODUCTION

De Bonis l describes the epithelial cells of the dog's prostate as
containing a small number of granules. When these have been
formed in sufficient quantity, so as almost to fill the cell, its wall
ruptures and the granules pass out into the lumen of the gland.
This occurs especially during coitus. After the discharge of the
granules fresh ones are formed in the cells of the gland.

Little is definitely known regarding the function of the prostate
beyond the fact that it contributes additional fluid to the semen.
It also appears to cleanse the urethra of urine prior to the
ejaculation of semen, since in a stallion (for example) the first fluid
to be expelled in sexual intercourse appears to be prostatic fluid and
contains no spermatozoa. It may, perhaps, assist in providing the
spermatozoa with nutriment.2 There is some evidence, however,
that it exercises a stimulating influence upon the .movements of the
spermatozoa.3 Steinach observed that prostatic fluid, when added to
normal saline solution, kept the spermatozoa in active movement for
a longer period than saline solution alone. Steinach also found that
rats in which the prostate gland, together with the seminal vesicles,
was extirpated, were absolutely sterile,4 but this may have been due to
failure to form a "bouchon vaginal" in the female. As already
mentioned (p. 245), the clotting which causes the formation of the
" bouchon " in Rodents is believed by Carnus and Gley 5 to be due to
a ferment (" vesiculase ") which is present in the prostatic fluid.6
The removal of the prostate in Steinach's experiments had no effect
in diminishing sexual desire.

Walker 7 has also adduced experimental evidence pointing to the
conclusion that the prostatic fluid of the dog stimulates the sperms
to more active movement.

Iwanoff8 also states that the secretion causes the spermatozoa to

1 De Bonis, "Uber die Sekretionserscheinungen in den Driisenzellen der
Prostate," Arch. f. Anat. u. Phys., Anat. Abth., 1907.

2 It has been suggested also that the prostate is a sphincter of the bladder,
but this is rendered unlikely by its absence in the female.

3 Fiirbringer, loc. cit. Kblliker, " Physiologische Studien liber die Samen-
fliissigkeit," Zeitsch. f. wiss. Zool., vol. vii., 1856.

4 Extirpation of the vesiculse seminales alone produced only partial sterility (see
p. 246). Walker (Johns Hopkins Hospital Reports, 191 1) obtained similar results.

r> Camus and Gley, loc. cit.

0 According to Walker the secretion which causes the clotting is produced
by a special gland which he calls the "coagulating gland" (Johns Ho/>/.-u/*
Hospital Bull., vol. xxi., 1910). See below, p. 300.

' Walker (G.), "Beitrag zur Kenntniss der Anatomie und Physiologic der
Prostate beim Hunde," Arch, f. Anat. u. Phys., Anat. Abth., 1899.

8 Iwanoff, " Ueber die nhysiologischen Rolle der accessorischen Geschlechts-
driisen, etc.," Arch. f. Mikr. Anat., vol. Ixxvii., 1911. See also Vichnersky
(Roussk Vratchi, vol. viii., 1909 ; abstract in Jour, de la Phys. et la Path. G<*u.\
who found that prostatic secretion obtained by merely squeezing the gland had
no effect on sperm movement, but that got by stimulation of nerves caused
energetic movement. The properties lasted three days in the cold, but were
less marked after boiling. See also Iwanoff, etc., C. R. Soc. BioL, vol. Ixxx.

THE ACCESSORY REPRODUCTIVE ORGANS 249

become active, but at the same time to shorten their life. Earlier
experiments by Iwanoff (see p. 246), however, show that spermatozoa
which have never come into contact with prostatic secretion possess
full functional activity, and are capable of fertilising ova successfully.1
Serralach and Pares 2 have adduced evidence indicating that the
prostate is an internally secreting gland which controls the testicular
functions, and regulates the process of ejaculation. It is stated that

FIG. 66. — Section through prostate gland of monkey.

«, Tubular alveolus lined with epithelium ; />, alveolus containing concretion
in lumen ; c, bundle of muscular fibres in connective tissue ; d, blood-
vessels in stroma.

if the prostate is removed spermatozoa are no longer produced in the
testis, and that the secretory activity of the accessory genital glands
ceases. These changes, however, can be prevented by the administra-
tion of glycerine extracts of prostate gland. The experiments were
upon dogs. The most obvious criticism of Serralach and Pares' view
is that it is unlikely, on phylogenetic grounds, that the functional

1 According to Herokawa (Biochcm. '/<>itxdt., vol. xix., 1909) the influence of
prostatic fluid on spermatozoa is due to its alkalinity. The addition of small
quantities of alkali to physiological salt solution was found to be favourable
to spermatozoa.

2 Serralach and Pai'es, " Quelques donnees sur la Physiologie de la Prostate
et du Testicule," C. R. de la Soc. Biol.t vol. Ixiii., 1908.

250 THE PHYSIOLOGY OF REPRODUCTION

activity of the essential organ of reproduction should depend on the
presence of an accessory gland of comparatively recent evolutionary
development. On the other hand, it is arguable that the prostate
may originally have formed part of the testis, and subsequently have
become differentiated as a separate organ in the course of phylogeny.
Reference may be made in this connection to the somewhat similar
theory, which certain gynaecologists have held, that the ovarian
functions are dependent on an internal secretion arising in the
uterus, whereas the most recent experimental evidence proves clearly
that this is not the case (see p. 376).

According to Lichtenstein l extirpation of the prostate has no
influence on the development of the secondary male characters or on
sexual desire (cf. Steinach, above).2

Griffiths3 has shown that the prostate glands in the hedgehog
and the mole undergo definite cyclical changes which are correlated
with changes in the functional activity of the testes (cf. p. 243). In
the quiescent state the prostate is composed of a few tubules lined by
small, flattened, epithelial cells, which are at this time incapable of
producing a secretion. With the approach of the breeding season
the tubules grow much larger and the epithelial cells become
columnar. During rut the prostate gland is a mass of tortuous
tubules, and has grown to eight to ten times the size of the quiescent
organ.4 The tubules are described as being filled with coagulated
mucus, containing a number of small round cells resembling leuco-
cytes ; while the epithelial cells are said to show numerous mucigenous
granules, especially in the inner or lumen half, but also, though less
markedly, in the outer half of each cell (cf. de Bonis' description of
the dog's prostate referred to above).5

The prostatic secretion is expelled into the urethra during the
sexual act by the contraction of the sheath of non-striped muscle
which surrounds each tubule throughout its entire length.

It has been shown in both man and animals that the growth of
the prostate is dependent upon the growth of the testes, since it
remains of small size until the time of puberty, when the generative
system reaches its full development. In those abnormal cases in

1 Lichtenstein, " Untersuchungen iiber die Funktion der Prostate," Zeitsch.
f. Urologie, vol. x., 1916.

2 But cf. Ott and Scott, p. 272 below, footnote at end of chapter.

3 Griffiths, "Observations on the Function of the Prostate Gland in Man
and the Lower Animals," Jour, of Anat. and Phys., vol. xxiv., 1890.

4 Marshall, loc. cit.

5 See also Griffiths, " Observations on the Anatomy of the Prostate," Jour,
of Anat. and Phys., vol. xxiii., 1889. For the comparative anatomy of the
prostate, see Oudemans' Die Accessorise/ten (jleschlechtsdrilsen der Saugethiere,
Haarlem, 1892. According to this authority, the hedgehog has two pairs of
prostates. The homologies of these glands in Insectivores still seem to be
obscure. See below, under Cowper's glands.

THE ACCESSORY REPRODUCTIVE ORGANS 251

which testicular growth is arrested, the prostate remains in a condition
of rudimentary development. Moreover, it has been shown that the
prostate in man normally undergoes atrophy in old age (see p. 718),
or as a result of castration, becoming transformed after a few years
into a mass of fibrous connective tissue containing a small number of
scattered muscle fibres in a state of degeneration. It has been found
also that the prostatic tubules disappear almost entirely in castrated
animals, and what is left of the epithelium completely loses its
secretory function1 (cf. p. 320). De Bonis' experiments, however,
seem to show that the administration of prostatic extract to castrated
dogs may lead to a renewal of activity and to the formation of fresh
granules in the secretory cells, biit this result could not be obtained
by employing testicular extract.

Castration in the hedgehog, done in winter, stops the periodic
enlargement of the prostate (just as with the vesiculae), while the
partial operation has no effect.2 Vasectomy also has no effect.

COWPER'S GLANDS

Cowper's glands are situated near the anterior end of the urethra.
They are a pair of small tubulo-racemose glands, and communicate
with the urethra by two ducts, apertures of which (in the human
subject) are about two inches below the openings of the vasa
deferentia. The lobules of the glands are surrounded by a firm
investing membrane which contains muscular tissue. They are lined
internally by a secretory epithelium.

The significance of the viscous secretion which these glands
produce is still unknown. It has been suggested that it serves to
cleanse the urethra of urine or semen ; also that it produces an
alkaline secretion which neutralises the acidity caused by the urine.
Since it is poured out in considerable quantity during coitus, and
appears sometimes to precede the ejaculation of the actual semen, it
is not impossible that the secretion of these glands may possess
the special function of ridding the urethra of all traces of urine
preparatory to the passage of the spermatozoa. The glands of Littre
or Morgagni, which beset the whole lining membrane of the urethra,
except near the external orifice, probably serve the same purpose as
Cowper's glands. (Cf. prostate, p. 248.)

1 Griffiths, loc. cit. Cf. also Griffiths, "The Condition of the Testes and
Prostate Gland in Eunuchoid Persons," Jour, of Anat. and Phy*., vol. xxviii.,
1893 ; Walker (G.), " Experimental Injection of Testicutar Fluid to prevent the
Atrophy of the Prostate Gland after the Removal of the Testes," Johns Hopkins
Hospital Bull., vol. xi., 1900 ; Wallace (Cuthbert), " Prostatic Enlargement,"
London, 1907 ; de Bonis, lor. cit.

- Marshall, lot-, cit.

252 THE PHYSIOLOGY OF REPRODUCTION

According to Nagel,1 Cowper's glands are of the normal dimensions
in castrated men, and consequently should not be regarded as purely
sexual organs. According to Barrington,2 removal of the glands in
rats and guinea-pigs has no effect on their breeding powers.3 On the
other hand, Schneidemiihl,4 whom Nagel quotes, says that in animals
they atrophy after castration. Griffiths5 describes these glands in
the hedgehog and the mole as undergoing periodic changes similar to
those of the prostate glands. In the hedgehog the secretion is
abundant during the summer (i.e. in the breeding season), and
possesses a disagreeable and penetrating odour. According to Gley,0
the secretion in this animal contains a ferment which causes the
fluid of the vesiculse seminales to clot, so that Cowper's glands in the
hedgehog may be the physiological equivalent of the prostate gland in
the Rodentia.7 Furthermore, Stilling 8 states that the epithelium of
Cowper's glands undergoes definite histological changes which depend
upon the occurrence of coitus.9

Corresponding to Cowper's glands in the male there are in the
female a pair of small glands situated one on each side of the vagina.-

1 Nagel, " Physiologie der Mannlichen Geschlechtsorgane," Pagers Handbuch
der Physiologie des Menschen, vol. ii., Braunschweig, 1906.

2 Barrington, " The Variations in the Mucin Content of the Bulbo-Urethral
Glands," Int. Monatsschr. fur Anat. itnd Phys., vol. xxx., 1913.

3 Double ovariotomy in adults reduces the size of the glands and inhibits
the secretion of mucin (Barrington).

4 Schneidemiihl, " Vergleichende Anatomische Untersuchungen iiber den
feineren Ban der Cowperschen Druse," Deutsche Zeitsch. f. Tiermedizin, vol. vi.,
1883.

5 Griffiths, "Observations on the Function of the Prostate Gland, etc.,"
Jour, of Aiiat. and Phys., vol. xxiv., 1890.

6 Gley, " Role des Glandes ge"nitales accessoires dans la Reproduction," Nel
primo Centenario dalla, ,1 forte di iMzzaro SpaUanzani A cad. 3d. e Stranieri, 1899.

7 It should be mentioned that very considerable doubt has been thrown
on the homology of what are often called Cowper's glands (those presumably
referred to by Gley and Griffiths) in the hedgehog with the glands known
by that name in other Mammals. According to Leydig (" Zur Anatomie. der
Mannlichen Geschlechtsorgane und Analdrusen der Saugethiere," Zeitxch. f.
wiss. Zool., vol. ii., 1850), Cowper's glands in the hedgehog are in reality repre-
sented by a pair of glands embedded in the urethral muscle (cf. Oudemans,
loc. cit.). The so-called Cowper's glands, which, as mentioned above, undergo
marked cyclical changes, are situated outside the pelvis close to the ischial
tuberosity and the base of the penis (Linton, " A Contribution to the Histology
of the so-called Cowper's Glands of the Hedgehog," Anat. Anz., vol. xxxi.,
1907). In the absence of embryological evidence, Linton appears to regard
these glands as siii generis. They are shown by this author to be composed
of two distinct kinds of secreting acini, one lined by a single layer of columnar
epithelial cells, and the other by many layers of polyhedral cells. Both kinds
secrete a considerable quantity of fluid, containing circular bodies which are
believed to be the nuclei of disintegrated cells, though no cells in process of
disintegration could be found in the single-layered type of acinus.

8 Stilling, "Tiber die Cowperschen Driisen," Virchmifs Arch., vol. c., 1885.

9 For an exhaustive account of the minute anatomy of the accessory glands
and ducts of the male reproductive system in the different groups of Vertebrata,
with full references to the literature, see Disselhorst in OppePs Lehrbvch,
loc. cit.

THE ACCESSORY REPRODUCTIVE ORGANS 253

These are the glands of Bartholini or Duverney. Their ducts open
out on to the vulva (between the hymen — posterior segment — and
labia minora). These glands secrete a viscid fluid which helps to
moisten and lubricate the surface of the vulva.

Harrington has shown that the secretory fibres to the glands in
the cat are contained in both the hypogastric and pelvic visceral
nerves, the former controlling the secretion of mucin. He believes
Cowper's glands to be innervated in the same way.

In addition to the accessory male glands described above, there
are, in many animals, other glands (perineal, inguinal, and preputial)
which are probably sexual, inasmuch as they are believed to serve as
means of attraction between the sexes during the breeding season.1
Most of these glands emit secretions of a musky odour, which in the
vast majority of cases is peculiar to the male, and very often to the
male during the rutting season only. Amongst the animals in which
this peculiarity occurs are the musk deer and other kinds of deer and
antelopes, the musk rat, the hamster, and many other Rodentia and
Insectivora. The temporal gland of the elephant is also stated to
emit a sexual secretion, especially in the male during rut.

THE COPULATOKY OKGAN

The penis is the intromittent organ of copulation. Besides
serving to conduct the urine to the exterior through the channel of
the urethra, it has the further function of conveying the-semen into
the genital passages of the female. This latter function is dependent
upon its power of erection under the influence of sexual excitement.

The erectile tissue of the penis is contained chiefly in three tracts,
the two corpora cavernosa, which are situated one on each side and
are united in the middle line, and the smaller corpus spongiosum,
which is placed inferiorly and surrounds the urethral passage. The
corpora cavernosa are .enclosed by an investment, containing plain
muscle fibres, numerous well-developed elastic fibres, as well as
bundles of white fibres. Trabeculse pass inwards from the fibrous
sheath and cross the cavities of the cavernous bodies, dividing them
into interstices which are filled with venous blood, being, in fact,
greatly enlarged vessels. The corpus spongiosum is similar in
structure, but its fibrous framework is not so well developed. The
canal of the urethra is surrounded by plain muscle fibres. Muscular
tissue is also present in the external coat of the spongy body, and in
the trabeculse.

1 Tiedemann, Comparative Vlujsiulogy, English Translation, London, 1834 ;
Gross, " Beitrage zur Anatomic der Geschlechtsdriisen der Insektivoren und
Nager," Arch. f. Mikr. A/iat.t vol. Ixvi., 1905. See also description of prepuce

(p. 254).

254 THE PHYSIOLOGY OF REPRODUCTION

At their proximal ends the three corpora are enlarged into bulbs.
Those of the cavernous bodies are covered by the ischio-cavernosi
muscles (or erectores penis), while the bulb of the spongy body is
surrounded by the bulbo-cavernosus muscle (or ejaculator urinse). At
its distal end the- corpus spongiosum becomes enlarged, forming the
glans penis, which is identical in structure with the rest of the body.

The integument of the penis in the region of the glans becomes
doubled in a loose fold. This is the prepuce or foreskin. Numerous
sebaceous glands are present near the free margin of the prepuce.
These glands emit an odoriferous secretion which in some animals is
especially marked during the season of rut.1

The penis is very sensitive to external stimulation, its surface
being beset with simple and compound end-bulbs and Pacinian
corpuscles, especially in the region of the glans.

The various kinds of end-organs in the external genital organs of
both sexes have been described at some length by Luciani,2 to whose
work the reader is referred. There are genital corpuscles, the nerve
fibres to which divide into five branches which end in knobs (Krause's
end-bulbs), as well as typical Meissner's corpuscles which are
capsulated and usually oval or elongated in shape, with a complex
and variable structure, and a series of transitional forms passing t
imperceptibly from Pacinian corpuscles to more elaborate structures.
The end-organs in the glans penis are not uniformly distributed, and
Head,3 taking advantage of this fact, was able to carry out an
interesting experiment illustrating sensory dissociation and the
inhibition of afferent impulses by other antagonistic impulses which
become dominant. It was found that the tip of the glans may be
devoid of heat-spots or end-organs responding to the sensation of heat,
but in possession of others which are sensitive to cold and pain. In
such a case " the end of the penis was dipped into a glass containing
water at 40° C. ; since no heat-spots were present and this temperature
has no effect upon the cold-spots, the only sensation evoked was a
peculiarly disagreeable pain. When, however, the temperature of
the water was raised to 45° C., pain was to a great extent displaced
by a vivid sensation of cold, due to stimulation of the cold-spots.
Instead of increasing the discomfort an elevation of temperature
ceased to be strictly painful because of the appearance of the specific
sensation of ' paradox cold.' But around the corona the penis is
always well furnished with heat-spots in addition to those for cold

1 Courant, " Uber die Praputialdriisen des Kaninchens und iiber Verander-
ungen derselben in der Brunstzeit," Arch. f. Mikr. Anat., vol. Ixii., 1903.

2 Luciani, Human Physiology, English Translation, edited by Holmes, vol. iv.,
London, 1917.

3 Head, " Release of Function in the Nervous System," Croonian Lecture,
Proc. Roy. Soc., B., vol. xcii., 1921. See also Head, with Rivers, Holmes,
Sherren, Thompson, and Riddoch, Studies in Neurology, London, 1920.

THE ACCESSORY REPRODUCTIVE ORGANS 255

and for pain ; as soon then as the water at 45° C. covered the corona
without reaching the foreskin, both cold and pain disappeared, giving
place to an exquisitely pleasant sensation of heat." " In none of
these cases was the process of selective inhibition in any way conscious.
The sensation evoked was a definite one of heat, of cold, or of pain,
but it was the final issue of a struggle between incompatible and
mutually antagonistic afferent impulses."

The arteries of the penis are the internal pudic arteries and the

T.A. ,

7.

Corp.

Spomj.

— Tt. Subf.

' A.

— T. A.

U.

FIG. 67. — Transverse section through adult human penis.
Eberth, from Nagel.)

x 3. (After

A., Artery ; C., cutis ; Com., communication between the two corpora
cavernosa ; Corp. 8pong., corpus spongiosum ; F., fascia ; Jr., nerves ;
S., septum ; T. J., tunica albuginea ; Te. Subc., tela subcutanea penis ;
Te. Subf., tela subfascialis ; Tun., tunica dartos penis ; Tr., trabeculte
of corpus cavernosum ; U., urethra ; V., veins.

dorsal artery. Some of the arterial branches project into 'the
intertrabecular spaces of the corpora cavernosa, and form coiled dilated
vessels which are known as the helicine arteries. In these arteries
the intima is folded, thus rendering them capable of great dilatation.
Moreover, these arteries present here and there a thickening of the
intiina in the form of little cushions which constitute a valvular
apparatus which limits the flow of blood into the corpora cavernosa,
when the muscular coat assumes the tonus that exists when the penis
is flaccid.1 In most cases the arteries are said to open into the venous
spaces, through the intervention of capillaries, but a few of the

1 Luciani, loc. cit.

256 THE PHYSIOLOGY OF REPRODUCTION

smaller arteries are stated to communicate directly with the cavernous
veins. The blood is carried away by two sets of veins, the one set
uniting to form the dorsal vein, and the other communicating with
the prostatic plexus and the pudendal veins.

When the venous spaces in the erectile tissue are distended with
blood the organ erects, becoming hard and rigid in condition. . It is
this power of erection which enables the penis to function as an
intromittent organ during copulation.

The above description applies more especially to the copulatory

FIG. 68. — Section through erectile tissue. (After Cadiat, from Schafer.)
a, Trabeculae ; b, venous spaces ; e, muscular fibres cut across.

organ in man. In the other groups of Mammals it has essentially
the same structure, but presents sundry modifications in the different
orders.1 In the Monotremata, however, there is no corpus
spongiosum.2 In some Mammals (Carnivora and Eodentia) the
penis is provided with a cartilaginous or bony support, the os penis,
which is developed especially in the region of the glans. It is

1 For an account of the structure of the copulatory organ in the various
groups of Vertebrates, with notes on the different modes of copulation and
bibliography, see Gerhardt, " Morphologische und biologische Studien iiber
die Kopulationsorgane der Saugethiere," Jenaische Zeitsch. f. Naturwissenschaft,
vol. xxxix., 1905.

2 The penis of the Monotreme is perforated by a canal, through which the
semen passes but not the urine. When in a relaxed state the organ lies in a
little pouch in the floor of the cloaca, from which it projects when erected.
The cloaca is the single common chamber through which the faeces and urine
pass to the exterior, as in birds and reptiles. In birds the penis is either
altogether absent or else is rudimentary (Crax, Crypturus, Lamellirostres,
Ratitae), Disselhorst, "Gewichts- und Volumszunahme der mannlichen Keim-
driisen, etc.," Zool. Anz., vol. xxxii., 1908.

THE ACCESSORY REPRODUCTIVE ORGANS 257

^— flf

FIG. 69. — Part of transverse section through penis of monkey.

a, Erectile tissue ; 6, urethra ; o, artery ; (/, nerve ; e. Pacinian body ;
/, fold of epithelium ; </, surface epithelium.

particularly large in the walrus. In the Cetacea the penis is often
of enormous size (six feet in length in some species), and terminates
in a point, but is otherwise normal. It can be withdrawn into the

9

258 THE PHYSIOLOGY OF REPRODUCTION

body when not being used. In copulation, whales apply their
ventral surfaces to one another.

In most Rodents and Marsupials the penis in the relaxed state is
withdrawn within an eversible fold of skin which constitutes a
dermal sac. When the penis is erected this sac is everted, and
forms its outer integument. Cole has described the structure of the
intromittent sac in the male guinea-pig, which appears to be typical
of many other Rodents.1 Dorsal to the urethral aperture when the
penis is withdrawn, and ventral to it when it is everted, is seen the
entrance to the intromittent sac. Lying in the cavity of the sac are
two horny styles. Two dorsal longitudinal folds are also noticeable.
These are the backward prolongations of the lateral lips of the
urethral aperture, the ventral lip consisting of corpus spongiosum
and separating the aperture of the urethra from that of the sac.
Attached to the base of the sac are two retractor organs which
consist of elastic fibres and erectile tissue, and are connected at their
other extremities with the integument of the penis. The eversion of
the sac is brought about by the erection of the two longitudinal folds
referred to above. The whole of the sac is composed largely of
erectile tissue, but the tissue of the longitudinal folds is even more
highly erectile than the rest of the sac. The entire structure is
provided with a very rich nerve supply. When the penis is erect,
and the sac everted, the two horny styles are protruded externally to
a considerable length. Moreover, both the sac and the surface of the
glans are covered with sharp spine-like structures, while in some
species of Caviidae they are provided also with two sharp horny saws
which are appended to the sides of the penis farther back. There
can be little doubt that the purpose of this unique contrivance is to
act as an exciting organ on the sexual structures of the female.

In another rodent, the marmot, according to Gilbert2 the skin
which covers the os penis becomes torn away during the rutting
season, so that the bone projects freely beyond the end of the glans
and is then used as a stimulating organ.

Structures which project from the penis, and are probably
employed as sexual irritants, are also found in the rhinoceros, the
tapir, and certain other animals.

In the cat the glans is beset with callous retroverted papillae,
which no doubt serve the same function. They are present also in
the lion and tiger, but are of smaller size.3

Perhaps the most curious modifications presented by the
mammalian organ of copulation are those found in certain species of

1 Cole, " On the Structure and Morphology of the Intromittent Sac of the
Male Guinea-Pig," Jour, of Anat. and Phys., vol. xxxii., 1898.

2 Gilbert, " Das Os priapi der Saugethiere," Morph. Jahrbuch, vol. xviii.

:) Owen, On the Anatomy of Vertebrates, vol. iii., London, 1868.

orpn. J
., Lond

THE ACCESSORY REPRODUCTIVE ORGANS 259

Ruminants. In the sheep, the gazelle, the giraffe, and a number
of antelopes, there is a long filiform process attached to the end of
the organ and traversed by the urethral passage. In some forms the
process arises medially (the penis being symmetrical) ; but in others,
such as the sheep, it is attached to the left side of the organ, the
distal end of which appears to have undergone some sort of torsion.1

FIG. 70. — Distal end of ram's penis, as seen from the left side, showing
glans and filiform appendage. The prepuce is folded back. Slightly
reduced.

The urethra opens to the exterior at the extreme end of the filiform
appendage. This structure — which has been investigated, especially
in the case of the sheep2 — is composed largely of erectile tissue

BI. v.

Muse.

Fibr. Cart.

Ep. Ur.

FIG. 71. — Transverse section through filiform appendage of ram, about
a quarter its length from the tip. x 45.

HI. V., Blood-vessels ; Ep. dr., epithelium surrounding urethral cavity ;
Fibr. Cart., fibro-cartilage ; Int., integument ; Muse., muscular layer ;
Ur., urethra.

which surrounds the urethra, and may be regarded as an extension
of the corpus spongiosum. Outside the erectile tissue is a well-
marked muscular layer which lies next to the integument. The
process is supported by a pair of fibro-cartilage bodies, placed one on
each side of the urethra and extending throughout the whole length
of the structure.

1 Garrod, " Notes on the Osteology and Visceral Anatomy of Ruminants,"
Proc. Zool. Soc., vol. xlv., 1877. For other orders see below, pp. 261 and 272.

- Nicolas, "Sur 1'Appareil Copulateur du Belier," Jour, de VAnat. et la
Phys., vol. xxiii., 1887. Marshall, "The Copulatory Organ in the Sheep,"
Anat. Am., vol. xx., 1901.

26o THE PHYSIOLOGY OF REPRODUCTION

The fact that the filiform prolongation is an erectile organ points
to the conclusion that its function is insertion into the os uteri
during copulation. An examination of the uterus in the sheep shows
that the os, when open, is fully large enough to admit of the entrance

01.

Fibr. Cart

Fibr. Cart.

FIG. 72. — Transverse section through the middle of the glans penis
of the ram. x 45.

Corp. Cav., Corpus cavernosum ; Fibr. Cart., fibro-cartilage ; Gl., erectile
tissue of glans ; Int., integument ; Ur.t urethra.

of the distal portion of the penis in the region of the glans. If the
extreme distal end does so enter, the filiform process must extend
into the cavity as far, or nearly as far, as the junction of the relatively
short corpus uteri with the two cornua. That the appendage
functions in the manner described seems additionally probable in
view of the fact, to which sheep-breeders attest, that if the process is

THE ACCESSORY REPRODUCTIVE ORGANS 261

cut off the ram is rendered barren. Professor Robert Wallace
informs me that it used to be a regular practice, for the protection of
ewes while being driven south from the Highlands of Scotland, to cut
off the filiform appendage from the rams to prevent them from
impregnating the ewes on the way, this method of inducing sterility
proving quite as effective as removal of the testicles.

In the bull, the musk ox, and some other Ruminants the filiform
process is vestigial. The end of the penis itself (the glans) is some-
what pointed in the bulb and it is believed that it is inserted into the
os uteri in copulation. It does not swell up to the same extent as
in the stallion, where the erected organ almost fills the vagina of
the mare and much friction takes place before ejaculation is com-
pleted. The urethral aperture is central in the horse, as in the boar.

In the dog the process of coition is very prolonged. This is due
to the contraction of a sphincter in the female which prevents the
withdrawal of the male organ until almost fully relaxed.1

FIG. 73. — Distal end of bull's penis as seen from left side, showing glans and
urethral papilla representing vestigial filiform appendage. The prepuce
is folded back. About two-thirds natural size.

The penis in the male mammal is represented in the female by
the diminutive clitoris. This organ, however, is not traversed "by the
urethra (at least in the majority of animals). On the other hand,
the corpora cavernosa and the glans are represented by homologous
structures. The clitoris, like the penis, contains very numerous sensory
nerve endings 2 and undergoes erection during sexual congress.

The relation between the clitoris and the urogenital canal is
closer in some Mammals than in others. In some species (e.g. the
capybara among the Rodents, and Tupaia among Insectivores) the
clitoris is of considerable size, and is grooved along its under surface
in relation to the upper wall of the urethra. In other animals (e.g.
Ai'vicola, Talpa, and Stenops) the groove on the under surface of the
elongated clitoris is converted by the coalescence of its margins into
a tube, which constitutes the urethral portion of the urogenital
canal. Further, in the female of the spotted hyena (If. crocuta), the

1 Prolonged retention has also been known to occur with the human subject.

2 Worthmann, " Beitrage zur Kenntniss der Nervenausbreitung in Clitoris
und Vagina," Arch. f. Mikr. Anat., vol. Ixviii.

262 THE PHYSIOLOGY OF REPRODUCTION

whole of the urogenital canal, beyond the apertures of the ducts of
Bartholini's glands, is prolonged forward to the extremity of the
clitoris and terminates in a similar manner to that of the urethra of
the male. In this animal, therefore, the vagina is completely absent,
the os uteri opening directly into the urogenital canal, which is
elongated and tubular in form as in the male. A somewhat similar
condition has been known to occur abnormally in the human female.1

THE MECHANISMS OF EKECTION, EJACULATION, AND KETKACTION

The erection of the penis is brought about mainly by the dilatation
of its blood-vessels. First of all the bulbous (proximal) part of the
organ increases in size, and then the swelling extends throughout
the cavernous bodies, and eventually to the glans. If the penis is
cut across when in a state of relaxation only a small quantity of
venous blood exudes from the wound ; but if the same operation is
performed during erection, the blood flow is enormously increased,
while simultaneously becoming bright and arterial in colour.2
Frangois-Franck 3 observed a corresponding rise in the -arterial and
venous tension. He found also that the organ in the process of
erection became very considerably swollen in size before the increase
in the blood pressure had extended to the veins. Loven4 showed
that the veins in the penis are traversed by five times as much
blood during erection as they are in a state of repose; The same
investigator found that, whereas the ordinary arterial pressure in
the penis is about half that of the carotid, during erection it rose
to three-fifths that of the carotid. The increase in the amount of
blood in the organ is accompanied by 'a rise of temperature.5

There can be no doubt that the erection of the penis is brought
about partly through the contraction of the ischio-cavernosus (or
erector penis) and bulbo-cavernosus muscles, certain of the fibres
of which pass over the efferent vessels, and so arrest the. outward
flow of blood.6 The result of this contraction is, that whereas the

1 Watson (M.), "The Homology of. the Sexual Organs, etc.," Jour, of Anat.
and Phys., vol. xiv., 1879. See also note on p. 272 for other orders.

2 Eckhard, " Untersuchungen tiber d. Erektion d. Penis beim Hunde,;!
Beitr. zur Anat. und Phys., vol. iii., Giessen, 1863.

3 Fran9ois-Franck, "Recherches sur Hnnervation Vaso-motrice du Penis,"
Arch, de Phys., 1895.

4 Loven, Berichte ilber die Verhandlungen der Konigl. Sacks. Gesell. zu Leipzig,
vol. viii., 1866. Nikolsky, "Ein Beitrag zur Physiologic der Nervi erigentes,"
Arch.f. Anat. u. Phys., Phys. Abth., 1879.

6 Retterer, Article on " Erection," in Richet's Dictionnaire de Physiologic,
vol. v., 1902.

0 De Graaf (Regner), De Virorum Organis Generationi Inservientibu*,
Geneva, 1785. Gunther, Untersuchungen und Erfahrungen aus dem Gebiete
der Anatomie, vol. i., Hanover, 1837. Kobelt, I)e PAppareil du Sens Genital
des Deu.v &exes, Strasbourg, 1851. For further references, see Retterer, loc. eft.

THE ACCESSORY REPRODUCTIVE ORGANS 263

blood can freely enter the dilated vascular spaces of the penis, its
exit is retarded, while this leads to a further distension of the vessels,
the venous outlets of which become still more compressed.

Although the muscular mechanism of the penis unquestionably
assists in the erection of that organ, it is equally clear that it is
incapable by itself of causing that phenomenon, since erection cannot
be induced by ligaturing the efferent veins. Moreover, the penis can
be made to erect in animals in which the muscular mechanism has
been paralysed by the injection of curari, but the erection in such
cases is incomplete.

It is stated also that the smooth or unstriated muscle fibres,
which are scattered throughout the trabecular framework of the
corpora, participate in the process of erection, but there has been
some disagreement as to the precise part they play. Kolliker1
suggested that their action is temporarily inhibited, and that the
relaxation of the trabeculae, which consequently follows, permits
the vascular spaces to distend. According to Valentin,2 these muscles
contract, and in so doing cause a dilatation of the walls of the vessels,
which thereby increase in volume. Langley and Anderson's observa-
tions, which support Kolliker's suggestion, are described below in
giving an account of the nervous mechanisms of erection and
retraction.

It is obvious, however, that in those cases in which the penis
remains erected for a considerable time a constant circulation must
be maintained through both the afferent and the efferent vessels of
the organ.

In some animals (dog, cat, horse, hedgehog), but not in the rabbit
or man, the penis possesses an accessory muscle. This is called the
retractor penis. It consists of a thin band of longitudinally arranged,
unstriated fibres, inserted at the attachment of the prepuce, and
continued backwards in the middle line over the ventral surface of
the corpus spongiosum to the bulbous part of the urethra, where it
divides into two halves which separate on either side of the anus.
Some of the fibres are continuous with a portion of the bulbo-
cavernosus of the same side, while others are connected with the
wall of the urethra. When it contracts it causes a marked dorsal
curvature of the penis.3

1 Kolliker, Verhandl. der Wiirzburger Phyx. Mvd. G'esell., vol. ii., 1851.

2 Valentin, Lchrbuch der Physiologic, vol. ii., 1844.

3 Langley and Anderson, "The Innervation of the Pelvic and Adjoining
Viscera : Part III. The External Generative Organs," Jour, of Physiol., vol. xix.,
1895. The retractor muscle is remarkable for its sensitiveness to changes of
temperature, and at the same time for being unusually tenacious of life. It
can be cut out of the body and preserved in blood-serum, in a cool place, for
days at a time, and afterwards, on wanning, will relax and undergo spontaneous
contractions. At a temperature of 40° C. it is quite placid ; but, on cooling

264 THE PHYSIOLOGY OF REPRODUCTION

Although the sexual orgasm is usually accompanied by a high
degree of mental excitement, it is essentially a reflex action, and
can take place when all connection with the brain is severed by
transaction of the spinal cord. The friction which is set up between
the male and female organs during coition causes a discharge of
motor impulses in both sexes, the uterus undergoing a series of
peristaltic contractions. Thus Heape l has described a sucking action
on the part of that organ in the rabbit, the os uteri dipping down
into the semen at the bottom of the vagina to be withdrawn again
in co-ordination with a rhythmical contraction by the uterine
muscles. At the same time the accessory sexual glands in the female
(Bartholini's glands, etc.) discharge a secretion which is added to
the semen.

It is generally believed that the centre for erection lies in the
lumbo-sacral region of the cord.2 Numerous experiments have been
recorded which prove conclusively that it is not situated in the
upper part of the cord or in the brain. Thus, Goltz 3 showed that
transection of the spinal cord above the lumbar region did not
destroy the reflex. Brachet4 also has recorded the occurrence of
ejaculation under a similar condition. According to Miiller,5 only
the lower part of the cord need be retained in order to preserve
the erection reflex, since this is still present after the complete
destruction of the cord in the whole of the lumbar and the upper
part of the sacral region. Miiller was able to induce erection in a
dog, which had undergone this operation, by rubbing the surface of
the penis.6

It is known, however, that erection (and even ejaculation) can
also be induced voluntarily by stimuli conveyed from the brain (i.e.

slightly, it will shorten, and not infrequently enter into a series of slow
rhythmic contractions. If cooled to 15° C. it will contract to about one-
quarter of its original length. (Sertoli, "Contribution a la Physiologic
Generale des Muscles lisses," Arch. Ital. de Biol., vol. iii., 1883 ; Gruenhagen,
"Das Thermotonometer," Pfliiger's Arch., vol. xxxiii., 1884. See also Fletchei',
"Preliminary Note on the Motor and Inhibitory Nerve Endings in Smooth
Muscle," Proc. Phys. Soc., Jour, of Phys., vol. xxii., 1898.)

1 Heape, "The Artificial Insemination of Mares," Veterinarian, 1898.

2 See Onuf, " Notes on the Arrangement and Function of the Cell Groups
in the Sacral Region of the Spinal Cord," Jour, of Nervous and Mental Diseases,
1899.

3 Goltz, "Ueber das Centrum der Erectionsnerven," Pji '.tiger's Arch., vol. vii.,
1873. See also Goltz and Freiisberg, " Ueber die Functionen des Lendenmai ks
des Hundes," Pfliiger's Arch., vol. viii., 1874.

4 Brachet, Itecherches e.rperime'ntales sur les Fonctions du Systeme Nerr<'n.r
(langlionaire, Paris, 1839.

5 Miiller, " Klinische und Experimentelle Studien iiber die Innervation der
Blase, etc.," Deutsche Zeitsch. f. Nervenheilk., vol. xxi., 1902.

6 Goltz (Function d. Nereencentr. d. Froschen, Berlin, 1869) found that in the
frog the centre on which the copulation-clasp depends lies in the upper segment
of the cord. Every part of the body of the female attracted the male, which
would even embrace the dead female (see also Luciani, loc. tit.).

THE ACCESSORY REPRODUCTIVE ORGANS 265

by sexual emotion). It is interesting to note, therefore, that Budge l
and Eckhard2 were able to cause the penis to erect by electrical
stimulation of the cervical cord, the pons, and the crura cerebri.
The same result was obtained by Pussep by exciting a definite
region in the cerebral cortex. In this case erection was followed by
ejaculation.3

It is stated also that hanging and decapitation in man are
sometimes followed by erection.4 According to Spina,5 who experi-
mented on the guinea-pig, section of the spinal cord, near the last
costo-vertebral articulation, is invariably succeeded by erection and
ejaculation.

There are certain facts which seem to show that the higher nerve
centres exercise an inhibitory influence over the sexual processes.
Thus, Retterer 6 states that it is easier to induce erection by external
irritation in a dog whose spinal cord has been cut through, than in
a normal animal.

Eckhard 7 was the first to show that the penis in the dog could
be induced to erect experimentally by the stimulation of certain
nerves which he called the nervi erigentes. These nerves, whicli
are truly vaso-dilator, were found in the dog to arise from the 1st
and 2nd sacral nerves, and in some cases from the 3rd sacral nerve
also. Gaskell8 showed that in the rabbit the erector fibres leave
the spinal cord by the anterior (and not by the posterior) roots of
the 2nd and 3rd sacral nerves. Morat 9 also found that in the dog
these fibres are contained only in the anterior roots of the 1st and
2nd sacral nerves.

The corresponding parts in the female are similarly innervated.
Thus, Langley 10 has described stimulation of the sacral nerves in the
vertebral canal of the rabbit as producing dilatation and flushing of
the vulva. These effects were most marked on exciting the 3rd

1 Budge, " Ueber das Centrum genitospinale des Nervus sympatheticus,"
Yin-how's Archiv, vol. xv., 1858.

- Eckhard, toe. cit.

3 Pussep, " Ueber die Gehirnzentreri der Penisekretion und des Samener-
gusses," Inaug.- Dissert., St. Petersburg, 1902. Abstract in Le Physiologists
llmse, vol. iii., 1904.

4 Gotz, " (Jber Erektion und Ejaculation bei Erhangten," Inaiig.-J)ixsert.,
Berlin, 1898.

5 Spina, " Experimented Beitrage zu der Lehre von der Erektion und
Ejaculation," Wiener Ned. Blatter, 1897.

0 Retterer, Article " Erection," in Richet's Dictionnaire de Ph>/siolo(jit>, vol. v.,
Paris, 1902.

7 Eckhard, loc. cit.

* Gaskell, "On the Structure, Distribution, and Function of the Nerves
which Innervate the Visceral and Vascular Systems," Jour, of Pht/siol., vol. vii.,
1886.

9 Morat, " Les Nerfs Vaso-dilatateurs et la Loi de Majendie," Arch, de Phi/*.,
1890.

10 Langley, "The Innervation of the Pelvic Viscera," Proc. Phys. 8oc., Jour,
of PhysioL, vol. xii., 1891.

266 THE PHYSIOLOGY OF REPRODUCTION

and 4th sacral nerves. The stimulation of the 1st and 2nd sacral
nerves, on the other hand, generally produced contraction and pallor.
Langley obtained similar results in experiments on the male rabbit,
the stimulation of the sacral nerves causing either protrusion and
flushing of the penis, or else retraction and pallor.

Nikolski l had previously stated that, on stimulating the anterior
ramus of the nervus erigens (or the ramus from the 1st sacral) in
the dog, he obtained a vaso-constrictor instead of a vaso-dilator effect,
thus differing from Eckhard and other investigators.

Sherrington2 found that in the male monkey excitation of the
2nd and 3rd sacral nerves produced moderate erection, and that of
the 1st sacral only slight erection. In the female monkey the effects
of stimulating the 3rd sacral were usually greater than in the case
of the 2nd, while the 1st sacral produced no certain effects. Similar
results were observed in experimenting on the cat, but in this animal
stimulation of the 1st sacral nerve appears to have had a more
marked effect.

Franc/ns-Franck 3 found that the anterior ramus from the 1st
sacral was capable of causing both vaso-constriction and vaso-
dilatation. This investigator noticed further that both effects could
be produced by stimulating the hypogastric nerves, but that the
vaso-dilator action was more pronounced.

Budge 4 also described erector action from the hypogastrics in the
rabbit. Langley and Anderson,5 however, were unable to confirm
this statement, but they found that the hypogastrics sometimes
contained constrictor fibres for the external generative organs.

They state that they could discover no satisfactory evidence of the
presence of vaso-dilator fibres in any of the upper or lumbar set of
nerves. It would appear, therefore, that the vaso-dilator function is
probably confined to the lower or sacral set of nerves.

Following Langley and Anderson's description, the fibres from the
sacral set of nerves may be divided into .two groups or classes, the
visceral and the somatic. Stimulation of the visceral fibres (which
run in the nervi erigentes) produces dilator effects on the vessels' of
the penis (and vulva), as already described. It also causes inhibition
of the unstriated muscles of the penis, the retractor muscle of the
penis (when present), and the unstriped muscles of the vulva (in the
female). The somatic sacral nerves send motor branches to the ischio-
cavernosus and bulbo-cavernosus muscles, as well as to the constrictor

1 Nikolski, loc. cit.

2 Sherrington, "Notes on the Arrangement of some Motor Fibres in the
Lumbo-Sacral Plexus," Jour, of Physiol., vol. xiii., 1892.

3 Fran9ois-Franck, loc. cit.

4 Budge, loc. dt.

5 Langley and Anderson, "The Innervation of the Pelvic and Adjoining
Viscera," Jour, of Phygiol., vol. xix., 1895.

THE ACCESSORY REPRODUCTIVE ORGANS 267

urethras or deeper muscular stratum of the perineum. In the female
they innervate the erector clitoridis, which represents the ischio-
cavernosus, and the sphincter vaginae, which embraces the lower end
of the vagina, and is the homologue of the bulbo-cavernosus. The
sacral nerves, as far as Langley and Anderson l were able to determine,
send no visceral fibres by their somatic branches.

The same investigators found that stimulation of the upper or
lumbar set of nerves produced strong contraction of the vessels of the
penis,2 as well as contraction of the retractor muscle, and of the other
unstriated muscles of the penis, prepuce, and scrotum (dog, cat, and
rabbit). The penis underwent marked retraction as a result of the
excitation. Stimulation of the 2nd lumbar nerves in the cat generally-
produced a slight but distinct action on the external generative organs.
The 3rd, 4th, and 5th lumbar nerves in many cases had a strong
action, but the 6th had no action. The 1st lumbar and 13th thoracic
were found to have a slight action. In the dog stimulation of the
5th lumbar nerve had no effect upon the generative organs, but
the 1st lumbar was observed to have a distinct action, and also the
13th and 12th thoracic. In the rabbit no effect was produced by
stimulating the 1st lumbar nerve. The 2nd lumbar had a slight
action occasionally, but the 3rd, 4th, and 5th lumbar nerves always
had an effect which was more or less pronounced.

The fibres from the lumbar nerves run in the white rami
conimunicantes to the sympathetic chain, where the}" take two routes.
(a) The majority of the fibres take the course of the pudic nerves
(nervi pudendi). They follow the sympathetic chain to the sacral
ganglia, from which fibres are given off, and these run in the grey
rauii communicantes to the sacral nerves. Their further course is by
way of the pudic nerves (i.e. in the somatic branches), none apparently
running in the nervi erigentes (i.e. to the visceral branches). (5) The
second of the courses taken by the lumbar nerve fibres is that by the
pelvic plexus. Only a relatively small number, however, take this
route. Most of them run in the hypogastric nerves, but a few may
join the plexus from the lower lumbar or upper sacral sympathetic
chain, or from the aortic plexus. Of these latter, some may join the
first root of the nervus erigens, and proceed with it to the pelvic
plexus.3

It has already been mentioned that the clitoris in the female, like
the penis, undergoes erection during coitus. The same is the case
with the other parts of the vulva which contain erectile tissue. The
friction which is set up between these structures and the glans of

1 Langley and Anderson, loc. fit.

2 Vaso-constrictor fibres for the penis were first found by Eckhard (loc. eft.)
in the nervus dorsalis penis.

3 Langley and Anderson, foe. cit.

268 THE' PHYSIOLOGY OF REPRODUCTION

the penis causes a reflex discharge of motor impulses in both the female
and the male. In the female the uterus undergoes a series of
peristaltic contractions, by means of which the semen is sucked into
its cavity (see p. 173). Moreover, Bartholini's glands show an increased
activity and pour out a viscid secretion. In the male, the sexual
impulses culminate in the emission of the semen. This is brought
about by a series of muscular contractions, which probably begin in
the walls of the vasa efferentia and pass to the canal of the epididymis.
and thence along the vas deferens on either side. The vesiculae
seminales contract simultaneously, expelling their contents into the
vasa, and the mixed fluid passes out through the ejaculatory ducts
into the prostatic portion of the urethra. The prostatic muscles also
contract, and probably assist in forcing the semen along the urethra,
while at the same time expelling the secretion of the prostate glands.
Entrance to the bladder is prevented by the erection of the crista
urethrse, assisted by the contraction of the sphincter of the bladder,
as already mentioned. The final discharge is brought about by
the rhythmical contractions of the bulbo-cavernosus and ischio-
cavernosus muscles, which have the effect of emptying the canal
from behind forwards, and so ejecting the semen, mixed with
the various glandular secretions, into the vaginal passage of the
female.

The iunervation of the muscles of the penis has already been
described.

The secretory cells of Cowper's glands receive branches from the
pudic nerves.

The prostate is innervated by fibres coming both from the nervi
erigentes and from the hypogastric nerves. The former are purely
motor, whereas the latter are both motor and secretory. Eckhard l
found that stimulation of the nervi erigentes in the dog caused the
expulsion of the prostatic secretion into the urethra. Loeb 2 obtained
contraction of the prostatic vesicles by excitation of the hypogastric
nerves. Mislawsky and Bormann 3 confirmed both these observa-
tions, and found also that stimulation of the hypogastrics, while
inducing the muscles to contract, at the same time promoted
secretory activity in the glandular cells, the secretion continuing
so long as the stimulation was kept up.4 Fogge also states that

1 Eckhard, loc, cit.

2 Loeb (M.), "Beitrage zur Bewegung des Samenleiters," Inaug.-Dissert.^
Giessen, 1866.

3 Mislawsky and Bormann, "Die Secretionsnerven der Prostata," Zentralbl.
/. Phys., vol. xii., 1898.

4 Timofeew has described end-bulbs in the prostate, testis, and other male
genital organs. Some of these are of a peculiar kind, and are in connection
with two nerve fibres ("Zur Kenntniss der Nervenendigungen in den
Mannlichen Geschlechtsorganen der Saiuger," Anat. Anz., vol. ix., 1894).

THE ACCESSORY REPRODUCTIVE ORGANS 269

lie found hypogastric stimulation to produce contraction of the
prostatic muscles.1

Akutsu z has shown that the vesicular seminales in the guinea-pig
receive fibres (motor as well as secretory) by the hypogastric nerves.
The fibres leave the spinal cord in the 2nd, 3rd, and 4th lumbar
nerves.

Budge 3 showed that it was possible to induce contraction of the
vasa deferentia by stimulating the spinal cord at the level of the
4th lumbar vertebra. He observed also that contraction could be
caused by stimulating one of the sympathetic ganglia, apparently
the inferior mesenteric.4

According to Remy,5 stimulation of a small ganglion situated on
the inferior vena cava at the level of the renal veins in the guinea-
pig produced a sudden ejaculation.

FIG. 74. — End-bulb in prostate. (After Timofeew, from Nagel.)
a, Thick medullated nerve fibre ; b, fine medullated nerve fibre.

Loeb G states that he was able to induce contraction of the vasa
deferentia by stimulating the hypogastric nerves.

Langley7 found that most of the efferent fibres for the vasa
deferentia traversed the sympathetic in the region of the 4th, 5th,
and 6th lumbar ganglia, so that presumably they chiefly arose from
the 3rd, 4th, and 5th lumbar nerves. Sherrington8 observed that
in the macaque monkey (Macacus rhesus) the 2nd and 3rd lumbar
nerves, and in the cat the 3rd and 4th lumbars, contained motor
fibres for the vasa deferentia. The fibres giving this result could

1 Fogge, "On the Innervation of the Urinary Passage in the Dog," Jour,
of Physiol., vol. xxviii., 1902.

2 Akutsu, " Beitrage zur Kenntniss der Innervation der Samenblase beim
Meerschweinchen," Pfliiger's Archiv, vol. xcvi., 1903.

3 Budge, loc. tit.

4 Langley and Anderson, loc. tit.

6 Remy, "Nerfs ejaculateurs," Jour, de VAnat. et de la Phys., vol. xxii., 1886.
6 Loeb, loc. tit.
1 Langley, loc. tit.
8 Sherrington, loc. tit.

270 THE PHYSIOLOGY OF REPRODUCTION

be found outside the spinal cord in the genito-crural nerve. The
contraction of the vasa was of a slow and peristaltic kind, and did
not cease immediately the stimulus was withdrawn.1

Langley and Anderson, as a result of an extensive series of
experiments, conclude that the internal generative organs of the
cat and rabbit are supplied by fibres running out by the anterior
roots of the 3rd, 4th, and 5th lumbar nerves, and sometimes also
the 2nd. These fibres pass through the sympathetic to the inferior
mesenteric ganglia, and continue their course by the hypogastric
nerves. Stimulation of these fibres in the cat and the rabbit
caused strong contraction of the whole musculature of the vasa
deferentia and uterus masculinus (which Langley and Anderson
regard as the physiological homologue of the vesiculse seminales in
these animals). The vas deferens in contracting was observed to
become from one to three centimetres shorter, so that there could
be no doubt that the longitudinal muscular coat took part in the
process. The contraction was strong enough to cause emission of
semen from the aperture of the penis. It would appear, therefore,
that ejaculation occurred without erection. In the dog, in which
the longitudinal muscle layer is not well developed, the contraction
of the vas deferens, on excitation of the upper lumbar nerves, was
not nearly so pronounced.

Langley and Anderson found that stimulation of the sacral nerves
had no effect on the internal generative organs. These are innervated
exclusively from the lumbar nerves, as above described.2

In view of the facts which have been related, it would appear
that ejaculation is a reflex act of some complexity involving more
than one centre in the spinal cord. The centre for the final expulsion
of the semen must be the same as that for erection, since the muscular
mechanisms concerned are to a large extent identical in each case. •
The centre presiding over the internal generative organs is apparently
in the lumbar spinal cord. As already mentioned, Brachet observed

1 There has been some disagreement as to whether the vas deferens under-
goes true peristaltic movement. According to Budge (loc. cit.) this does occur
in the rabbit and cat. Fick confirmed Budge for these animals (" Ueber das
Vas deferens," Mailer's Archiv, 1856), but found no peristalsis in the dog
(cf. Langley and Anderson for the dog). On the other hand, Loeb (loc. tit!)
could discern no peristaltic movement in the vas deferens of the rabbit, but
only a powerful contraction. Nagel, who has more recently investigated
the question, states that the vas deferens in the rabbit does not undergo a
true peristaltic movement, but a simple quick contraction which suffices for
the emptying the tube (" Contractilitat und Reizbarkeit des Samenleiters,"
Verhandl. d. Pkys. Gesell. zu Berlin; Arch. f. Anat. u. Phys., Phys. Abth.,
1905, Suppl. See also Nagel, Handbuch der Phys. des Menschen, vol. ii.,
Braunschweig, 1906).

2 Langley and Anderson, loc. cit. That stimulation of the fibres which
supply the vas deferens in rabbits causes expulsive movements, without giving
rise to erection, was shown by M. Loeb, loc. cit.

THE ACCESSORY REPRODUCTIVE ORGANS 271

ejaculation after all connection with the higher centres had been cut
off. The centripetal nerves for the ejaculatory reflex are the sensory
nerves of the penis, the stimulation of the glans being particularly
effective.1

Erection has been observed to occur in animals which were
castrated late in life, sexual desire in such cases being to some extent

v. D.

in.

IV.

FIG. 75. — Diagram illustrating innervation of internal genital organs of
male cat. (From Nagel.)

H., Hypogastric nerve ; Ur., ureter ; T7. />., vas deferens ; II., III., IV.7
branches arising from 2nd, 3rd, and 4th lumbar nerves.

retained. It has been shown, however, that erection cannot be
induced experimentally in animals which have been castrated prior to
puberty ; or, at any rate, that it is far more difficult to cause erection
in such animals. Thus, in three experiments carried out by the
writer, in conjunction with Professor Sutherland Simpson,2 it was

1 For further references to the literature of the nervous mechanism of
erection and ejaculation, see Bechterew, Die Funktionen der Nervencentra,
Weinberg's German Translation, vol. i., Jena, 1908.

2 Simpson and Marshall, " On the Effect of Stimulating the Nervi Erigentes
in Castrated Animals," (juar. Jour. Exper. Phys., vol. i., 1908.

2/2 THE PHYSIOLOGY OF REPRODUCTION

found impossible to induce erection by stimulating the nervi erigentes
in three cats which were castrated when about half grown and after-
wards allowed to reach their full size. It is possible, therefore,
that in such animals the muscular apparatus of the penis fails to
develop sufficiently to admit of erection occurring, but it would seem
unlikely that the nervous mechanism is impaired. If erection is
due mainly to an inhibition of the vaso-motors of the penis, as is
ordinarily supposed, there would seem to be no theoretical reason
why it should not be possible to bring about that process experi-
mentally in castrated animals. It is conceivable, therefore, that the
process of erection is after all a more complex phenomenon than is
generally believed, but our -experiments throw no further light on
the mechanism of that process.1

1 Ott and Scott (Contributions from Laboratory of Medico-Chirurgical College
of Philadelphia, 1912) state that injection of prostatic extract causes erection,
the length of the penis and the breadth of the bulb being considerably greater
than after injection of testicular, ovarian, parathyroid, or pituitary extracts.

[Note to p. 262. The reproductive organs of bats, and the evidence as to
their manner of copulation are described by Wood Jones (" The Genitalia of the
Cheiroptera," Jour, of Anat., vol. li., 1917). The process appears to occur while
the animals are suspended. (See also Wood Jones, Jour, of Anat., vol. li., for
genitalia of Tupaia.) Meek has given an account of the genital organs in the
Cetacea. In the porpoise (Phoccena communis) the penis consists of two portions,
proximal and terminal ; during erection the terminal part remains pliable and
takes on a corkscrew-like movement, the proximal part becoming hard and
rigid ("The Reproductive Organs of the Cetacea," Jour, of Anat., vol. Hi., 1918).]

CHAPTER VIII1
THE BIOCHEMISTRY OF THE SEXUAL ORGANS

" Nous sommes dans un de ces chateaux des legendes allemandes oil les
murs sont formes de milliers de fioles qui contiennent les ames des hommes
qui vont nattre. Nous sommes dans le sejour de la vie qui precede la vie."—
MAETERLINCK, La Vie des Abeilles.

THE FEMALE GENERATIVE ORGANS
Mammals

Ix Mammals very little is known concerning the chemistry of the
female generative organs. The difficulty experienced in obtaining
material has rendered impossible a chemical investigation of the ovum
itself. The fluid contained in the Graafian follicles of the cow is
stated to be of a serous nature. From the corpora lutea of the same
animal amorphous and crystalline pigments have been isolated, both
of which belong to the class of substances called lipochromes or
Interns.2 These pigments are also found in other sites, e.g. in adipose
tissue, in serum, in the retina, and in milk. Similar pigment
substances have been isolated from plants. In fact, the later work
of Escher 3 has shown that the crystalline pigment obtained from the
corpora lutea is a hydrocarbon of the formula C^H^ and is identical
with the pigment carotin 4 obtained from plants. The luteiris are not
related to blood pigment, and although hsematoidin may be found in
corpora lutea, especially when they are fresh, the existence of the
luteins appears to be quite independent of the presence of blood
pigments. The luteins contain carbon and hydrogen and have a
yellowish or reddish colour. Exposed to light they undergo oxidation.
They are soluble in alcohol, ether, and chloroform, and in that respect
resemble fats, from which they differ, however, in their resistance
towards alkalis. With strong nitric acid and sulphuric acid they

1 By William Cramer.

2 Piccolo and Lieben, " Studi nel corpo luteo della vacca," Giorn. 8c. Natur.
ed Econ., vol. ii., 1866. Kuhne and Ayres, "On the Stable Colours of the
Retina," Jour, of Physiol., vol. i., 1878.

3 Escher, " tlber den Farbstoff des Corpus luteum," Zeitsch. f. physiol. Ckem.,
vol. Ixxxiii., 1912.

4 Willstatter, chapter on "Chlorophyll" in Abderhalden's Biochemisches
Handlexikon, vol. vi., 1911.

273

274 THE PHYSIOLOGY OF REPRODUCTION

give a blue colour. Their solutions in alcohol, ether, or chloroform
are further characterised by the absorption-spectrum,1 which shows
two bands in the blue part of the spectrum (between the lines F and
G). The Interns are usually associated with the fatty substances, i.e.
true fats and lipoids, in their distribution. The corpus luteum is
rich in fatty substances deposited in the cells in the form of numerous
relatively large globules. The morphological appearance of the hitein
cells is therefore similar to that of the adrenal cortex and the glandular
adipose tissue. This similarity extends to the nature of the fatty
substances present. These are coriiposed partly of true fats and partly
of lipoids, among which cholesterin and its esters can be identified
most readily. Phosphatides (lecithin) and cerebrosides, either free or
in combination with sphingomyelin, are also present.

The estimations of Iscovesco2 and of Chauffard3 and his col-
laborators have given quantitative data from which the following
table has been calculate d for the sow : —

: .-.:--. .••'•• •

Ovaries.

Corpus Luteum.

Fresh.

Dried.

Fresh.

Dried.

Total lipoids

Per Cent.

17-3

Per Cent.
3-01

Per Cent.
32-3

Per Cent.
5-87

Cholesterin

1-22

0-35

6-32

1-15

The figures represent averages, and the individual estimations
show considerable variations, since the lipoid content of the corpus
luteum varies with its functional state. Chauffard and his
collaborators distinguish three stages in the evolution of the corpus
luteum for which they give the following average figures : —

Initial hsemorrhagic stage
Mature stage
Regressive stage Ji. ?

Cholesterin Content.
1 '99 per cent.
5-84 ''„
10-92

Observations on the phosphaticles of the corpus luteum of the sow
during pregnancy 4 indicate a diminution as pregnancy advances. In

1 Thudichum, " Uber das Lutein und die Spektren gelbgef arbter organischer
Substanzen," Centralblatt f. d. med. Wissenschaft^ vol. vii., 1869.

2 Iscovesco, " Les lipoides de 1'ovaire," Comptes rend. Soc. de Biol., vol. Ixxiii.,
1912.

3 Chautfard, Laroche et Grigaut, " Fonction cholesterinogenique du corps
jaune," Comptes reiid. Soc. de Biol., vol. Ixxii., 1912.

4 Corner, " Variations in the Amount of Phosphatides in the Corpus Luteum
of the Sow during Pregnancy," Jour. Biol, Chem., vol. xxix., 1917.

BIOCHEMISTRY OF THE SEXUAL ORGANS 275

the following table the figures for the P2^5 percentage of the alcohol -
soluble lipoicls have been calculated as lecithin : —

Stage of Pregnancy.

' . . . •

Length of
Embryo.

Lecithin Per-
centage in
Fresh Tissue.

Mm.

Per Cent.

Early pregnancy -
Middle pregnancy
Late pregnancy -

7-13
98-140
190-270

•71
•48
•44

From observations on the ovaries and corpora lutea of pregnant
and non-pregnant cows Rosenbloom l has obtained figures from which
the following table has been abstracted. The figures for cholesterin,
which can be estimated very accurately, are very similar to those
obtained by the French observers. The differences in the figures for
the phosphatide content can be attributed largely to different methods
of extraction and calculation.

Per Cent, in Dry
Tissue of

Ovary.

Corpus Luteum.

Non-
Pregnant.

Pregnant.

Non-
Pregnant.

Pregnant.

Early. Late.

Early, i Late.

Neutral fats
Phosphatides
Cholesterin -

Per Cent.
0-755
0-394
0-446

Per Cent. Per Cent.
0-60 0-63
0-348 0-363
0-40 0-437

Per Cent.
2-95
14-10
1-09

Per Cent. 1 Per Cent.
3-05 I 2-99
14-90 14-87
T09 1-17

The corpus luteum is therefore characterised by an abundance of
lipoids. The interstitial cells of the ovary contain globules of similar
mixtures of lipoids.

What specific functions these lipoids subserve in the sexual
organs is not known, although there is no lack of speculation on the
subject. From the morphological similarity of the cells of the corpus
luteum and those of the adrenal cortex, an identity of function for
the two organs has been postulated. But since the specific functions
of the cortex of the suprarenal gland are still obscure the suggestion
is more brilliant than helpful. The. cells of the corpus luteum
and of the adrenal cortex resemble each other as much as they
resemble the cells of glandular adipose tissue,2 which occurs scattered

1 Rosenbloom, "The Lipins of the Ovary and Corpus Luteum of the
Pregnant and Non-Pregnant Cow," Jour. Biol. Ckem., vol. xiii., 1912.

2 Cramer, " On Glandular Adipose Tissue, etc.," Brit. Jour. Exp. Patkol.,
vol. i., 1920, p. 184.

276 THE PHYSIOLOGY OF REPRODUCTION

in circumscribed masses throughout the body, and the cells of the so-
called hibernating gland. All these cells have the appearance of
glandular cells in which numerous lipoid globules are deposited. It
is very probable that these various groups of tissues are functionally
correlated in so far as the metabolism of cholesterin and the associated
lipoids is concerned, so that changes or disturbances in the cholesterin
metabolism will be reflected in these various tissues. But from this
to an identity of function is a far cry.

Observations concerning the chemistry of human ovaries have
been made chiefly in certain pathological conditions of these organs.
Various protein substances have been isolated from the fluid contents
of ovarian cysts. In the case of cysts due to a dilatation of the
Graafian follicles the contents were found to be identical with other
serous liquids. From cystic tumours of the ovaries, the contents of
which may be either watery or gelatinous, a number of protein
compounds have been isolated, which, on hydrolysis, all yield a
considerable quantity of a reducing substance — glucosamine — and
therefore belong to the group of glycoproteins. Hammarsten l
isolated a substance, called by him Pseudomucin, which did not
coagulate on heating and was not precipitated by acetic acid. On
hydrolysis it yielded thirty per cent, glucosamine. Pfannenstiel 2
isolated from ovarian colloid another mucoid substance, Pseudomucin
/?, a gelatinous mass which was insoluble in acetic acid and water, but
was dissolved by dilute alkali. These substances are formed by the
activity of the cells lining the cysts.3

Birds

Our knowledge of the chemistry of the ovum is derived almost
entirely from investigations on the hen's egg. The average weight
of an egg is 40-60 gm., half of this being the weight of the
white of the egg, while the yolk weighs 12-18 gm. and the shell
5-8 gm.

The egg - shell contains chiefly calcium 4 carbonate. During
development the egg-shell loses inorganic substances, especially
calcium, to the amount of 0'15 gm. This goes to the building up of the
structures of the developing embryo.5 In some species the shell is

1 Hammarsten, " Metalbumin und Paralbumin," Zeitsch. f. physiol. Ckem.,
vol. vi., 1882.

2 Pfannenstiel, "Uber die Pseudomucine der cystischen Ovariengeschwulste,"
Arch. f. Giptcekologie, vol. xxxviii.

3 For further details concerning the chemical pathology of the ovaries see
Wells' Chemical Pathology, 3rd Edition, 1918.

4 Vaughan, "Estimation of Lime in the Shell and in the Interior of the
Egg before and after Incubation," Jour, of Physiol., vol. i., 1878.

5 Tangl, "Untersuchungen iiber die Beteiligung der Eischale am Stoffwechsel
des Einhalts wahrend der Bebriitung," Pfliige)J8 Arch., vol. cxxi., 1908.

BIOCHEMISTRY OF THE SEXUAL ORGANS 277

coloured by pigments, which are probably allied to the bile
pigments.1 There are variations in the strength and thickness of the
shells of different eggs. Sometimes they are exceptionally thin and
soft. Riddle2 holds that there is a loose association between the
production of inadequate shells and the early death of the embryo
before hatching. Feeding with calcium does not prevent the
production of inadequate shells, so that lack of calcium cannot be
its cause.

The shell membrane consists of a substance belonging to the group
of the keratins. It is very rich in sulphur (about four per cent. S),
and, on hydrolysis, yields a relatively large amount of cystin (see
p. 288). It also loses weight during development. The loss consists
of organic substances and amounts to 0'2 gm.

The chief constituents of the white and the yolk .of the egg
are water, proteins, fats, and phosphorised fats, while carbohy-
drates as such are almost entirely absent. The white of the
egg contains on the average 0'47 per cent, dextrose, the yolk
0'14 per cent., while for the whole egg the average is 0'45 per cent.
dextrose.3

The proportion in which these constituents are present in the
white and in the yolk of the egg differs, as will be seen from
the following table giving the total composition of both these
parts. The figures for the yolk are taken mainly from Riddle's
estimations.4

White of Egg.

Yolk of Egg.

Per Cent.
Water - 85 to 88
Protein - - 13-0
Fat 0-3
Phosphorised fat, calculated as lecithin - trace
Cholesterin - - „
Reducing sugar 0'47
Inorganic salts - 0"7

Per Cent.
45-40
15-04
25-25
11-15
1-75
0-14
0-96

Another important difference in the composition of the white and
the yolk of the egg is to be found in the relative quantities of the

1 Krukenberg, "Farbstoffe der Vogeleierschalen," Verhandlnngnn d. Pl»/s.
Mi'tf. GeaeUschaft, Wiirzburg, vol. xvii., 1883.

2 Riddle, "Studies on the Physiology of Reproduction in Birds," Anwr.
Jour, of Pkysiol., vol. Ivii., 1921.

s Hepburn and St. John, "Dextrose content of the Hen's Egg," Pro<:
Amcr. Soc. Biol. Chemists, 1921, Jour. Biol. Ckem., vol. xlvi.

4 Riddle, "Studies on the Physiology of Reproduction in Birds," Anwr. Jour,
of Physiol., vol. xli., 1916. This paper contains a full bibliography.

278 THE PHYSIOLOGY OF REPRODUCTION

inorganic constituents as they are present in the dry residue,1 both as
inorganic salts and in organic combination.

100 parts of Dry Contain —

Residue of ' - KjO. Na.,0. CaO. MgO. Fe.2O.,- P00,. 01.
White of egg - 1'44 1'45 0'13 0'13 0:00 0~20 1'32

Yolk of egg - 0-27 0'17 0'38 0'06 0'024 1'90 0'35

It will be seen that the yolk is distinguished by the presence of
iron which is almost completely absent from the white, and by its
richness in phosphorus. Although the percentage of iron present in
the yolk is very small, it is nevertheless greater than in almost any
other animal or vegetable food-stuff.

As a rule the proportions in which the inorganic elements are
present are given in terms of percentages of the ash. Such a table.2
which perhaps brings out more clearly the difference between the
white and the yolk of the egg, may be given here : —

100 parts of the Contain —

Ash of - K,O. Na20. CaO. MgO. Fe2O,- PA- SiOa- CL
White of egg - 3M4 31 -67 2'78 2'79 057 4-?i 1'06 28-82

Yolk of egg - 9-29 5 -87 13-04 2-13 1-65 65-46 0'86 1-95

There are, of course, slight variations between different eggs in
the amount of mineral constituents present in the ash. It is possible
that there are such variations even in the eggs laid by one and the
same bird at different periods. Systematic investigations on this
point have been made only with reference to the iron. These
observations show that more iron is present in eggs laid in spring
than in eggs laid by the same bird in autumn, the amounts varying
from O0129 per cent. Fe2O3 to 0'0086 per cent. Fe2O3, the maximum
found being 0'0167 per cent. Fe203. (The percentage is calculated
for the dried yolk.) This fact probably explains the very exaggerated
statements which have been made concerning the production of eggs
rich in iron by keeping hens on a diet rich in iron. The careful
observations of Hartung 3 show that there is indeed a distinct effect
produced by such a diet, provided that it is given over a prolonged
period — two months or more. But the effect of such a diet is limited,
and does not go beyond the physiological maximum. The percentage
of iron present in eggs laid under these conditions remains fairly
constant, and is about equal to the maximum found under normal
conditions, namely 0'0165 per cent. Fe2O3, so that the seasonal
diminution which normally appears is prevented.

1 Bunge, "Der Kalk und Eisengehalt unserer Nahrung," Zeitsch. f. Biologic,
vol. xlv., 1904, p. 532.

2 Albu and Neuberg, Physiologic und Pathologic des Mineralsto/wechseh,
Berlin, 1906, p. 241.

3 Hartung, "Der Eisengehalt des Hiihnereies," Zeitsch. f. Biologic, vol. xliii.,
1902.

BIOCHEMISTRY OF THE SEXUAL ORGANS 279

The phosphoric acid constitutes more than half of the ash of the
yolk, and it is interesting to note that both the phosphorus and
the iron, which are destined to enter into the composition of some of
the most important constituents of the cell, such as nucleoproteins,
haemoglobin, lipoids, etc., are already present in organic combination.
The phosphorus is contained in the phosphorised fats, which constitute
about eleven per cent, of the yolk, and partly in the phosphoprotein
vitellin, which also contains iron.

The phosphorised fats are obtained by extracting the yolk, which
has previously been freed from water, with cold ether, and precipitating
the ethereal extracts with acetone. The precipitate contains the
phosphorised fats, while the acetone solution contains the cholesterin
which has been extracted together with the phosphorised fats. After
all the ether-soluble phosphorised fats have been removed by the
ether, further extraction with cold alcohol will remove other
phosphorised fats from the yolk.

The precipitate obtained from the ethereal extract by acetone has
often been called lecithin, the name given to the simplest and best-
known phosphorised fat. But the work of Erlandsen,1 and of
Thierfelder and Stern,2 has shown, what in the case of nervous tissue
had been recognised long ago by Gamgee and by Thtidichum, that there
are a number of phosphorised fats very similar to lecithin and very
difficult to separate from each other. These substances, accompanied
always by cholesterin, are widely distributed through the organic
world. In fact they are present in every cell, and in almost every
animal fluid. This fact alone is sufficient to indicate that the
phosphorised fats and cholesterin must fulfil an important function in
the life of the cell.

What this function is has not yet been clearly recognised. We
know that anaesthetics such as chloroform, and toxins such as snake-
venom, exert/ their action on the cell by virtue of the power of the
phosphorised fats to absorb these substances. Lecithin also absorbs
or adsorbs sugars, and the resulting sugar-containing adsorption
complex is soluble in ether, while pure sugars are not. Ethereal
solutions of lecithin take up with great avidity dyes, such as brilliant
green, methyl violet, which are soluble in water, but not in ether, and
the resulting lecithin dye complex has then the solubilities of a lipoid.3
Many inorganic salts and alkaloids such as quinine are also adsorbed

1 Erlandsen, " Untersuchungen iiber die lecithinartigen Substanzen des
Herzmuskels," Zeitsch. f. physiol. Chem., vol. li., 1908.

2 Thierfelder and Stern, "Uber die Phosphatide des Eigelbs," Zeitsch. f.
pkysiol. Chem., vol. liii., 1907. For detailed information see the review of
Levene, " Structure and Significance of the Phosphatids," in Physiological
Reviews, issued by the American Physiological Society, Baltimore, 1921.

3 Cruikshank, " The Adsorption of Dyes and Inorganic Salts by Solutions
of Lecithin," Jour, of Pathol., vol. xxiii., 1920, p. 230.

280 THE PHYSIOLOGY OF REPRODUCTION

by lecithin. Lecithin also absorbs oxygen very readily and becomes
oxidised even at room temperature. It has, therefore, many of the
properties which we associate with living protoplasm ; it may be said
to absorb food-stuffs and to assimilate them in the sense of altering
the properties of these food-stuffs ; it shows selective staining and
it absorbs oxygen. Some experiments of the writer,1 carried out in
1908, suggest that these phosphorised fats may act as oxygen-carriers,
and that they may thus fulfil an important function in cell-respiration.
A similar view has been put forward also on purely theoretical grounds
by Mansfeld.2

However that may be, there can be little doubt that in the egg,
which contains an exceptionally large amount of phosphorised fats,
these substances have to fulfil a different function. Phosphorus
enters into the composition of many cell constituents, for instance
the complex protein substances found in the nuclei of cells, . the
so-called nucleoproteins, so that the assimilation of phosphorus is an
important factor in the growth of an organism. In birds the yolk
of the egg fulfils a function similar to that of the milk in Mammals ;
both supply the offspring with the material necessary for its growth.
We thus find that both the yolk and the milk are not only rich in
phosphorus, but that most of the phosphorus is present in organic
combination, as casein and nuclein in the latter, and as vitellin and
phosphorised fats in the former.

It was held at one time that the organism could not synthesise
organic phosphorus compounds from inorganic phosphates. This has
been disproved by Gregersen,3 who showed that animals can maintain
themselves in phosphorus equilibrium when inorganic phosphates are
the only source of phosphorus, provided that protein is also given.
Similarly the eggs of ducks fed on a diet containing only inorganic
phosphates were found to have a normal lecithin value.4 It is
therefore not very obvious why both egg-yolk and milk should be
so rich in organic phosphorus compounds; it may lie merely to

1 Cramer, Unpublished observations. It was found that watery emulsions
of egg-lecithin absorbed much more oxygen than water alone or watery
solutions of proteins, and that such a lecithin-emulsion sometimes greatly
accelerated the oxidation of hydriodic acid by the oxygen of the air. The
results", obtained were, however, very variable. Thunberg (Skandin. Ar<-h. f.
Physio?., vol. xxiv., 1911) has since shown that the absorption of oxygen by
watery lecithin emulsion is greatly increased by the presence of minute traces
of iron (1 : 6,000,000).

2 Mansfeld, "Narkose und Sauerstoffmangel," Pfltiffer't Arc/i., vol. cxxix.,
1909.

3 Gregersen, " Untersuchungen iiber den Phosphorstoffwechsel," Zcifw/t. f.
physiol. Chfni., vol. Ixxi., 1911.

vol. xiii., 1912.

BIOCHEMISTRY OF THE SEXUAL ORGANS 281

lighten the work of synthesis laid upon the cells of the embryo. In
any case it is certain that the mother synthesises organic phosphorus
compounds for the offspring. In birds it has been shown 1 that the
blood of laying hens is much richer in phosphorised fats than that
of non-laying hens or of male birds. This indicates that these
substances are transported in the laying hen from their depots to the
egg, and this transport is associated with the disappearance of the
yellow colour from the body, especially the beak, legs, and anus,
the natural colour for the Leghorns and all American breeds. Thus,
birds with pale legs, beaks, and ani, are stated to have a high average
egg production and their blood is rich in fatty substances. The
converse is said to hold true for hens with distinctly yellow legs.

*/ */ o '

beaks, and parts surrounding the anus.2

The yellow pigmentation is due to a lutein \vhich is associated
with the fatty substances both of the adult fowl and of the yolk. It
was isolated in crystalline form by Willstiitter and Escher,3 had the
composition C40H.X02, and found to be closely allied to, if not identical
with, the plant pigment xanthophyll. It is slightly different from
the lutein of the mammalian ovum.

During incubation the vitellin disappears and the phosphorised
fats diminish, so that at the twentieth day their quantity is reduced
by one-half.4 It is, of course, clear that the formation of nucleo-
proteins cannot account for this enormous consumption of phos-
phorised fats. Some of these substances reappear in the embryo. A
proportion of them contributes to the formation of bones, which
contain a considerable amount of inorganic phosphates ; part
reappears in the foetal tissues as phosphorised fats, especially in
the nervous tissue, which is very rich in these substances. That
portion of the phosphorised fats which is transformed into inorganic
phosphates may at the same time fulfil another very important
function by the oxidation of the fat group in their molecule. It will
be shown below that the development of the embryo is intimately
associated with, and perhaps dependent upon, the transformation of
chemical energy into heat. This transformation is brought about by

1 Lawrence and Riddle, " Sexual Differences in the Fat and Phosphorus of
the Blood of Fowls," Amer. Jour, of P/iysiol., vol. xli., 1916.

2 Warner and Edmond, " Blood Fat in Domestic Fowls in Relation to Egg
Production," Jour. Biol. Ckem., vol. xxxi., 1917.

3 Willstatter and Escher, " Uber das Lutein des Hiihnereidotters," Zeitsch. f.
physiol. Chem., vol. Ixxvi., 1912.

4 Merconitzki, "Die quantitativen Veranderungen des Lecithins im
enstehenden Organismus," Russky Wratsch, 1907, quoted from Biochemisches
Centralblatt, vol. vi., 1907. Plimmer and Scott, "The Transformations in
the Phosphorus Compounds in the Hen's Egg during Development," Jour, of
Physiol., vol. xxxviii., 1909. Riddle, " Metabolism of the Yolk during Incuba-
tion," Amer. Jour, of Pht/siol., vol. xli., 1916 ; also Jonr. of Morphology, vol. xxii.,
1911.

282 THE PHYSIOLOGY OF REPRODUCTION

the oxidation of certain organic substances, which are different in the
different classes of Vertebrates. It will be shown also that in birds
the chemical energy is furnished by fats; and it is very probable that
the phosphorised fats furnish at the same time material for the
formation of the tissues of the embryo and fat as a source of chemical
energy.

It is interesting to note that a similar double function has been
assigned to glycogen in the case of the developing rabbit.1 Of the
cholesterin present in the fresh egg about one-third disappears during
incubation. The remainder reappears in the embryo.

The phosphorus which enters into the composition of nucleo-
protein is bound up therein in the form of phosphoric acid, combined
with purine bases and sugars (pentoses or hexoses) (see p. 307).
Neither nucleoprotein nor sugars are present in the fresh egg, and
purine bases are present only in very small amounts. The fact that
during development these substances rapidly increase in amount
indicates, therefore, that a synthesis, not only of nucleoprotein, but
also of some of its constituent groups from the reserve material
of the egg (proteins and phosphorised fats), takes place during
development.2 The purine bases found in the embryo are essentially
the same as those found in the adult organism.

Of the phosphorised fats of the yolk, lecithin is the simplest and
best-known representative. Like all fats, it is an ester, a compound
of glycerine and fatty acids, some saturated, as stearic and palmitic
acids, others unsaturated, as oleic acid. Like all fats, it is soluble in
alcohol and ether. With water it swells up and forms a colloidal
solution. It is distinguished by the presence in its molecule of
one molecule of phosphoric acid to which one molecule of an
organic nitrogenous base, choline, is attached. If boiled with
baryta water it is decomposed into glycerophosphoric acid, fatty
acids, and choline. Lecithin forms loose compounds with proteins,
the so-called lecithalbumins, of which vitellin is probably one.

Vitellin is an ill-defined compound between lecithin and a protein
substance which itself contains about one per cent, phosphorus. It
is insoluble in water, but soluble in dilute 'solutions of neutral salts,
behaving in that respect like a globulin. On peptic digestion a
pseudonuclein, rich in phosphorus, is formed from the protein part
of vitellin. This pseudonuclein contains also a relatively large

1 Lochhead and Cramer, "The Glycogenic Changes in the Placenta and
Foetus of the Pregnant Rabbit," Proc. Roy. Soc., Series B, vol. Ixxx., 1908.

2 Kossel, " Weitere Beitrage zur Chemie des Zellkernes," Zeitsch. f. Pliysiol.
('hem., vol. x., 1886. Mendel and Leavenworth, "Chemical Studies on Growth :
VI. Changes in the Purine- Pentose- and Cholesterol-Content of the Developing
Egg," Amer. Jour, of P/iysiol., vol. xxi., 1898. Fridericia, " Untersuchungen
iiber die Harnsaureproduktion und die Nucleoproteid neubildung beim Hiihner-
embryo," Skandin. Arch. f. Physiol., vol. xxvi., 1912.

BIOCHEMISTRY OF THE SEXUAL ORGANS 283

amount of iron in organic combination, and it is this substance
which is responsible for the presence of iron in the yolk of the egg.
According to Bunge,1 this substance plays an important part in the
formation of haemoglobin in the chick. It is the precursor of
haemoglobin, and has, therefore, been called by him hsematogen.
It contains 5'19 per cent. P and O29 per cent. Fe. Plimmer2 has
isolated from egg-yolk another protein, livetin, soluble in water and
containing O'l per cent, phosphorus.

Two different fats have been isolated from the yolk — the one
solid, rich in palmitic acid; the other fluid, containing equal parts
of palmitic and oleic acids. A small amount of stearic acid is also
present in' both fats. The composition of the fatty substances is
influenced by the food. According to Henriques and Hansen3 the
fat of the food passes into the yolk in the same kind of way as it
passes into the fat deposits of the adult organism. The observations
of M'Collum and his collaborators 4 have given the extraordinary result
that the lecithins of the egg-yolk do not possess a specific composi-
tion, but that they are variable in respect of the nature of the fatty
acid radicals which they contain, and that these can be made to vary
by varying the food.

The food has also an influence upon the colour of the yolk, which
is due to luteins. Feeding with grains produces a light yellow yolk,
a dark yellow yolk results if grass and herbs are given, while feeding
with worms leads to the production of an even darker reddish yolk.
What the changes are in the colouring matter of the yolk has not
yet been ascertained.5

During the development of the chick a considerable portion of
the fat disappears. In other words, a certain amount of chemical
energy, which in the fresh egg is present in the form of fat,
disappears. Liebermann6 has shown, for instance, that of 5'4 gm.
of fat present in a fresh egg only 2'7 gm. can be recovered
when the chick is hatched. The fate of the chemical energy which
has thus disappeared has been accounted for completely by the
observations of Bohr and Hasselbalch,7 which are the most exact

1 Bunge, " liber die Assimilation des Eisens," Zeitsch. f. physiol. Ckem., 1884,
vol. ix.

2 Aders Plimmer, "The Proteins of Egg-Yolk," Jour. Chem. Soc., 1908.

3 Henriques and Hansen, "Uber den Ubergang des Nahrungsfettes in das
Hiihnerei," Skandin. Arch. f. Physiol., vol. xiv., 1903.

4 M'Collum, Halpin, and Drescher, "Synthesis of Lecithin in the Hen,"
Jour. Biol. Chem., vol. xiii., 1912.

6 For the morphological distribution of the constituents of the yolk, see
Waldeyer, " Die Geschlechtszellen," in Hertwig's Handbuch der Entivicklungs-
l<;hre der Wirbeltiere, vol. i., Jena, 1903.

6 Liebermann, " Embryochemische Untersuchungen," Pflitger's Arch., vol.
xliii., 1888.

7 Bohr and Hasselbalch, " Uber die Warmeproduktion imd den Stoffwechsel
des Embryo," Skandin. Arch. f. Physiol., vol. xiv., 1903.

284 THE PHYSIOLOGY OF REPRODUCTION

and comprehensive investigations on the subject of the metabolism
of the embryo.

The developing egg takes in oxygen and gives oft' C02. Bohr and
Hasselbalch showed that the respiratory quotient of the developing
egg — that is, the ratio of the amount of CO., excreted to the amount
of O2 absorbed — is 071. Such a quotient indicates the oxidation of
fat. From the amount of C02 excreted during a given period it is
possible to calculate the amount of fat oxidised during that period.
Under ordinary conditions the oxidation of fat produces heat which
can be determined experimentally. By calculating from the amount
of fat oxidised during development the amount of heat which would
be generated under ordinary conditions, and by actually determining
at the same time the amount of heat given off by the developing egg,
Bohr and Hasselbalch found during a period of twelve days : —

The amount of heat calculated from the amount of fat oxidised - 12'11 Cals.
„ „ actually given off - . - 12-16 „

This remarkable agreement in so complicated an experiment—
which is a triumph of the experimental skill of the observers — shows
clearly that fat is the almost exclusive source of the chemical energy
which is used up during development. Another very important
conclusion can be drawn from these observations, namely, that all the
chemical energy which disappears during development reappears in
the form of heat; none is transformed in an unknown way into
energy of a different kind, or transferred to the developing embryo.

This observation, which is of fundamental importance in its bearing
on our conceptions of life and living matter, was confirmed by Tangl.
The converse was also experimentally tested by Rubner ] in the case
of yeast. When yeast-cells undergo autolysis no energy is liberated.
These experimentally established facts dispose in a final and
conclusive manner of all speculations concerning the existence of
unknown forms of energy in living cells.

The intensity of the metabolic changes which take place during
development, and which can be expressed by the amount of C02
excreted, is very great.2 Calculated for the same unit of weight of
the animal, it is as great in the embryo as it is in the adult animal,
and may even exceed it. This is the case not only in birds, but also
in Mammals. These changes are bound up with the development of
the embryo. Exposure to cold, which delays development, also
diminishes the excretion of carbonic acid.3 Experiments on the eggs

1 Rubner, "Die Umsetzungswarme bei der Alkoholgarung," Arch.f. Hygiene,
vol. xlix.

2 Bohr and Hasselbalch, "Uber die Kohlensaureproduktion des Hiihner-
embryos," Skandin. Arch. f. J'lt<isi<>l., vol. x., 1900.

3 Pembrey, " On. the Response of the Chick, before and after Hatching, to
Changes in External Temperature," Jovr. of PkysioL, vol. xxvii., 1 894.

BIOCHEMISTRY OF THE SEXUAL ORGANS 285

of cold-blooded animals1 show that those conditions which favour
development, such as high temperature, also lead to an increase in
the CO2 excretion. But the relation between oxygen consumption
and development is not a simple one. For as J. Loeb has shown
in the parthenogenetic development of unfertilised eggs the oxygen
consumption increases before the actual development begins. And
Warburg 2 found that one can prevent the segmentation of the egg
without diminishing the respiration.

The problem of the energy exchange during development has
been attacked in a different way by Tangl.3 He determined, by
means of a calorimeter, the heat produced by the combustion of eggs
at different stages of their development. There is a gradual diminu-
tion of the caloric value as development goes on, indicating that
chemical energy is used up in the process of development. For the
chick the following " balance-sheet " can be drawn up from the
observations of Tangl and his collaborators. The caloric value of an
egg of average weight (54 gm.) is 87 Cals. The difference between
the caloric value of the fresh egg and that of the incubated egg is
23 Cals. These 23 Cals. represent the chemical energy which has
been used up for what Tangl calls the "work of development."
Calculated for 1 gm. of chick this amounts to 805 small calories.

Before Incubation. After Incubation.

Caloric value of egg - 87 Cals.

Total - - 87 Cals.

Transformed into heat - 23 Cals.
Present in body of developed

chick - - - - 38 „
Remaining unused - - 26 „

Total - - 87 Cals.

But since Bohr's work has shown that the chemical energy which
disappears during development is completely transformed into heat,
it would be better to replace the term " work of development " by the
term " energy of development."

The nature of the substances which by their oxidation furnish the
" energy of development " is different in the different classes of
animals. In birds it is furnished, as we have seen, by the oxidation
of fats, and possibly also of the fatty group of the phosphorised fats.
In Mammals, in which development proceeds in utero and there is a
constant exchange of material between the mother and the fostus, the
investigation of these problems is more difficult, o\ving to the
complexity of the conditions. Investigations on the respiratory

1 Bohr, " tiber den respiratorischen Stoffwechsel beim Embryo kaltbliitiger
Tiere," Skandin. Arch. f. Pkysiol., vol. xv., 1904.

2 Warburg, " Untersuchungen iiber die Oxydationsprocesse in Zellen,"
Miinchener Mediz. Wockensckr., 1912, p. 2550.

3 Tangl, " Beitrage zur Energetik der Ontogenese : I. Die Entwicklungs-
arbeit im Vogelei," Pfliiger's Arch., vol. xciii., 1903 ; vol. cxxi., 1908.

286 THE PHYSIOLOGY OF REPRODUCTION

quotient of the embryo in pregnant guinea-pigs and rabbits l indicate
that there is an oxidation of carbohydrate material, and Systematic
chemical investigations of the placenta and fetus of pregnant
rabbits '2 have shown that there is a constant and regular disappear-
ance of glycogen from the placenta, which reappears only partly as
such in the embryonic tissues. It can, therefore, be concluded that in
these animals glycogen furnishes at least part of the "energy of
development." But it is doubtful whether this conclusion can be
applied to all the Mammals, since in the case of the cow and of the
sheep very little glycogen is found in the placenta.

In reptiles 3 also the chemical energy used up during development
is furnished mainly by carbohydrates.

Similar observations have been made on the eggs of fishes,4 where
the energy of development was found to be very small.

In all these cases the chemical energy used up in the process of
development has been found to be furnished either by fats or by
carbohydrates. No conclusive evidence has as yet been obtained
that the store of nitrogenous substances' is used for energetic
purposes. Nor is it at all clear what changes the protein substances
of the egg undergo during development.6

Liebermann records a loss of nitrogenous substances in his analysis
of hens' eggs at various stages of development ; but as Hasselbalch 6
pointed out, this loss is accounted for by the egg-membrane, which is
left behind when the chick is hatched, and which was not included in
Liebermann's analysis.

Reference has already been made to the nitrogenous constituents
of the yolk ; the two phosphoproteins vitellin and livetin. The other
protein substances of the white of the egg can be distinguished
according to their reactions as albumens, globulins, and a substance
behaving like a peptone in so far as it is not coagulated by heat and
not precipitated by ammonium sulphate or by hydrochloric and acetic
acids. According to the investigations of Morner,7 this substance is

1 Bohr, " Der respiratorische Stoft wechsel des Saugethierembryos," Skandin.
Arch.f. Physiol, vol. x., 1900.

2 Lochhead and Cramer, "The Glycogenic Changes in the Placenta and
Foetus of the Pregnant Rabbit," Proc. Roy. Soc., Series B., vol. Ixxx., 1908,
p. 263.

3 Bohr, " liber den respiratorischen Stoffwechsel beim Embryo kaltbliitiger
Tiere," loc. cit.

4 Tangl and Farkas, " Beitrage zur Kenntniss der Ontogenese : IV. Uber
den Stoff u. Energieumsatz ini bebriiteten Forellenei," Pflilgei)s Arch., vol. civ.,
1904.

5 Emrys-Roberts, " A Further Note on the Nutrition of the Early Embryo
with special reference to the Chick," Proc. Roy. Soc., B., vol. Ixxx., 1908.

6 Hasselbalch, "Uber den respiratorischen Stoffwechsel des Hiihnerembryos,"
Skandin. Arch.f. Physiol., vol. x., 1900.

7 Morner " Uber die im Huhnereiweiss in reichlicher Menge vorkonimende
Mucinsubstanz," Zeitsch. f. physioL Chem., vol. xviii.

BIOCHEMISTRY OF THE SEXUAL ORGANS 287

a true glucoprotein and belongs to the mucoid substances. It has,
therefore, received the name Ovomucoid. On boiling with hydrochloric
acid it yields 34 per cent, of glucosamine.1 The ovomucoid present in
the white of the egg amounts to about 10 per cent, of the proteins;
6 per cent, of the proteins belong to the globulin group, the remainder
being the albumens. All the proteins of the white of the egg, not
only the ovomucoid, are exceptionally rich in the carbohydrate radical,
and on boiling with dilute hydrochloric acid yield considerable
quantities of glucosamine. The albumens and globulins contain about
10 per cent, of glucosamine. This explains perhaps the almost
complete absence of carbohydrates in the egg. There is the
further significant fact that the developing tissues of the embryo
are very rich in mucin, a protein containing considerable quantities
of glucosamine.

The globulin fraction of the egg-white has not yet been studied
in detail. It is probable that it is a mixture of several globulins.

The investigation of the albumen fraction has been greatly
facilitated by the work of Hofmeister z and of Hopkins,3 which has
made it possible to obtain part of the albumen fraction in a crystallised
form. In this way Osborne and Campbell 4 have isolated two different
albumens, the crystallisable " ovalbumeii " and the non-crystallisable
" conalbumen." Possibly even these two substances are mixtures of
albumens, for Bondzinski and Zoja5 claim to have isolated from the
crystallisable ovalbumeii several albumens by means of fractionate
crystallisation. Crystalline egg albumen contains 0'13 per cent.
phosphorus,6 and is therefore another source of phosphorus in organic
combination.

The white of the eggs of some Insessores has the peculiar property
of forming a transparent fluorescent jelly when it is coagulated by
heat.7 The name " Tata-eggwhite " has been given to this substance.
This phenomenon is probably due to the presence of a relatively" large
amount of basic salts in the white of the egg, since the white of a
hen's egg will also coagulate to a' transparent jelly if the egg has been
kept for a few days in ten per cent, caustic potash.

1 Quoted from Ergebnisse der Physiologic, vol. i., Part I.

2 Hofmeister, "Uber Krystallisation des Eialbumins," Zeitsch. f. physiol.
Chem., vol. xiv., 1890, and vol. xvi., 1892.

3 Hopkins and Pinkus, "Observations on the Crystallisation of Proteids,"
Jour, of Physiol., vol. xxiii., 1898.

4 Osborne and Campbell, Jour. Amer. Chem. Soc., vol. xxii., 1900.

5 Bondzinski and Zoja, "Uber die fraktionierte Krystallisation des
Eieralbumins," Zeitsch. f. physiol. Chem., vol. xix., 1894.

6 Willcock and Hardy, " Preliminary Note upon the Presence of Phosphorus
in Crystalline Egg Albumen," Proc. Cambridge Philosophical Soc., 1907.

7 Tarchanoff, " Uber die Verschiedenheiten des Eiereiweisses bei befiedert
geborenen (Nestfliichter) und bei nakt geborenen (Nesthocker) Vb'geln,"
PfliigeSs Arch., vol. xxxi., 1883. Tarchanoff, '' Uber Hu'hnereier mit durch-
sichtigem Eiweiss," PflngeSs Arch., vol. xxxix., 1883.

288

THE PHYSIOLOGY OF REPRODUCTION

Further insight into the composition of some of the proteins of
the egg has been gained by means of the methods devised within
recent years by E. Fischer and by Kossel, for the study of the
constitution of the protein substances. By boiling with hydrochloric
acid the proteins are split into the constituent amino acids and
diamino acids, which are then determined as nearly quantitatively as
possible.1

In the results given in tabular form below, the figures represent
percentages, those under " total " indicating the percentage recovered
in the form of amino acids and diamino acids. The absence of any
one constituent is indicated by 0, the presence without quantitative
estimation by +, while — indicates that investigations as to the
presence or absence of a particular constituent have not been made.

Egg Albumen
(Osborne, Jones,
and Leaven-
worth).

Vitellin
(Osborne and
Jones).

Keratin from
Egg-Membrane
(Abderhalden
and Ebstein).

Per Cent.

Per Cent.

Per Cent.

Glycine -

0

0

3-9

Alanine -

2'2

0-8

3-5

Valine

2'5

1-9

I'l

Leucine ...

107

9-9

7'4

Phenylalanine

5-1

2-6

—

Tyrosine ...

1-8

3-4

0

Serine -

—

_

Cystine - - 0'4

—

7-6

Proline - 3'6

4-2

4-0

Oxyproline - - - -

-

—

Aspartic acid - 2'2

2-2

1-1

Glutamic acid - - - j 9*1

13-0

8-1

Tryptophane - ; -f-

+

-

Diamino f Argmme -
• -, -| Lysme
acids iHistidine-

4-9
3-8
1-7

7-r>
4-8
1-9

_

Total

48-0

52-0

36-7

Of the simpler nitrogenous substances creatin and guanidin
have been investigated in some detail. Creatin,2 which contains
the guanidin group in combination with acetic acid, is absent from
the hen's egg. It does not appear in the developing chick until the
twelfth day, when a trace is present. It then rapidly increases until
the hatching period. Guanidin 3 is present in small amount in the

1 For fuller reference see Plimmer, The Chemical Constitution of the Proteins,
3rd Edition, London, 1917, in the series of Monographs on Biochemistry ; and
Abderhalden, Lehrbuc,h der Physiologischen Chemie.

2 E. Mellanby, "Creatin and Creatinin," Jour, of Physiol., vol. xxxvi., 1908.

3 Burns, "On the Precursor of Creatin in Chick Muscle," Biochcm. Jour.,
vol. x., 1916.

BIOCHEMISTRY OF THE SEXUAL ORGANS 289

egg — about O'l per cent. During the first twelve days of incubation
it increases to about five times the initial value and then, after a
slight fall, remains stationary during the rest of development.
Guanidin is probably split off from arginine, which contains the
guanidin group in combination with an amino acid.

With regard to the question of the presence of ferments and their
significance we are on very difficult ground. We must here clearly
distinguish between endo-enzymes and secreted enzymes. The
endo-enzymes comprise all those enzymes which are so closely bound
up with the protoplasm that they can be isolated only after the cell
has been destroyed. Their sphere of activity is therefore limited to
the inside of the cell. Such endo-enzymes are present in every organ,
and have also been found in the egg,1 producing proteolysis and
lipolysis. But since such endo-enzymes are present in many, if not
in all cells, no special significance can be attached to their presence
in the eggs.

The presence in the egg of secreted ferments analogous to the
ferments which can be obtained by simple extraction from the
digestive glands of the adult animal, would allow of more definite
conclusions. The presence of such ferments has as yet not been
proved with certainty, although the diastatic action of egg-yolk
observed by Miiller and Masuyama2 points to the presence of a
diastase analogous to the ptyalin of the saliva.

Lower Vertebrates

The covering of the eggs of the lower Vertebrates is either of
the nature of a keratin, a scleroprotein rich in sulphur, similar to the
membrane of birds' eggs, or it is a mucoid substance. In reptiles,
like Calotes jubatus and Crocodilus biporcatus, and in Elasmobranchs,
like Raja, and Scy Ilium, the membrane is stated to consist of a
keratin.3 In the membrane of the eggs of Tropidonotus* the British
grass snake, a substance has been found which is free from sulphur
and resembles the elastin which constitutes the elastic fibre.s of
mammalian connective tissue. A similar substance is stated to occur
in the egg-membrane of Mnstelus Iccvis.5 But these data are very
scanty and hardly convincing. In Amphibians like the frog the

1 Wohlgemuth, "Tiber das Vorkommen von Fermenten im Hiihnerei,"
Festschrift fit r Salkoivski, 1904.

2 Miiller and Masuyama, "Uber ein diastatisches Ferment im Hiihnerei,"
Zeitsch. f. BM., vol. xxxix., 1900.

3 Krukenberg, Vergleichende Phj/siologische Btudien, II. Reihe, 1 Abteilung,
1882. Neumeister, " Uber die Eischalenhaute von Echidna und der Wirbeltiere
im allgemeinen," Zeitsch. f. Biol., vol. xiii., 1895.

4 Hilger, " Ueber die Chemischen Bestandteile des Reptilieneies," Berichte
der deutschen chem. Gesellschaft, vol. vi., 1873.

5 Krukenberg, loc. cit., 2 Abteilung, 1882.

290 THE PHYSIOLOGY OF REPRODUCTION

membrane has been found to consist of pure mucin.1 In Teleostean
fishes it has been investigated in the case of the perch,2 and found
to be of the nature of a mucin.

It would be interesting to find out by systematic investigations,
such as those of Pregl 3 and Bnchtala,4 whether the chemical nature
of the substances protecting the egg varies with the different
zoological classes, or whether there is a chemical adaptation to
external environment.

The investigations of Hammarsten brought to light the interesting
fact that a chemical change takes place in the cover of the eggs
during ripening. The immature eggs swell with water, and a
mucilaginous solution of mucus is formed, from which the mucin
may be precipitated by the addition of acetic acid. If mature eggs
are treated with water they do not swell. The water dissolves out
the contents of the egg and the empty covers of the eggs remain,
and can be transformed into mucin by weak alkali. During the
ripening of the eggs there is therefore a change from mucin to
mucinogen.

The composition of the eggs of fishes is essentially the same as
that of birds' eggs. From the eggs of salted herrings Hugounenq has
obtained the following figures calculated in percentage of the dried
material : —

Per Cent.

Pure fats 10'35

Phosphorieed fats 6 '53

Keratin 2'27

Protein (" clupeovin ") - 81 '47

The organic constituents consist chiefly of protein, fats, and
phosphorised fats, with some cholesterin.

The following analysis of the ash of caviar 5 gives an idea of the
composition of the ash of the eggs of fishes : —

Total ash - K2O. Na2O. CaO. Fe20:i. P205. 01.

7'70 per cent. - 3'33 3077 5'02 0'22 10'55 47 '44

Iii the egg the protein is present in the form of a phosphoprotein.
Valenciennes and Fre"my, who were the first to isolate this substance,
called it Ichthulin. Later Walther showed that this substance very
closely resembles the vitellin present in birds' eggs. On peptic
digestion it yields an iron-containing pseudonuclein. A similar

1 Giacosa, "Etudes sur la Composition chimique de 1'CEuf et de ses
Enveloppes chez la Grenouille commune," Zeitsch.f.physiol. Chem., vol. vii., 1883.

- Hammai'sten, " Chemie des Fischeies," Skan'din. Arch. f. Physiol., vol. xvii.,
1905.

3 Pregl, "tiber die Eihaute von Scyllium stellare und ihre Abbauprodukte,"
Zeitsch. f. pkysiol. t'hem., vol. Ivi., 1908.

4 Buchtala, ibid,

5 Albu and Neuberg, Minerulstoffwechsel, p. 241.

BIOCHEMISTRY OF THE SEXUAL ORGANS 291

substance containing phosphorus and iron was isolated from the
eggs of the salmon by Noel Paton, from cods' eggs by Levene, and
from perches' eggs by Hammarsten.1 The statement by Walther
that ichthulin, on boiling with mineral acids, splits off a reducing
sugar and differs in this respect from vitellin has not been confirmed
by the later workers.

A protein, clupeovin, which differs in many respects from these
ichthulins has been isolated from the eggs of herrings by Hugounenq,2
and Galimard has obtained a similar substance from the eggs of
frogs which he calls ranovin. Most authorities, however, doubt the
chemical individuality of these proteins.

Ichthulin is probably identical with the crystalline material
observed in the eggs of the tortoise, the frog, the shark, and other
fishes, which is known morphologically under the name of yolk-
spherules or " Dotterplattchen." The unripe eggs of the perch are
embedded in a fluid from which a protein of the nature of a globulin
has been isolated. This protein received the name " percaglobulin." 3
It is rich in sulphur, and is precipitated by weak hydrochloric acid.
It has an astringent taste, and possesses the remarkable property of
forming precipitates with some glucoproteins such as ovomucoid, and
with polysaccharides such as glycogen and starch. This substance
could not be found when the eggs were mature, and does not appear
to be present in the ovaries of other fishes.

Very important and interesting results have been obtained by
systematic chemical examinations of the muscles and ovaries of the
salmon 4 and of the herring 5 at different seasons. Extensive chemical
changes take place in these animals during the period of their
reproductive activity. The reproductive organs develop at the
expense of the muscles, which dimmish in weight. This is best
seen in the salmon, since this animal does not take any nourishment
during its passage up the rivers. In the herring the conditions are
not quite so simple, because the herring feeds until spawning occurs,
although less food is taken in the later months.

In the case of the salmon, then, the ovaries are built up from
material contained in the muscle. The most marked change in the

1 Hammarsten, "Chemie des Fischeies," Skandin. Arch. f. Physiol., vol. xvii.,
1905. This paper contains a detailed review of previous work done on this
subject.

2 Hugounenq, "Sur une albumine extraite des oaufs des poissons," Compt.
Rend., vol. cxxxviii., 1904. Galimard, ibid.

3 Morner, " Percaglobulin ein charakteristischer Eiweisskorper aus dem
Ovarium des Barsches," Zeitsch. f. physiol. Chem., vol. xl.

4 Miescher, Histochemische und physiologische Arbeiten. Noel Paton and
others, " Report of Investigations on the Life-History of the Salmon in Fresh
Water," Report to the Fishery Board for Scotland, 1898.

5 Milroy, "Changes in the Chemical Composition of the Herring during
the Reproductive Period," Biochem. Jour., vol. iii., 1908, p. 366.

292 THE PHYSIOLOGY OF REPRODUCTION

muscle during that period is a loss of fat, with which the muscles
are loaded when the salmon leaves the sea. The protein constituents
of the muscle also diminish, but not to the same extent as the fat.
There is, further, a disappearance of the inorganic phosphates of the
muscle. From these substances the ovaries build up their essential
constituents — the phosphoprotein ichthulin and the phosphorised
fats. The source of the choline which is contained in the phos-
phorised fats is not yet clear. This formation by the ovaries of
phosphorised fats out of fats and inorganic phosphates points to the
important function which these organic phosphorus compounds have
to fulfil in the developing organism (see above).

Not all the fat which disappears from the muscles reappears in
the ovaries as phosphorised fats. A portion of it serves as a source
of energy for the animal. The same applies to part of the protein
of the muscle.

The iron contained in organic combination in the ichthulin of
the ova is derived partly from the muscle and partly also from the
blood.

Associated with the accumulation of fat in the muscles there is a
storing of a lipochrome or lutein, the characteristic pink pigment of
the flesh of the salmon. During its sojourn in the river this pigment
disappears in part from the muscles and is transferred with the fat
to the ova. This pink pigment is probably formed from another
yellow pigment, which is also present in the salmon, and which is
widely distributed in the animal kingdom, always closely associated
with fat. It is possible that the ingestion and deposition of fat
containing this yellow pigment is responsible for the formation of
the pink pigment.

The chemical composition of the eggs of Invertebrates does not
appear to be essentially different from that of the Vertebrate eggs.
The covering of the egg, which is often stated to be chitin, has been
investigated by Tichomiroff1 in the egg of Bonibyx mori. He found
it to be a protein body rich in sulphur, and similar to the keratin
substances of which the membrane of the hen's egg is composed.
The covering of the eggs of a cephalopod — the cuttlefish — was
investigated by von Fiirth.2

These eggs are united by their capsules, which are often coloured
black by pigment, and form what are popularly known as " sea-grapes."
The covering or capsule is secreted by two "nidamental glands,"

1 Tichomiroff, " Chemische Studien tiber die Entwicklung der Insekteneier,"
Zeitsch.f. physiol. Chem., vol. ix., 1885.

2 Von FUrth, " Uber Glycoproteide niederer Tiere," Hofmeister1* Beitrage,
vol. i., 1901.

BIOCHEMISTRY OF THE SEXUAL ORGANS 293

which open into the oviduct, and it is interesting to note that the
substance secreted by these sexual glands is a mucoid substance very
similar to the pseudomucin found in cysts of the human ovary (see
Mammals, p. 276).

The protein substances in the eggs of Invertebrates have not been
closely investigated. Vitellin is said to occur.

The eggs of insects are comparatively rich in phosphorised fats.
By extraction with alcohol and ether, Dubois1 isolated from locusts'
eggs a yellowish oil containing 1/92 per cent, phosphorus.

Glycogen, purine bases, and cholesterin have been found in the
eggs of Bombyx. The changes which take place in the chemical
composition of these eggs, during incubation, have been investigated
by Tichomiroff.2

The following table shows that a considerable amount of purine
bases are formed during incubation. At the same time the fat and
glycogen diminish in amount, while the cholesterin remains practi-
cally unchanged and the phosphorised fats increase slightly in
amount.

Before

After

Incubation.

Incubation.

Per Cent.

Per Cent.

Purine bases

0-02

0-2

Glycogen -

1-98

074

Present in f Fat

8'08

4-37

ethereal \ Phosphorised fat -

1-04

1-74

extract I Cholesterin

0-40

0-35

On the whole the changes are similar to those observed in hens'
eggs, except that glycogen is present in considerable quantities in
the egg and disappears during development as well as the fat, while
the phosphorised fats are apparently not utilised as a source of
chemical energy. The " energy of development " is very considerable,
and, calculated as a percentage of the chemical energy contained' in
the whole egg, is as great as in the case of the developing hen's egg.3

Other experiments on different insects 4 have confirmed the fact
that in these animals, as in birds, the main source of the energy
which is used up during development is fat. No nitrogen is lost,

1 Dubois, "Sur 1'huile d'CEufs de la Sauterelle d'AIgerie (Acridium
pelerimim)" Compt. llend., vol. cxvi., 1893.

2 Tichomiroff, loc. cit.

'3 Farkas, " Uber den Energieumsatz des Seidenspinners wahrend der
Entwicklung im Ei u. wahrend der Metamorphose," Pfliiqer's Arch., vol. xcviii.,
1903.

4 Weinland, Zeitsch. f. Biol., vol. xlvii., 1905 ; vol. xlviii., 1907 ; vol. li., 1908 ;
vol. Hi., 1909. Tangl, Pftiiger's Arch., vol. cxxx., 1909.

294 THE PHYSIOLOGY OF REPRODUCTION

but some of the protein material undergoes partial oxidation, to
uric acid, and may thus contribute to the " energy of development."
Whether the glycogen which disappears during development serves
as a source of energy is doubtful. The chitin which is deposited in
the cuticle of insects is a compound built up mainly of carbohydrate-
groups, and it seems likely that these carbohydrate-groups are derived
from the glycogen, which thus contributes to the formation of the
cuticle. It is interesting to note that glycogen appears to fulfil a
similar function in the developing rabbit, where it also contri-
butes to the building up of the growing tissues.1 It appears
indeed to be a general law that carbohydrate material is essential
for growth.

Another point which emerges from these considerations of
comparative biochemistry is that the synthetic capacity of the
developing ovum remains constant throughout the different classes
of animals which have so far been investigated. Thus in every case
investigated the developing ovum has the power of synthesising the
purine bases, while conversely it is unable to synthesise cholesterin,
or at any rate does not require to do so, since cholesterin is always
present in the egg, in amounts equal to or greater than those found
in the developed embryo. Only one exception to this rule has so
far been observed : in the starfish egg cholesterin is absent.2

The pigments have been studied especially in the eggs of Crustacea.
From the eggs of Maja squinado, Maly3 isolated two pigments —
a red pigment, Vitellorubin, which is extremely sensitive to light,
and a yellow pigment, Vitellolutein. These pigments belong to
the lipochromes or luteins, which have been mentioned above.
Krukenberg4 has examined the pigments of a number of other
Invertebrates. All these lipochromes have characteristic absorption
spectra.

The lipochromes of Maja are of special interest, because a similar
pigment, Tetronerythrin, has been found in the blood of Maja and
other Crustacea. The amount present in the blood shows consider-
able variation. According to Heim 5 it is completely absent in the
blood of the male, and appears in the blood of the female during
ovulation. At this period also the ovaries, which usually have' a
yellowish or whitish colour, become first bright yellow and then red.

1 Lochhead and Cramer, loc. tit.

2 Mathews, "An important Chemical Difference between the Eggs of the
Sea-Urchin and those of the Starfish," Jour. Biol. Chem., vol. xiv., 1913.

3 Maly, "Uber die Dotterpigmente," Berichte der Akademie der M7,w?z-
schaften, in Wien, vol. Ixxxiii., 1881.

* Krukenberg, Vergleichende physiologische Studien, II. Eeihe, 3 Abteilung,
1882, p. 6.

5 Heim, " Sur les Pigments des CEufs des Crustaces," Compt. Rend. Soc. BioL,
vol. xliv., 1892, p. 467.

BIOCHEMISTRY OF THE SEXUAL ORGANS 295

In Helm's l view this lipochrome is not formed in the ovary but in
some other organ of the body, and passes at the period of ovulation
into the blood, which carries it to the ovaries.

The same author, together with Abelous,2 has proved the existence
of some ferments in watery and glycerine extracts of the eggs of
various Crustacea. A diastatic, a tryptic, and an inverting ferment
were found. They are stated to increase in strength during the
maturation of the ovum.

Heim's observations on the appearance of a lutein in the blood of
the female during ovulation have acquired great significance from
the remarkable work of Geoffrey Smith 3 on crustaceans. In these
animals the " liver," which corresponds to almost the entire digestive
and metabolic apparatus of the higher animals, varies greatly in its
composition according to the condition of the crab in respect to two
functions — reproduction and moulting. The quantitative variations,
which are reflected also in the composition of the blood, refer to the
amounts of glycogen and of fat present. In addition there are
qualitative changes in the nature of the lipochrome circulating in the
blood. Thus in male crabs (Carcinus mcenas) the glycogen and fat-
content of the liver is low immediately after moulting and the blood
is colourless and carries little fat. In the intermediate period
bet\veen two moults there is an increase in the glycogen and fat-
content of the liver. The blood is pink owing to the presence of the
red pigment tetronerythrin, which is deposited in the shell. The fat-
content of the blood, however, remains low (0'08 per cent.).

In female crabs which are maturing their ovaries preparatory to
breeding, the liver is rich in fat and contains a fair amount of
glycogen. The blood is very rich in fat (0*2 per cent.). But its most
striking feature is its light yellow colour, due to the presence of a
yellow lutein which is being formed in the liver and carried by the
blood to the ovaries, where it is deposited in the yolk of the eggs.
After the eggs have been shed the blood becomes again colourless.
The resulting secondary sexual characters of the male are, therefore,
that the external colour is redder than that of the female, and. that
the male is larger.

If now crabs of both sexes are infected with Sacculina they cease
to grow, moult or reproduce, but they all present the same condition,
namely that of a female crab with mature ovaries, and that occurs
even with male crabs. The glycogen-content is low, the fat-content

1 Helm, Etudes sur le Sang des Crustaces, Paris, 1892.

- Abelous and Heim, " Sur les Ferments des (Eufs des Crustaces," Compt.
Rend. Soc. Bid., vol. xliii., 1891, p. 273.

3 Geoffrey Smith, " The Effect of Reproductive Cycle on Glycogen and Fat
Metabolism in Crustacea," British Assoc., 1913, p. 670. See also British Assoc.,
1910, p. 635 ; 1911, p. 414.

296 THE PHYSIOLOGY OF REPRODUCTION

high. Lutein is being formed actively in the liver, which is yellow.
But the lutein does not appear in the blood, probably because the
sacculina roots absorb it.

This production in the male crab of a metabolism of the female
type by infection with Sacculina may not stop merely at the appear-
ance of female secondary sexual characters in the male,, but may go
so far that ova are produced in the testes.

These remarkable facts have led Doncaster1 to assume that all
individuals contain potentially the characters for both sexes — are, in
fact, potential hermaphrodites. Sex is determined by an additional
factor which suppresses the characters of one sex and causes those of
the other sex to appear. The sex-determining factor does not
introduce the characters of the corresponding sex, but merely
releases them. And it does this by determining a certain type of
metabolism. In other words, metabolism determines sex, not sex

metabolism.

•^

THE MALE GENERATIVE OKGAXS
The Semen

The semen, i.e. the fluid discharged by an ejaculation, is the
secretory product of the testis, epididymis, vesiculse seminales,
prostate and Littre"s gland. In man it is a thick, viscous, yellowish,
opalescent fluid, which after ejaculation solidifies at first and after-
wards becomes fluid again. It has a peculiar smell, which becomes
even more noticeable on heating. Its reaction is alkaline. Its
specific gravity lies between T02 and 1*04. The amount discharged
in an ejaculation is given differently by different authors, and
probably varies with different individuals, and even with the same
individual at different times. From the figures given in the literature
5 gin. may be taken to be the average amount.2 In a normal
emission of man Lode calculated that there are about 226 million
spermatozoa, and that about 340,000 million must be produced in an
individual between the ages of twenty-five and fifty-five.

The different classes of animals show great differences in the
volume of semen ejaculated and in the relative proportion between
the spermatozoa and the liquid part of the semen in which they are
suspended.2 The semen of different animals also differs in its

1 Doncaster, "The Physiology of Sex Determination," British Assoc., 1913,
p. 671.

2 Acton, Functions and Disorders of the Reproductive Organs, 3rd Edition,
London, 1862. Lode, " Untersuchungen iiber die Zahlen und Regenerations
Verhaltnisse der Spermatozoiden bei Hund und Mensch," Pftilger's Arch., vol. i.,
1891. Mantegazza, Gaz. Med. ItaL, Lombardia, 1866, quoted from Lode.

3 Iwanoff, " Le Sperme de quelques Mammiferes," Compt. Rend. >SV. de
vol. Ixxx., 1917.

BIOCHEMISTRY OF THE SEXUAL ORGANS 297

appearance, consistency and smell. The amount of semen ejaculated
by dogs varies from 0*5 to 30 or 40 c.c. This depends partly on the
size of the animal but partly also on its general condition. The
amount of spermatozoa present is relatively small in proportion to
the liquid part of the semen. In sheep the proportion is greater but
the total amount ejaculated does not exceed 2 to 5 c.c. In the horse
the volume is on the average 50 to 100 c.c. but may sometimes
exceed 300 c.c.

Slowtzoff l has made comparative analyses of the semen of man.
horse, and dog, which have given the following figures : —

Dog.

Horse.

.
Man.

Water 97*560

95*705

90-321

Total solids - - - 2 '450

4-295

9-679

Ash- - - 0-687

0-915

0-901

Organic matter 1*763

3-380

8-778

All protein matter - 1*259

2-238

2-854

Albumins, globulins, nucleo-proteins - 0*886
Mucin - 0'057

1*142
0*559

i 2-579

Alburnoses - - 1 0'314

0*537

0-412

Lipoids - - 0-182

0-172

0-208

Cholesterin 0'00075

0-0042

1

Various organic substances ("Extractives") 0*312

1-090

5-716

Human semen consists, therefore, roughly of ninety per cent,
water and ten per cent, solids, which, on incineration, yield about
one per cent, of ash. About one-fourth part of the solids consists of
proteins, of which a nucleoprotein, traces of albumen and mucin, and
an albuinose-like substance have been identified. The semen of the
dog and horse differs in containing more water. This difference is
made up by the presence of a large amount of various organic
substances in human semen, which have not been clearly identified.

In the ash of human semen, K, Na, Ca, Mg, P, Fe, and S have
been found.

The quantitative analysis of the ash reveals a remarkably large
amount of calcium and phosphoric acid — about twenty per cent.
Ca and thirty per cent. P205. In man the amount of calcium
excreted in one ejaculation is, therefore, about O'Ol gin., and exceeds
that contained in an equal quantity of lime-water. Analyses of the
ash of the semen of other Mammals do not appear to have been
made, but it is unlikely that there are any essential differences.
Since during the breeding season about fifty sheep are served by one
ram, it is evident that a profound change must take place in the

1 Slowtzott', " Sur la Composition biochemique du Liquide spermatique,"
Compt. Rend. 8oc. de Biol., vol. Ixxix., 1916. See also Zeitsch. f. p/iysioL Ch<'m.,
vol. xxxv., 1902.

10 A

298 THE PHYSIOLOGY OF REPRODUCTION

metabolism of phosphorus and calcium during that period. Is it not
possible that the effects which are usually ascribed to a hypothetical
" internal secretion " of the testis are partly due to such a direct
connection with the metabolism of the body?

The nature of the influence which the sexual glands exert upon
the metabolism of the body is very complex, and has not yet been
fully cleared up. Various observers have obtained very contradictory
results. Since this subject will be dealt with in another chapter, we
will refer to it here only in so far as it has any bearing on the calcium
and phosphorus metabolism. On this point there is conclusive
evidence of a morphological nature both for the male and for the
female organism. Castration, if performed in youth, leads to a marked
increase in the growth of the long bones. This fact, which is due
to a retardation of the process of endochondral ossification taking
place in these bones, accounts for the increase in stature-of eunuchs
and of castrated animals (see p. 323).

Similar evidence, although of a more complex character, is afforded
in the case of the female by the relationship which undoubtedly exists
between the ovaries and osteoinalacia, a disease consisting mainly in
a decalcification of the bones. It is produced probably by an abnormal
function of the ovaries, since removal of the ovaries markedly
improves, and sometimes cures, this condition (see p. 389). In
pregnancy and parturition there is what one might call a " physiological
osteoinalacia " of the pelvic bones ; and the activity of the mammary
gland during lactation must necessarily bring about an increased
calcium metabolism, since milk contains a very large amount of this
element.

The organic substances in the semen may be divided into two
groups. If the semen is examined microscopically it is found that it
contains, on the one hand, cellular elements — viz. the spermatozoa
and lymphocytes, partly in a state of degeneration ; on the other hand,
organic material which is partly amorphous and partly crystalline.

The amorphous material consists of : —

1. Fine albuminous granules, intermixed with a few fat globules
and pigmented granules.

2. Small globules of about half the size of a red blood corpuscle,
consisting of "a lipoid substance.

3. Oval amyloid bodies composed of concentric layers. These are,
however, not invariably found.

4. The so-called " sympexions " of Robin, oval concrements of a
wax -like substance, the nature of which is not known.1

} Cohen, " Die krystallinischen Btldungen des mannlichen Genitaltraktus,"
Centralblatt f. al!g. Pathologic u. pnthol. Anatomie, vol. x>, 1899. (This paper
gives a very complete bibliography.)

BIOCHEMISTRY OF THE SEXUAL ORGANS 299

The crystalline substances appear only when the semen is
inspissated. They present various forms — prisms, rosettes, etc., and
according to Schreiner,1 who investigated the substance very fully,
these crystals are identical with those found on the surface of old
anatomical preparations which have been kept in alcohol, the so-called
" Bottcher's crystals." They are insoluble in alcohol, ether, -and
chloroform, soluble in hot water, in formol, dilute alkalis and alkali
carbonates, and in dilute acids. They are coloured black by a solution
of iodine in potassium iodide — " Florence's reagent " (see p. 301). Like
many ammonium-bases spermine gives a characteristic colour reaction
with alloxan.2 On evaporating a solution of spermine to which a
saturated solution of alloxan has been added, a red colour appears,
which changes into violet on the addition of alkali. The spermine
crystals are not identical, as was formerly believed, with the crystals
found in the blood of leucsemic patients (" Zenker's crystals "), or
with the " Charcot-Leyden crystals " which occur in the sputum
of asthmatic persons.

Their chemical nature is still a matter of doubt. According to
Schreiner, they are the phosphate of an organic base spermine, C2H5N,
which Ladenburg and Abel3 believed to be aethylenimin, C2H4NH.
This is disputed, however, by Majert and Schmidt,4 who ascribe to the
base the formula C5H14N"2, and by Poehl,5 who has attributed very
remarkable properties to this substance.

According to Poehl, spermine is possessed of marked pharma-
cological properties, and has a powerful^ influence on the metabolism.
It is recommended by Poehl as a valuable therapeutic agent. His
statements have not been confirmed by other observers — for example
Dixon 6 — and his views are now not generally accepted.

Choline, which gives the same reactions as spermine with iodine
and alloxan, has also been stated to occur in the semen.

The various glands of the genital tract contribute to the formation
of the semen in the following way : —

The spermatozoa are formed in the testis, which secretes an
albuminous fluid as the medium in which the spermatozoa move
about. Crystals smaller than the crystals of spermine-phosphate

1 Schreiner, " Uber eine neue organische Basis in thierischen Organismen,'
Liebig's Annalen, vol. cxciv., 1878.

2 Poehl, " Weitere Mitteilungen liber Spermin," Berliner klin. Wochenschrift,
1891. See also Huntley and Wootton, Jour. C/iem. Soc., vol. xcix., 1911.

3 Ladenburg and Abel, " Uber das Aethylenimin," Ber. der deutschen chem.
(j'esellgchaft, vol. xxi., 1888.

4 Majert and Schmidt, "Uber das Piperazin," Ber. der deutschen chem.
(jfesellsc/iaft, vol. xxiii., 1890.

5 Poehl, Die Physiologisch-Chemisctien Grwndlagen der Spei'mintherapie,
St. Petersburg, 1898/

6 Dixon, "The Composition and Action of Orchitic Extracts," Jour, of
PkysioL, vol. xxvi., 1901.

300 THE PHYSIOLOGY OF REPRODUCTION

have been observed by Lubarsch l in the tubules of the testis. They
are insoluble in formol and fifty per cent, acetic acid, and swell up
under the action of alkali. Other crystalloid rod-like formations in
the interstitial cells have been described by Reinke2 and von
Bardeleben.3 The nature of these crystals, which have been found
so far only in human testes, is unknown. Amyloid bodies, which are
coloured blue with difficulty by iodine, have been observed by Dareste.

The secretion of the epididymis has not been chemically investi-
gated. The vesiculse seminales secrete a substance of a protein
nature 4 which in the rat and guinea-pig probably belongs to the group
of histones.5 The secretion in these animals is a white viscid fluid
and has a faintly alkaline reaction.

In the guinea-pig and the rat the secretion by the vesiculae
seminales clots if brought in contact with the secretion of the
glandular structure adjacent to the seminal vesicles and termed by
Walker, who discovered it and lias studied it in detail, the
"coagulating gland." This property is perhaps a means whereby
fertilisation is ensured by the formation of a clot in the outer portion
of the vagina which prevents the escape of semen.

The prostate gland secretes an opaque fluid having a neutral
reaction (which may become alkaline in inflammatory conditions of
the prostate). It contains sperinine,6 which, when brought together
with the phosphates secreted by other genital glands, forms the
characteristic " Bottcher's crystals." The secretion of the prostate
has the property of stimulating intensely the movements of the
spermatozoa. This fact, which has been frequently confirmed,7 has
given rise to very exaggerated ideas about the mechanism of this
hypothetical substance until it was found that this action is not at
all specific but is given also by serum and depends simply on the
CO2 binding power of the prostatic secretion. The explanation is
probably to be found in the fact observed long ago by Kolliker,8 that the

1 Lubarsch, "Uber das Vorkommen Krystallinischer und Krystalloider
Bildungen in den Zellen des Menschlichen Hodens," Virchoiv's Arch., vol. cxlv.,
1896.

2 Reinke, "Beitrage zur Histologie des Menschen," Arc/iiv f. mih'osicop.
Anatomie, vol. xlvii., 1896.

3 Bardeleben, " Beitrage zur Histologie des Hodens und zur Spermatogenese
beim Menschen," Archiv. f. Anat. u. Physiol., Anat. Abteilung, Supplement, 1897.

4 Landwehr, " Uber den Eiweisskorper der vesicula seminalis der Meer-
schweinchen," Pjluget's Arch., vol. xxiii., 1880.

5 Walker (G.), "The Nature of the Secretion of the Vesiculae Seminales, etc.,"
Johns Hopkins Hospital Bidletin, TO!, xxi., 1910.

6 Furbringer, " Die Storungen der Geschlechtsf unktion des Menschen " ; in
Nothnagel. Pathologic u. Therapie, vol. xix., Part III., 1895.

7 See von Fiirth, Probleme der physiol. u. path. Chem., Leipzig, Vogel, p. 342,
vol. L, 1912.

s Kolliker, " Physiologische Studien iiber Samenttiissigkeit," Zeitsch. /.
nnsxenschafll. Zool., vol. vii., 1856. Gray, " Note on the Relation of Spermatozoa
to Electrolytes," Q-ttar. Jour. Nicr. Science, vol. Ixi., 1915.

BIOCHEMISTRY OF THE SEXUAL ORGANS 301

movements of spermatozoa are inactivated by acids. Now spermatozoa
constantly give off CO2 and in doing so make the fluid in which they
are suspended sufficiently acid to inhibit their own movements. This
self-inhibition acts as a protective mechanism. Spermatozoa are
endowed with a definite store of energy, which since they are isolated
cannot be replenished. Their capacity for locomotion and their length
of life is therefore limited and depends on the rate with which they
expend their store of energy. But whether their life be long or
short, the total amount of energy which they can release as measured
by the total amount of 002 which they excrete is constant.1
They immobilise themselves in the testis and efferent ducts by means
of their own CO2 excretion and thus save their energy until the
moment of ejaculation when the C02 is absorbed by the prostatic
secretion.

The secretion of the prostate also contains the substance which
gives the characteristic smell to the ejaculated semen, the lecithin-
like globules, and a protein substance, which from its reactions
cannot easily be classified. The statement that this protein is an
albumose is probably not correct, since albumoses have never been
found to occur in a living cell. Camus and Gley2 found in the
prostatic secretion of some animals a ferment, vesiculase, which has
the property of coagulating the fluid in the vesicuLe seminales. The
presence of this ferment in the ejaculated semen produces the
formation of a coagulum. This ferment appears to have the function
of ensuring fertilisation, since it occurs only in those species where
the contact between male and female is of very short duration
(see p. 248). Walker has shown, however (see above), that this
coagulating property is not exhibited by the secretion of the prostate
gland, but is found in the secretion of a separate glandular organ
which he terms the coagulating gland, and which is histologically
and functionally different from the prostate.

Cowper's glands secrete a stringy mucinous substance.

If a solution of iodine in potassium iodide is added to semen,
brown crystals are formed (Florence's reaction). This reaction is
common to many substances belonging to the group of organic
ammonium bases. One of the best-known members of this group
is choline, which forms part of the lecithin molecule, and is, therefore,
a constituent of almost every animal cell. Probably the reaction is
not due to spermine (see p. 299), as Florence 4 states, but to choline,

1 Cohn, "Studies on the Physiology of Spermatozoa," Biol. Bull., vol. xxxiv.,
1918.

2 Camus and Gley, "Action Coagulante du Liquide Prostatique sur le
Contenu des Ve"sicules Seminales," Compt. Rend., vol. cxxiii., 1896.

4 Florence, "Du Sperme et des Taches du Sperme," Archives <? Anthropologie
Criminate, vol. xi., 1896 ; vol. xii., 1897.

302 THE PHYSIOLOGY OF REPRODUCTION

as Bocarius1 believes, since other secretions and tissue extracts which
do not contain spermirie give the same reaction.

Joestens2 considers that the crystals obtained in Florence's
reaction are perhaps merely iodine without any choline. Warmed
with a watery solution of gold tribrornide semen gives on rapid cooling
characteristic yellow crystals which are stated to be due to the
presence of both choline and spermine and which show accordingly
different forms.3

Another reaction for semen, which is much more specific, has
been discovered by Barberio. By the addition of picric acid, fine
rhombic or needle-shaped crystals are formed. It is doubtful which
substance is responsible for this reaction. The observations of
Littlejohn and Pirie4 show that the substance which forms the
crystalline picrate is secreted by the prostate and by Cowper's glands,
and, further, that this substance appears to be specific for human
semen, since a negative result is obtained with the semen of monkeys,
rabbits, and rats.

THE CHEMISTKY OF THE SPERMATOZOON 5

Owing to the brilliant work of Miescher,6 which has been con-
tinued by Kossel 7 and his pupils, our knowledge of the chemistry
of the spermatozoon is more complete than that of any other cell.

Thanks to the intelligent generosity of the head of a large fishery
concern in Bale, Miescher obtained a liberal supply of the milt of the
salmon, the sexual organs of which develop during the passage up
the Rhine, By controlling his mechanical manipulations by means
of histological observations Miescher was able to investigate separately
the different morphological elements of the spermatozoa. The tails of
the spermatozoa are very rich in phosphorised fats, and contain besides
a typical protein, cholesterin, and fat, in the following proportions : —

Per Cent.

Proteins - 41 '90

Phosphorised fats - - 31 '83

Cholesterin, fats - 26'27

1 Bocarius, " Zur Kenntniss der Substanz welche die Bildung von Florence-
schen Krystallen bedingt," Zeitscfi. f. physiol. Chem.t vol. xxxiv., 1902.

2 Joestens, " Experimentelle Untersuchungen iiber die Florence'sche
Beaktion," Vierteljahrschrift f. gerichtliche Medizin, vol. xlv., 1913.

3 De Dominicis, "Uber eine Spermareaktion mit Goldtribromiir, " Viertel-
jahrsch. f. gerichtliche Medizin, vol. xliv., 1912.

4 Littlejohn and Pirie, " The Micro-Chemical Tests for Semen," Edin. Med.
Jour., 1908. (This paper contains references to the literature.)

6 For a detailed account of this subject and the literature see Burrian,
"Chemie der Spermatozoen," I., in Ergebnisse der Physiologic, vol. iii., 1904;
and "Chemie der Spermatozoen," II., in Ergebnisse der Physiologic, vol. v., 1906.

6 Miescher, Histochemische und Physiologische Arbeiten. (fesammclt und
Herausgegeben von Seinen Freunden, vol. ii., Leipzig, 1897.

7 Kossel, " tiber die einfachsten Eiweisskorper," Biochemisches Centralblatt,
vol. v., Part I., 1906-07.

BIOCHEMISTRY OF THE SEXUAL ORGANS 303

Similar conditions were found to exist in the case of other fishes
and in the .case of the ox. The heads were found to contain only
traces of fat, lecithin and cholesterin, and to be composed almost
entirely of a substance very rich in phosphorus. This on further
investigation proved to be a combination of a basic substance, very
rich in nitrogen, which Miescher called protamine, and a substance
rich in phosphorus, having the nature of an acid and belonging to
the group of substances known as nucleinic acids, which occur, in
the nuclei of somatic cells in combination with protein substances
as the so-called imcleoproteins.

The comparative chemical investigations of Kossel proved that,
while the nucleinic acid radical present in the spermatozoa of various
species of fishes shows only very little variation, the basic part is
different for each species. It has, therefore, been found convenient
to distinguish these basic substances by separate names, derived from
the Latin names of the species of the fish in which they occur. The
basic substance of the head of the spermatozoon of the salmon is
salmine, that of the herring clupeine, and so on. Since they have
certain general chemical and physical characters in common they
have been classed together in a group, which has received the name
" Protamine," which was originally used by Miescher to denote the
basic substance in the spermatozoa of the salmon.

The protamines are strongly basic substances which absorb
carl >onic acid from the air. They are soluble in water, insoluble
in alcohol and ether; not coagulable by heat; free from sulphur.
They are very rich in nitrogen, the percentage amount varying
from .'53 per cent, to 25 per cent., while that of an albumen or
globulin is about 16 per cent. They give a strong biuret reaction.
Like other proteins, they are precipitated by tannic acid, phospho-
tungstic acid, picric acid, and ferrocyanic acid ; but while the
proteins are precipitated by these reagents in acid solution only,
the protamines, by virtue of their basic character, form a precipitate
with these reagents even in alkaline solution. They form compounds
with the salts of the heavy metals (copper, mercury, silver, platinum).
The protamines combine with many other protein substances in
neutral or faintly alkaline solution, so that a precipitate is formed
if, for example, a solution of protamine is added to a solution of
caseinogen.1

If injected into an animal they have a strongly toxic action, even
if small doses are given.2

Although differing in many respects from the protein substances,

1 Hunter (A.), "IJber die Verbindungen der Protamine niit anderen Eiweiss-
korpern," Zeitsch. f. physiol. (Jhem., vol. liii., 1907.

2 Thompson, "Die physiologische Wirkung der Protamine," Zeitsch. f.
physioL Chem., vol. xxix., 1899.

304 THE PHYSIOLOGY OF REPRODUCTION

the protamines have been shown by Kossel to have a constitution
so similar to that of the proteins that they are now considered to
represent one group of the protein substances.

The study of the products of hydrolytic decomposition shows that
while in the case of the typical proteins, such as the proteins of
muscle, of milk, or of the serum, the nitrogen is bound up in the
form of a great many different substances, e.y. tyrosine, leucine,
alanine, glycine, cystine, etc., of which as many as fifteen have been
isolated, the protamine molecule is composed of only a few constituent
substances. And further, while in the case of the typical proteins
the main bulk of the substance obtained on hydrolysis belongs to the
monoamino acids, the protamines are composed largely of the diamino
acids ; arginine, lysine, and histidine, which, from their basic nature
and the fact that they contain six carbon atoms, have received the
name " hexone-bases."

Of these the most important one is arginine, which, on boiling
with baryta, is decomposed into urea and diaminovalerianic acid
(ornithin), and has the structure —

NH2 NH2

NH=C— NH— CH2— CH2— CH2— CH— COOH

In salmine, for instance, eight-ninths of the nitrogen is bound up
as arginine, while the remainder of the nitrogen is present in the
form of monoamino acids, viz. serine, monoaminovalerianic acid and
proline, in the following proportions: 10 molecules of argiuine + 2
molecules of serine +2 molecules of proline +1 molecule of amino-
valerianic acid. Similar relations are found to exist in the case of
scombrine and clupeine. In both these protamines eight-ninths of
the total nitrogen is present in the form of arginine, which is
combined with alanine and proline in the case of scombrine, and
with alanine, proline, serine, and aminovalerianic acid in the case
of clupeine.

Since eight-ninths of the nitrogen of these three protamines is
present in the form of arginine, and since arginine contains four
nitrogen atoms, while the amino acids with which it is combined
contain only one nitrogen atom, it follows that in these three
protamines the number of arginine molecules must be twice as great
as the total number of monoamino acid molecules present in the
protamine molecule.

The investigations of Kossel and Pringle1 have shown that
substances can be obtained by partial hydrolysis of these protamines,
the so-called " protones," which represent intermediate decomposition

1 Kossel and Pringle, " Uber Protamine und Histone," Zcitsrh. f. phygiol.
Clem., vol. xlix., 1906.

BIOCHEMISTRY OF THE SEXUAL ORGANS 305

products between these protamiiies and the amino acid units of which
the protamines are built up, and that these protones again contain
eight-ninths of their total nitrogen in the form of arginine. It
follows, then, that the molecules of salmine, scombriue, and clupeine
have a symmetrical structure, and are built up of molecular complexes
containing always twice as many arginine molecules as monoamino
acid molecules.

In other protamines the amount of arginine is smaller, while lysine
is found to be present. At the same time the number of mouoamino
acids bound up in the protamine molecule increases, so that the
different protamines exhibit varying degrees of complexity. Ammonia
and certain monoamino acids (glycocoll, phenylalanine, glutaminic
acid, aspartic acid, the sulphur-containing cystine) are never present.

In some fishes — e.g. Gadus morrhua,1 Lota vidgarisz — the
basic substances isolated from the spermatozoa differ essentially
from the protamines, and resemble in character more the typical
proteins. Their nitrogen content varies between 16 per cent, and
18 per cent. On hydrolysis the yield of diamino acids is very much
smaller than in the case of the protamines. Only 30 to 40 per
cent, of diamino acids, among which arginine again preponderates,
are obtained. Accordingly they are not so strongly basic as the
protamines. They contain cystine. They are precipitated by
ammonia, a reaction which the protamines do not give. They
resemble in their behaviour substances which have been isolated
from the nuclei of somatic cells, e.g. the blood corpuscles of the
fowl, the thymus, etc., and which form another class of the protein
substances, to which the name histone has been given. In their
properties and their composition these substances, therefore, take a
place between the typical proteins and the protamines.

The substance isolated from the spermatozoa of the carp, cyprinine
(or rather the two cyprinines, since two slightly different substances
have been isolated), is on the border-line between the protamines
and the histones. The cyprinines do not contain any cystine, they
are not precipitated by ammonia, and only about thirty-five per cent,
of their total nitrogen is present in the form of diamino acids, mainly
as lysine in the one of the two cyprinines.3

The chemical differences which exist between the spermatozoa o/f
the different species and orders occur arbitrarily without reference to
zoological relationship.

1 Kossel and Kutscher, "Beitrage zur Kenntniss der Eiweisskorper,"
Zeitsch. f. physiol. Chem., vol. xxxi., 1900.

2 Elirstrom, " Uber ein neues Histon axis Fischsperma," Zeitsch. f. physiol.
0/iem., vol. xxxii.. 1901.

3 Kossel and Dakin, " Beitrag zum System der einfachsten Eiweisskorper,"
Zeitsch. f. physiol. Chem., vol. xl., 1904.

306 THE PHYSIOLOGY OF REPRODUCTION

The significance of the presence of histones in the spermatozoa of
some fishes becomes more apparent if the development of the sexual
organs is considered.

It was Miescher who pointed out that in the salmon the sexual
organs develop at the expense of the muscular system and that the
salmine deposited in the testis during the breeding season must be
derived from the proteins of the muscle, .since the fish does not
take any food during that period. A comparison between the
amount of arginiiie present in salmine and that present in the
muscle of the salmon, shows1 that all the arginine deposited as
salmine during the breeding season can be accounted for by the
arginiiie which becomes available by the involution of the muscular
elements.

This result would suggest that the formation of salmiue is not
due to a profound chemical alteration of the various constituents
of the muscle-proteins, transforming the divers substances into
arginiiie, but rather to a gradual enrichment in arginiue of the
muscle-protein by the splitting off of a number of the other con-
stituent substances.

The investigation of the unripe spermatozoa of the salmon 2 and
of the mackerel 3 has shown indeed that instead of a protamine a
histone is present, i.e. a substance which represents the transition
stage between the typical proteins and the protamines.

It would appear, therefore, that in the fishes the chemical
processes which lead to the formation of the spermatozoa consist of a
rearrangement of the constituents of the proteins of somatic tissue,
so that a gradual accumulation of the basic substances rich in
nitrogen takes place. This change leads at first to the formation of
histones, and in some species stops here. In the majority of cases
the change proceeds to the formation of substances belonging to
the protamines.

In some Invertebrates (Arbacia pustulosa* Sphcvrechinus granu-
laris5) the spermatozoa have been investigated and histones have
been found to be present.

Of the higher Vertebrates, the spermatozoa of the frog, the cock,

1 Kossel, "Einige Bemerkungen iiber die Bildung der Protamine im
Thierkorper," Zeitsch. f. physiol. C/iem., vol. xliv., 1905. "Weiss, "Unter-
suchungen iiber die Bildung des Lachs-Protamins," Zeitsch. f. physiol. Ckem.,
vol. Hi.. 1907.

2 Miescher, "Physiologisch-Chemische Untersuchungen iiber die Lachsmilch,"
Histochemische Arbeiten, Archiv f. Experimentelle Pathologie u. Pharmakologie,
vol. xxxvii., 1896-97.

3 Bang (I.), "Studien iiber Histon," Zeitsch. f. physiol. Chem., vol. xxvii., 1899.

4 Mathews, "Zur Chemie der Spermatozoon," Zeitsch. f. physiol. Chem.t
vol. xxiii., 1897.

5 Kossel, "liber die «infachsteii Eiweisskorper," Biochemisches Centmlblatt,
vol. v., 1906-07.

BIOCHEMISTRY OF THE SEXUAL ORGANS 307

the 'boar, and the bull have been examined,1 but neither protamines
nor histones were found.

The acid substance isolated from the spermatozoa, the nucleic
acid, does not show any variation in the different species and classes
of animals. It is, in fact, so similar to the nucleic acid present in
the nuclei of somatic cells, that it is now considered to be identical
with the nucleic acid prepared from the thynms, which has been
studied in great detail. These nucleic acids do not belong to the
proteins, but they exist in the cell always in combination with
proteins as nuclems or as nucleoproteins, according to the amount of
protein present in the combination.

The nucleic acids are dry, pulverulent, white substances of a
decidedly acid character, containing nine to ten per cent, of
phosphorus, not easily soluble in cold water, but readily dissolved
by alkalis or ammonia. They are precipitated from their solutions
by mineral acids and by alcohol. They form insoluble salts with the
heavy metals and with barium, calcium, and strontium. If pure,
they do not give the colour reactions for proteins. They rotate
polarised light to the right. A solution of nucleic acid, acidified
with acetic acid, gives a precipitate with protein solutions. By
boiling the watery solutions the nucleic acids are partially decom-
posed.2 Complete hydrolysis is brought about by treatment with
hot acids. The main products of hydrolysis which have been thus
obtained from various nucleinic acids can be grouped under five
headings : —

1. Phosphoric acid.

2. Lsevulinic acid, a substance formed by the oxidation of
carbohydrates, and indicating the presence of a hexose (the nucleic
acids from plants, yeast foTr instance, contain a pentose).

3. Derivatives of purine —

(1) N= CH (6)

I I

(2) HC C (5)— NH (7k

II II /CH (8)

(3) N-C (4)— NH (9r

namely —

Adenine = 6-Aminopurine ; Hypoxan thine = 6-Oxypuvine ;
Guanine = 2 Amino-6 Oxypurine ; Xanthine = 2-6 Dioxypurine.

Of these only adenine and guanine are present as such in
the nucleic acid molecule, while hypoxanthine and xanthine are

1 Miescher, loc. cit., "Die Spermatozoen einiger Wirbelthiere," Histochemische
A rbeiten ; Mathews, loc. cit.

3 For a complete account of the chemistry of nucleic acid see Jones, " Nucleic
Acids," in the series Monographs on Biochemistry, 2nd Edition, London, 1920.

308 THE PHYSIOLOGY OF REPRODUCTION

formed from them in the process of hydrolysis by a secondary
reaction.

4. Derivatives of pyrimidine —

(1) N=CH (6)

I I

(2) HC CH (5)

(3) N— CH (4)

(2) HC CH (5)

UH
namely—

Cytosine = 6 Aiuino-2 Oxypyrimidine ;

Uracil = 2-6-Dioxypyrimidine ;
Thymine = 5 Methyl-2-6 Dioxypyrimidine (Methyl-Uracil).

Of these cytosine and thymine are present as such in the nucleic
acids obtained from animals, while uracil is formed from cytosine by
a secondary reaction in the process of the splitting up of the nucleic
acid.

In the nucleic acids of plant origin uracil is bound iip as such and
takes the place of thymine. So far as our present knowledge goes
only two nucleic acids — or groups of nucleic acids — occur in nature ;
one obtainable from the nuclei of animal cells, the other from the
nuclei of plant cells. The difference consists, as has just been stated,
in the presence of a hexose and of thymine in the animal nucleic
acid, while the plant nucleic acid contains in their stead a pentose
and uracil. It is, however, significant that the only two exceptions
have so far been found in certain nucleic acids obtained from the
generative organs. The nucleic acid obtained from the eggs of a fish
(Gadus aigle/inus) contains uracil and a pentose but no thymine and
no hexose.1 And while nucleic acid prepared from ripe spermatozoa
does not contain pentoses, these substances are stated to be present
in the nucleic acid of the testis of the bull,2 which represents the
acid constituent of the nuclei of the sexual element in the various
stages of their development. Since the statement of the presence
of a pentose in the nucleic acid from the testis of the bull is
based only on the preparation of an osazone, further investigation
on this point and analytical data are necessary before it can be
accepted.

The origin of the purine and pyrimidiue derivatives which form
part of the nucleic acid molecule is as yet obscure. In experiments
on the developing ovum it has been shown (see p. 282) that the
living cell has the power of synthesising these substances.

This has been confirmed by experiments on Mammals by various

1 Levene and Mandel, " Uber die Nukleinkorper des Eies des Schellfisches
(Gadus ceglefoius)," Zeitsch. f. physiol. Chem., vol. xlix., 1906.

-' Steudel, "Cber die Kohlenhydratgruppe in der Nukleins(aure," Zeitsch. f.
physiol. Chem., .vol. Ivi., 1908.

BIOCHEMISTRY OF THE SEXUAL ORGANS 309

observers.1 The nature of the substances which supply the material
for the formation of the purine bodies remained unknown until
Ackroyd and Hopkins 2 found that in the urine of rats the amount of
allantoin, which is derived from uric acid, was greatly diminished
when the diet of these animals was so constituted as to be free from
the diainino acids histidine and arginine. They conclude, therefore,
that these constituents of the protein molecule represent specifically
the raw material for the synthesis of the purine bodies.

The structure of nucleic acid is almost completely established.
As has been stated above, animal nucleic acid , contains phosphoric
acid, a hexose and four nitrogenous ring compounds. These are
arranged in such a way in the nucleic acid molecule that a carbo-
hydrate group links a phosphoric acid group with either a purine or
a pyrimidine group. Such a compound is called a nudeotide. As an
example, guanine-nucleotide may be given thus : phosphoric acid —
hexose — guanine. In nucleic acid four such mononucleotides are
bound together, so that the structure of animal nucleic acid may be
represented thus : —

* Phosphoric acid — hexose — guanine.

Phosphoric acid — hexose-r— thymine.
Phosphoric acid — hexose — cytosine.

Phosphoric acid — hexose — adenine.

In other words, the "skeleton" of the nucleic acid molecule is
formed by four molecules of phosphoric acid combined with four
molecules of a sugar:3 a tetraglyco-phosphoric acid, similar to the
glycerophosphoric acid which forms the "skeleton" of phosphorised
fats. In the nucleic acid molecule this glycophosphoric acid is
combined with four different nitrogenous substances, of which two are
pyrimidine derivatives and two are purine derivatives.

1 Burian and Schur, " Uber Nukleinbildung im Saugethierorganismus,"
Zeitsck. f. physiol. Chem., vol. xxiii., 1897. Osborne and Mendel, " Beobachtungen
iiber Wachstum bei Futterungsversuchen mit isolierten Nahrungssubstanzen,"
Zeitsck. f. physiol. Chem., vol. Ixxx., 1912. Benedict, "Uric Acid in its Relation
to Metabolism," Jour. Lab. and Clin. Medicine, vol. ii., 1916.

2 Ackroyd and Hopkins, "Feeding Experiments with Deficiencies in- the
Ammo- Acid Supply : Histidine and Arginine as possible Precursors of Purines,"
Biochem. Jour., vol. x., 1916.

3 The sodium-salt of a tetraphosphoric acid can be prepared by fusing
together the sodium metaphosphate and pyrophosphate (Kraut and Uelsmann,
Liebig's Annalen, vol. cxviii., 1861). The organic derivatives of this base have
not yet been studied.

310 THE PHYSIOLOGY OF REPRODUCTION

Reference has already been made to the fact that in the salmon
the material for the growth of the testis is supplied by the muscle
undergoing atrophy. The analogy existing between the glyco-
phosphoric acid which forms the " skeleton " of the nucleic acid, and
the glycerophosphoric acid which forms the skeleton of phosphorised
fats, suggests that the glycerophosphoric acid present in the muscle
as phosphorised fat furnishes the material from which the glycophos-
phoric acid bound up in the testis as the nucleic acid is formed. This
view is supported by the fact that, during the period of the growth
'of the testis, the blood of the salmon is exceptionally rich in phosphorised
fats, and that the tail of the spermatozoon is also very rich in
phosphorised fats. It would appear that ' these substances, after
having been transported to the testis, are there built up partly into
the nucleus of the spermatozoon, while part remains accumulated in
the tail of the spermatozoon as reserve material.

Owing to their characteristic histochemical reactions the fate of the
lipoids in the testis can be followed to a certain extent. In the active
adult testis the interstitial cells are loaded with globules of lipoid
material. It is double-refracting in addition to staining with Sudan
and with osmic acid after bichromate, and is therefore not ordinary
neutral fat, but a mixture of ordinary fat with lipoids, such as lecithin
and cholesterin, similar to the mixture which is present in the adrenal
cortex or the corpus luteum. Similar globules are present also in
small amounts in the seminiferous tubules, where they show a regular
distribution in the spermatogonia, and more especially in the Sertoli
cells,1 to which the spermatids are attached while undergoing
differentiation into .spermatozoa and from which they presumably
absorb the lipoids. From observations on human material Mott 2 has
drawn the significant conclusion that the interstitial cells are free from
lipoids until puberty, when active sperniatogenesis begins. The
importance of a normal metabolism of lipoids is further demonstrated
by the correlation which exists between abnormalities in the adrenal
cortex and the function of the testis. Hypertrophy of the adrenal
cortex is associated with sexual precocity. Conversely Mott has
found in cases of dementia praecox an atrophic adrenal cortex poor in
lipoids and associated with it regressive atrophy of the testis. The
writer 3 has found a similar correlation in the condition produced by
feeding animals on a diet free from vitamins. This leads to disturbances
in the distribution of the cortical lipoid of the adrenal and there is
also atrophy of the seminiferous tubules of the testis.

1 Schafer, Text-book of Microscopic Anatomy, Longmans, Green & Co., 1912,
p. 622.

2 Mott, " Normal and Morbid Conditions of the Testes from Birth to Old
Age in one hundred Hospital and Asylum Cases," Brit. Me<l. Jovr., 1919.

3 Cramer, Unpublished observations.

BIOCHEMISTRY OF THE SEXUAL ORGANS 311

The observations of Miescher l allowed of a quantitative estimation
of the amount of nucleic acid and protamine present in the head of
the spermatozoa of the salmon after the fat had been removed. 60'5
per cent, of nucleic acid was found to be combined with 35'5 per cent,
of salmine, so that 96 per cent, of the head of the spermatozoon
consists of protamine nucleate. This protamine nucleate is, however,
not of the same nature in different parts of the head, the outer layer
containing a basic nucleate rich in protamine, while the inner portion
is composed of an acid nucleate poorer in protamine.

The same quantitative relations have been shown to exist in the
spermatozoa of the herring,2 and similar conditions may be assumed
to exist in the case of the spermatozoa of other animals, the only
difference being the nature of the protein molecule which is combined
with the nucleic acid. It is a protamine or a histoiie in the case of
the fishes, but a typical protein in the case of the higher Vertebrates.3

Of the remaining four per cent, about one-half consists of inorganic
salts, mainly calcium phosphate and calcium carbonate, while the
other half consists of an organic substance, the composition of which
has not yet been recognised. The most important fact known about
it is that it contains 0*12 per cent, iron in organic combination.
The presence of iron can be recognised only after incineration. To
this iron - containing organic substance Burrian 4 applies the name
" Karyogen," a word originally coined by Miescher to designate the
residue which he obtained after what Schmiedeberg's 5 calculations
showed to be an incomplete extraction of the protamine and nucleic
acid from the heads of the spermatozoa of the salmon. Since
Macallum6 was able to demonstrate by means of a microchemical
method the presence of iron in the chromatin of the nuclei of cells,
it seems possible that the " Karyogen " represents the chromatin
substance of the spermatozoon.

The chemical analysis of the spermatozoon is therefore complete.
It shows that the tail is very rich in. phosphorised fats which are
accompanied by cholesterin, fats, and a typical protein. The head
consists almost entirely (ninety-six per cent.) of a substance — a

1 Miescher, hutochemischc Arbeiten.

2 Bendixand Elstein, "Uberden Pentosengehalt tierischer und menschlicher
Organe," Zeitsch.f. allgcm. Physiologic, vol. ii., 1902.

3 Mathews, "Zur Chemie der Spermatozoon," Zeitsch. f. physiol. Chem.,
vol. xxiii., 1897.

4 Burrian, Ergebnisse der Physiologic, vol. v., 1906.

5 Miescher, " Physiologisch-chemische Untersuchungen iiber die Lachsmilch,
nach den hinterlassenen Aufzeichnungen u. Versuchsprotokollen des Autors
bearbeitet u. herausgegeben von O. Schmiedeberg," Arch. f. experiinentclle
Pathologic u. Pharmakologie, vol. xxxvii., 1896, and in Histochcmische v.. Physio-
logische Arbeiten von Miescher.

6 Macallum, " On the Demonstration of the Presence of Iron in Chromatin
by Microchemical Methods," Proc. Roy. Soc., vol. 1., 1892.

312 THE PHYSIOLOGY OF REPRODUCTION

micleoprotein — one component of which is constant for the different
species and classes — the nucleic acid. The other more or less basic
component varies widely for the different classes of Vertebrates, and
shows minor variations for the different species in any one class.
Besides this nucleoprotein, another organic substance, containing
iron in organic combination, is present in very small amounts.

It is perhaps natural that attempts should have been made t<>
associate these different substances with the functions of the sper-
matozoon. But such speculations are hardly justifiable until our
knowledge of the nucleus of the ovum is as complete as it is in the
cases of the male nucleus. At present we know practically nothing
of the chemical composition of the nucleus of the ovum. Nor is
it likely — and Miescher himself clearly recognised this — that the
intricate processes which are connected with fertilisation and heredity
are directly dependent upon such crude chemical facts as the per-
centage of arginine or serine, or the composition of nucleic acid.

We are on safer ground when we consider the head of the
spermatozoon simply as a typical nucleus, and when we draw
deductions from the chemical composition of the nuclear material of
the spermatozoon, as to the functions of the nucleus generally.

It is a very suggestive fact that the nucleus — that is to say,
that part of the cell which is pre-eminently concerned in the new
formation of living material — is distinguished by the presence of
pyrimidine and purine derivatives, substances rich in nitrogen, which
are arranged in a chain of alternating C and N atoms.1 In the
spermatozoon, where the nuclear function finds its most pronounced
expression, we find, at least in the case of the fishes, a further concen-
tration of such groups with alternating C and N atoms. For, besides
the pyrimidine and purine derivatives of the nucleic acid part, there
is also present the basic protamine part. As has been explained
above, this part is composed largely of arginine, which, as the formula
given on p. 304 shows, contains the group —

NH2
NH=C— NH— CH2— . . .

These facts suggest that this special arrangement of alternating
C and N atoms is the chemical expression of the specific function
of the nucleus, and that this arrangement plays a special part in
bringing about the chemical processes which lead to growth and to
the new formation of living matter.

In the case of the other organic compound present in every
nucleus, which contains iron in organic combination, the evidence

1 Kossel, "Einige Bemerkungen iiber die Bildung der Protamine iin
Thierkorper," Zeitsch. f. physiol. C/iem., vol. xliv., 1 905.

BIOCHEMISTRY OF THE SEXUAL ORGANS 313

that it plays an active part in the synthetic functions of the nucleus
is even more suggestive. It was shown by Spitzer1 that the
oxidising enzymes which are present in every cell are localised in
the iron-containing constituent of the nucleus, and Loeb concludes
that the nucleus must be regarded as the essential respiratory or
oxidising organ of the cell.2 Oxidation processes are generally
supposed to be necessary only for the transformation of chemical
energy into heat and mechanical work. But they are, according to
Loeb, equally necessary for other more important and more general
vital processes, i.e. growth and cell division, which come to a stand-
still in the absence of oxygen. As a rule, cell division follows upon
the synthesis of nuclear material, especially chromatin material,
from the protoplasm of the cell. If we accept Schmiedeberg's 3 view
that in the living cell synthetic processes occur through the
intervention of oxygen, we may conclude that the oxygen which
is required for the process of cell division is needed for the
synthesis of nuclear material, and, since it is the iron-containing
organic compound present in the nucleus which lias the power of
bringing about oxidations, it would follow that the synthetic functions
of the nucleus (and hence cell division) are dependent upon this
compound. It must, however, be understood that these considera-
tions are still very hypothetical, and that other biologists4 deny
that the nucleus is the respiratory or oxidising centre of the cell.

Similar observations on the localisation of the intracellular
oxidising processes in the nucleus have been made by Lillie5 and
by Unna.6

THE BIOCHEMISTRY OF FERTILISATION : ARTIFICIAL
1*A RTH EXOGEX ESIS

What is the biochemical significance of the process of fertilisation ?
The answer to that question we owe mainly to the brilliant work of
Jacques Loeb " on artifical parthenogenesis. In 1899 he found,8 as
the result of systematic attempts to induce development in the

1 Spitzer, "Die Bedeutung gewisser Nukleoproteide fur die oxydative
Leistung der Zelle," PfliigeSs Arch., vol. Ixvii., 1897.

- Loeb, Dynamics of Living If after, New York, 1906.

3 Schmiedeberg, "Uber Oxydationen und Synthesen im Thierkorper," Archiv
f. e.i'penmentelle Pathologie v. Pkarmalcologie, vol. xiv., 1881.

* See Verworn, Allgemeine Physiologic, 1909; also Pighini, "Uber die
Indophenyloxydase im Nervensystem," Biochem. Zeitsch., vol. xlii., 1912.

5 Lillie (F.), "On the Oxidative Properties of the Cell Nucleus," Amer. Jour,
of Physio!., vol. vii., 1902.

6 Unna and Golodetz, " Biocheuiie der Haut," in Oppenheinier's Hand-bitch
<ler Biochemie, Erganzungsband, Jena, Gustav Fischer, 1913.

7 Loeb (Jacques), Artificial Parthenogenesis and Fertilisation, University of
Chicago Press, Chicago, 1913.

8 Loeb (J.), "On the Artificial Production of Normal Larvae 'from the Un-
fertilised Eggs of the Sea-Urchin," Amei: Jour, of Physiol., vol. hi., 1900.

314 THE PHYSIOLOGY OF REPRODUCTION

unfertilised eggs of a sea-urchin (Arbacia), that such eggs, when
exposed for two hours to a mixture of equal parts of sea- water and
of a 10/8 m. MgCl.2 solution and then replaced in normal sea- water,
developed into swimming larv;e. The effect of adding the MgCL,
solution was to raise the osmotic pressure considerably, and further
experiments showed that this increase of osmotic pressure was the
essential factor in this original method of artificial parthenogenesis.
It had thus become possible to replace the mysterious complex
" living spermatozoon " by well-known physico-chemical agencies. He
found subsequently that a great variety of different agencies are able
to induce parthenogenesis. From a wealth of experimental data Loeb
has evolved a theory which may be summarised as follows : The
development of the mature ovum is dependent upon two processes.
It is initiated by a cytolysis affecting the periphery of the cell.
Morphologically this process is represented by the formation of a
fertilisation membrane, which is really the essential step in the
activation of development. Membrane formation can be induced
by any agent having a cytolytic action : fatty acids, saponin and
similar substances, lipoid solvents, bases, rise in temperature, certain
inorganic salts, e.g. BaCl2, CaCl2, KCNS, and lastly, the blood-serum
or cell extracts of certain species, but foreign to the species to which
the ovum belongs.

The next question is : Why is a cytolysis necessary to initiate
the development of the egg? The answer is to be found in the
observations of Warburg,1 that the oxygen consumption of the sea-
urchin egg shows a sudden increase after fertilisation to seven times
that of the unfertilised egg. Mechanical disintegration of the
unfertilised egg, even injury to the cortical layer, results in a similar
increase in oxygen consumption. These results were confirmed by
Loeb and Wasteneys for the eggs of Strongylocentrotus purpuratus.
They also found an increased oxygen consumption after the action of
cytolytic agents and after the formation of a fertilisation membrane.
It would follow that the contents of the unfertilised egg are in
a highly oxidisable condition, but that the cortical layer of such an
egg does not present conditions favourable for the oxidation of its
contents to take place. Cytolysis removes an obstacle so that
the oxidations become possible. Loeb suggests that by breaking
down the peripheral lipoid emulsion, certain substances which were
previously solid are liquefied and allowed to diffuse into the
egg, where they start or accelerate the chemical processes under-
lying development. The oxygen consumption increases before cell

1 Warburg, " Beitrage zur Physiologic der Zelle, insbesondere iiber die
Oxydations gtfschwindigkeit in Zellen," Ergebnisse der Physivlogie, 1914, vol. xiv. ;
see also Zeitsch. f. physiol. Chem., vol. Ivii., 1908 ; vol. lx., 1909 ; vol. Ixvi., 1910.

BIOCHEMISTRY OF THE SEXUAL ORGANS 315

division sets in., and oxygen consumption and development are to a
large extent independent of each other. Development is therefore
not the cause of the increased oxygen consumption. On the con-
trary, the increased oxygen consumption is the cause of develop-
ment, and fertilisation is the method by which this increased oxygen
consumption is induced. This conception has received strong con-
firmation by the recent work of Shearer.1 On bringing together
the eggs and the sperm of Echinus microtubercnlatus there is at once
during the first minute an enormous increase in the oxygen con-
sumption. In fact, this increase during the first minute is much
greater than that observed at any subsequent period. The significant
fact is that this increase occurs before the spermatozoa have pene-
trated the cell membrane. The increased oxygen consumption must
therefore be due to a change at the extreme periphery of the egg.
Shearer suggests that the cortical lipoid layer contains traces of
iron. As we have seen (see p. 313) traces of iron may act as a
catalyst: for instance, they greatly increase the oxygen absorption
by emulsions of lecithin.2 In the unfertilised egg the iron is present
in the cortical layer in an inactive condition, and is set free by the
alteration in the cortical layer induced by the spermatozoon.

If the initial cytolysis is allowed to proceed unchecked the eggs,
although they begin to divide, eventually undergo complete cytolysis
and die. A second corrective process is necessary to save the life
of the cell. Experimentally this second corrective life-saving process
consists either in stopping oxidation altogether by immersing the
eggs in a potassium cyanide solution or by depriving them of oxygen,
or by placing the eggs for a short time in a hypertonic salt solution
containing oxygen. The eggs then develop in the same way as if
they had been fertilised by a spermatozoon. They develop into
larvae, and such larva? can, with the necessary care, be reared to
sexual maturity. Delage has succeeded in doing so in the case of
the sea-urchin. Loeb and Bancroft raised a parthenogenetic frog
through metamorphosis and found that its sex glands contained eggs.

How this second process, which Loeb terms the "corrective
factor," operates is not very clear. One can only conclude that it
is not only necessary that the metabolism of the mature ovum should
be stimulated and reach a certain optimum, but the processes thus
initiated by the formation of a fertilisation membrane must be
properly co-ordinated. Otherwise the entire developmental process
may go astray.

If it be admitted that artificial parthenogenesis reproduces the

1 Shearer, " On the Oxidation Processes of the Echinoderm Egg during
Fertilisation," Proc. Roy. 8oc., B., vol. xciii., 1921. See above, pp. 186-197.

2 Thunberg, loc. cit. See also Warburg and Meyerhof, Zeitzch. f. p/tysiof.
Chem., 1913, vol. Ixxxv.

316 THE PHYSIOLOGY OF REPRODUCTION

conditions governing fertilisation by a spermatozoon, then it follows
that a spermatozoon should contain two substances, namely, a
cytolysin and a substance inhibiting the initial cytolysis. The
presence in the spermatozoon of a cytolysin can indeed be proved.
Extracts of the testis of a cock, or the dead semen (killed by heating)
of a starfish or a mollusc, will induce the initial process of cytolysis
in the eggs of a sea-urchin. The dead semen of a sea-urchin,
however, is quite inactive against the eggs of a sea-urchin. The
observations of Pieri,1 of Dubois,2 and of Winkler,3 who claimed to
have extracted from the spermatozoa of various invertebrates ferments
which induced segmentation of the mature ovum of the same
specieSi were proved to be due to fallacies by Gies 4 and by Cremer.5
The fact is, as Loeb showed, that the extracts must Ije prepared from
the spermatozoa belonging to a foreign species. This apparently
paradoxical phenomenon is in agreement with our knowledge of
the actions of cytolysins generally. The cytolysins present normally
in the serum or the cells of one animal are always inactive against
the cells of animals of the same species, and act only against cells of
animals of a different species. The explanation of this fact is to be
found, according to Loeb, in the diminished permeability of the cells
of one species towards the cytolysins produced by the cells of animals
of the same species, the so-called auto-cytolysins.

Similarly the ovum of an animal is not permeable to the
cytolysins contained in the spermatozoon of an animal of the same
species. In order to bring about the development of the mature
ovum the auto-cytolysin must be carried bodily into the egg. And
that is the function of the motile spermatozoon.

This bold conception has received a striking though unintentional
confirmation by the observations of Bataillon. He succeeded in 1910 in
inducing parthenogenesis in frogs' eggs by simply pricking them with
a needle, provided, as he found afterwards, that the needle carried
with it a trace of the blood. He believes that it is the leucocytes
which are introduced by the needle which cause the development.
A few years previously Guyer in 1907 had obtained similar positive
results by injecting frogs' eggs with the lymph or the blood from
another frog.

1 Fieri, " Un nouveau Ferment soluble : 1'Ovulase," A rchives de Zodogie
E.vperimentale et Genwate, vol. xxix., 1899.

2 Dubois, " Sur la Spermase et 1'Ovulase," Comptes Rendus de la Soc. de
Riol., vol Hi., 1900.

3 Winkler (EL), " Uber die Furchung unbefruchteter Eier unter der
Einwirkung von Extraktivstoffen a. d. Spermata," Nachrichten der kgl. Gesell-
schaft der Wissenschaften zu Giittingen, Mathemat.-Phys. Klasse, 1900.

* Gies, " Do Spermatozoa contain an Enzyme having the Power of Causing
Development of Mature Ova?" Amer. Jour, of P/iysioL, vol. vi., 1901.
6 Quoted from Loeb, Dynamics of Living Matter.

BIOCHEMISTRY OF THE SEXUAL ORGANS 317

Loeb's work has proved of great heuristic value and has attracted
many workers to this fascinating field of cytochemistry. A very
interesting historical account of the whole subject together with a
very full bibliography is given by F. R. Lillie in his book, " Problems
of Fertilisation." l He criticises some of Loeb's conclusions and
contributes a new hypothesis. It is based mainly on the observation
that mature eggs of Arbacia and certain other invertebrates, when
suspended in sea-water, secrete a substance which agglutinates the
spermatozoa of the same species. It is a specific reaction and is
given only by mature eggs, and neither by fertilised eggs nor
by immature eggs. The jelly membrane of the eggs is saturated
with this substance, which Lillie calls " fertilisin." It has the
physical characters of a colloid, being nou-dialysable, and is very
heat resistant ; when allowed to act on spermatozoa it disappears
from the solution if not present in excess. It possesses a considerable
degree of specificity if tested against spermatozoa belonging to
different species. Its action on the spermatozoa is to agglutinate the
heads of the spermatozoa which swell, while the tails remain
unaffected. The adhesive property which the sperm develops under
these circumstances binds the egg to the sperm, and is evidence of
an intimate chemical combination of sperm- and egg-constituents
beginning at the very moment of union. The presence of the
agglutinating substance is necessary for the activation of development
in the egg of the sea-urchin, and Lillie suggests that as the result of
the interaction of this substance with the head of the spermatozoa a
substance is formed or released which activates the egg. " The
spermatozoon is conceived, by means of a substance which it bears
and which enters into union with the fertilisin of the egg, to release
the activity of this substance within the egg."

Other workers look upon physical changes occurring in the
colloids of the ovum as the essential processes causing development.
Thus Yves Delage2 looks upon the membrane formation which
precedes segmentation of the egg as a coagulation or gelation. This
is followed by disappearance of the nuclear membrane which he
interprets as a liquefaction or degelation. He therefore ^devised a
very successful method of artificial parthenogenesis in which the
application of a coagulative agent, namely tannic acid, is followed by
treatment with a liquefying agent, namely ammonia.

Wolfgang Ostwald3 has determined the amounts of oxidising

1 Lillie (F.), Problems of Fertilisation, University of Chicago Press, 1919.

• Delage and Goldsmith, La Parthenogenese naturelle et experimental^ Paris,
E. Flammarion, 1913.

3 Wolfgang Ostwald, " CTber das Vorkommen von oxydativen Fermenten in
den reifen Geschlechtszellen von Amphibien und liber die Rolle dieser Fermente
bei den Vorgangen der Entwicklungserregung," Biochem. Zeitsch., vol. vi., 1907.

318 THE PHYSIOLOGY OF REPRODUCTION

ferments present in the ovaries and testes of toads, frogs, and newts.
The watery extracts of these organs had the power of decomposing
hydrogen peroxide with the formation of water and oxygen, and of
oxidising guaiaconic acid to guaiacum blue, so that a blue colour
appeared when these extracts were added to an emulsion of guaiac
resin. These reactions indicate the presence of a catalase and of a
peroxidase in the extracts of the sexual glands. Such ferments are
present in many, if not all, organs and tissue fluids, but a special
significance is attributed by Ostwald to their presence in the ova
and spermatozoa, because he found the spermatozoa to contain
more catalase and more peroxidase than the ova, and because
the activity of these ferments — especially the peroxidase — is
increased when the extracts of ova are mixed with the extracts
of spermatozoa.

The development of the ovum after fertilisation is, according to
Ostwald, due to this activation of the oxidising ferments inducing a
chemical synthesis of nuclein substances and leading to the formation
of the astrosphere. According to the view, of Fischer and Ostwald,1
which is, however, not accepted by other workers,2 the formation of
the astrosphere initiates cell-division, and therefore the development
of the egg.

The investigations on artificial parthenogenesis show that it is
possible to replace the developmental function of the spermatozoon
by physico-chemical means. But the spermatozoon has also the
hereditary function of transmitting the paternal characters to the
developing embryo by fusing its nuclear material with that of
the ovum. One must distinguish, therefore, clearly between these
two functions of the spermatozoon. There is evidence that these
two functions depend upon different materials in the spermatozoon
and that even when an ovum is fertilised by a spermatozoon only
one of these two functions may operate, namely the developmental
one, while the hereditary function remains inoperative. Loeb
succeeded in inducing experimental hybridisation between two widely
different species, the egg of a sea-urchin and the sperm of a starfish,
by placing them in slightly alkaline sea-water. The plutei which
developed were in every point identical with the pure breed of the
sea-urchin (Strongylocentrotus purpvsratus). Other workers have
obtained similar results in other animals. A very striking case is
that observed by Hertwig and based on the fact that exposure of
spermatozoa to radium damages them. The damage can be graded
in such a way that the spermatozoon can still enter the egg, but its

1 Fischer and Ostwald, " Zur Physikalisch-Chemischen Theorie der Be-
fruchtung," Pfluge^s Arch., vol. cvi., 1905.

2 See, for instance, Burrian, loc. cit.

BIOCHEMISTRY OF THE SEXUAL ORGANS 319

nucleus is no longer able to fuse with the egg nucleus. The eggs
then develop into larvae. Other experiments on hybridisation by
various authors have shown that under certain conditions develop-
ment may be initiated by spermatozoa belonging to a different species
without the occurrence of a fusion between the sperm nucleus and
the egg nucleus. The resulting larvae are then purely maternal and
have half the number of chromosomes. In other words : it is possible
to induce parthenogenesis by the spermatozoon.

CHAPTER IX

THE TESTICLE AND THE OVARY AS ORGANS
OF INTERNAL SECRETION

"Da muss sich manches Rathsel Ib'sen,
Doch manches Rathsel kniipft sich auch."

— GOETHE.

THE principal evidence supporting the theory .that the ovary and
testicle are organs of internal secretion is derived from the experi-
mental study of the effects produced, first, by removing these
organs, and, secondly, by transplanting them to abnormal positions
in the body. Experiments of such a kind clearly demonstrate the
influence of the ovary and testicle upon the growth and development
of the other generative organs, and upon many of the secondary
sexual characters. They indicate, moreover, that the nature of this
influence is chemical rather than nervous. Certain further evidence,
which is less satisfactory in character, has been obtained from
experiments on the injection of ovarian and testicular extracts.1

THE CORRELATION BETWEEN THE TESTIS AND THE
OTHER MALE ORGANS AND CHARACTERS

It has already been recorded (p. 251) that the removal of the
testes in adult life brings about a gradual atrophy of the prostate
gland. It has also been shown that this operation, if performed
prior to puberty, prevents the development of the prostate, whereas
division of the vas deferens and the abolition of sperm production
have no arresting influence.2 One-sided castration produces no effect,
the retention of a single testis being sufficient to maintain the
functional activity of both prostate glands. Similarly it has been
stated that Cowper's glands are probably dependent upon testicular
influence for their growth and activity (p. 252).

More remarkable is the close correlation that exists between the

1 For general accounts and references to literature see Harms, ExperimenteUe
Untersuchungen fiber die Inner e Sekretion der Keimdriisen, Jena, 1914 ; Lipschiitz,
Die Pubertatsdriise und ihre Wirkungen, Berne, 1919 ; and Gley, Les Secretions
Internes, Paris, 1914.

2 Wallace (C.), Prostatic Enlargement, London, 1907. It is shown also that
vasotomy has no influence on the growth and activity of the prostate.

THE TESTICLE AND THE OVARY 321

testes and the secondary sexual characters of the male — that is to
say, those characters which are found only in the male sex, but are
not directly connected with the organs of generation.

Thus, it is notorious that castration before puberty in man
prevents the growth of hair on the face, arrests the development
of the male chest and pelvis, and preserves the high-pitched voice
of boyhood by hindering the growth of the larynx, while at the same
time it exercises a marked influence over the mental characteristics.1
It is equally well known that at the time of puberty, when the testes
begin to assume their functional activity, there is a corresponding
development of the secondary sexual characters, both in man and
in a large number of animals. This correlation appears to be still
closer in those animals in which the increased testicular activity
that takes place in the breeding season is associated with a periodic
development of other sexual characters. Thus, in the male elephant
the glands on the side of the face emit a musky secretion
during nit.

Darwin,2 in elaborating his theory of sexual selection, collected
together numerous examples of secondary sexual differences occurring
in animals of various kinds. Cunningham, in a work upon " Sexual
Dimorphism," has cited a number of further cases,3 in many of which
the structural peculiarities in question are shown to be closely
correlated with the essential organs of reproduction.

The effects of castration in the stag, for example, are discussed
at some length by Cunningham, Morgan,4 and other writers. If the
testes are removed in quite immature animals the antlers never
develop, even the knobs failing to make an appearance. If castration
is performed in stags whose antlers have just commenced to develop,
these remain covered by skin, forming the so-called peruke antlers,
which are not shed or renewed. If the operation is carried out after

1 According to Hikmet and Kegnault (" Les Eunuques de Constantinople,"
EM. et Mem. de la Soc. d'Anthropologie de Paris, vol. ii., 5th series, 1906), the
eunuchs of Constantinople have the following mental characteristics :— They
are avaricious, illogical, obstinate (i.e. cannot change their ideas), have no
judgment, accept information without proof ; are not cruel, but fond of children
and animals ; are faithful in their affections, but have no courage ; their mental
activity is very slight, and they are extremely fanatical. Senility is premature,
but the teeth are kept solid and white. For skeletal differences in eunuchs,
see below, p. 323. See also Kanimerer, "Ursprung der Geschlechtsunterschiede,"
Fortschr. natunviss. Forschung von Abderhalden, 1912 ; and Hirschfeld, Sexiude-
Pathologie, Bonn, 1917.

2 Darwin, The Descent of Man, Popular Edition, London.

3 Cunningham (J. T.), Se.vual Dimorphism in the Animal Kingdom, London,
1900 ; "The Heredity of Secondary Sexual Characters in Relation to Hormones,"
Arch. f. Entwick.-Mech., vol. xxvi., 1908 ; Hormones and Heredity, London, 192L
See also Hegar, Korrelationem der Keimdriisen und Geschlechtsbestimvming, 1893 ;
and Sellheim, " Zur Lehre von den sekundaren Geschlechtscharakteren," Beitrage
zu Geburtsh. u. Gyniik., vol. L, 1898.

4 Morgan, Experimental Zoology, New York, 1907.

322 THE PHYSIOLOGY OF REPRODUCTION

the complete development of the antlers, these are shed prematurely
and are replaced in the next season by incomplete antlers with a
tendency towards peruke formation, and these, on being thrown off,
are not renewed. Partial castration in the immature stag is said t<>
result in a weaker horn formation ; but the effect is general, and
shows no restriction to the side on which the testis is wanting.1

The results of castration in the fallow deer have been investigated
by Fowler,2 who summarises his results under five headings :
(1) Complete castration at birth limits the horn formation to the
development of single dugs ; (2) Castration in mature life tends to
produce asymmetry in the growtli of the horns ; (8) The antlers
of castrated deer are often shed prematurely if the operation is
performed after they have lost the velvet, but antlers which have
grown after castration may be retained for over two years ; (4)
Incomplete castration shortly after birth is followed by a weak
development of the antlers, which are otherwise normal; (5) One-
sided castration may result in the abnormal or incomplete develop-
ment of one antler, the other antler being nearly normal. The last
point would seem to require confirmation.3

In the prong-buck (Antilocapra americana), which is the only
hollow-horned Kuininant that periodically sheds its horns, the effects
of castration are also quite distinct. The horns, instead of rising
vertically as in normal individuals, curve forwards from the roots,
and then bend downwards and backwards so as to terminate in
incurved points in the close vicinity of the eyes. The anterior tine
is almost completely suppressed. The horn-sheath is never shed,
and as a consequence a composite sheath is developed, and this
seems to go on growing as long as new sheaths are formed from the
horn-core.4

It is interesting to note that in the eland, in which both sexes
possess horns, the development of these structures is not appreciably
affected by castration. A similar statement may be made about some
horned cattle, in which (in common with other cattle) castration in

1 These statements are based chiefly-upon the results of Caton's experiments
with Wapiti and Canadian deer (Caton, Antelope and Deer of America,
2nd Edition, New York, 1881. See also Holdich, "Exhibition of Antlers of
Deer showing Arrest of Development due to Castration," Proc. Zool. Soc.,
1905). Some further examples of sexual correlation are given in Chapter I. of
this work. (See Morgan, loc. cit.) Professor Seligman informs me that stags
which fail to grow antlers (i.e. occasional " sports ") have well-developed testicles.

2 Fowler, "Notes on some Specimens of Antlers of the Fallow Deer, etc.,"
Proc. Zool. Soc., 1894.

3 MacEwen (The Growth and Shedding of the Antlers of the JJeer, Glasgow, 1920)
refers to another case of one-sided castration being followed by asymmetrical
horn growth.

4 Pocock, "The Effects of Castration on the Horns of the Prong-buck,"
Proc. Zool. Soc., 1905. It is to be noted that horns are occasionally pi'esent
in the female prong-buck.

THE TESTICLE AND THE OVARY

323

early life produces changes in the general proportions of the
body.

In the sheep, also, castration during iimnaturity brings about
changes in the bodily conformation. Thus, in breeds in which the
males only are horned, the skulls of the wethers may resemble the
females rather than the males.1 This is the case with the Merino
sheep. In the Herdwick it has been shown that not only is the
presence of the testes necessary for the initiation of horn growth, but
for its continuation, the horns ceasing to grow forthwith after
castration and at any stage of horn development. Further, uni-
lateral castration does not inhibit the growth of the horns which
develop symmetrically in the normal manner.2

FIG. 76. — Herdwick rani (normal).
(From Marshall and Hammond,
Jour, of Pltysiol.)

FIG. 77. — Herdwick wether (cas-
trated young). (From Marshall
and Hammond, Jour, of Pkysiol.)

Differences in the form of the body have been noted in eunuchs
as well as castrated animals. Thus, the bones of the limbs tend to
be longer than the normal, producing a condition of gigantism. This
is due to an arrest in the ossification of the epiphyses (which is one
of the effects of castration). The same phenomena have been
described in castrated guinea-pigs, oxen, capons, and various animals.3

1 Seligman, " Exhibition of a Skull of a Domestic Sheep which had been
Castrated when Young," Proc. Zool. /fot1., 1906. Changes in conformation as a
result of early castration have also been described in other animals.

2 Marshall, "On the Effects of Castration and Ovariotomy upon Sheep,"
Proc. Roy. Soc.t B., vol. Ixxxv., 1912. Marshall and Hammond, "On the Effects
of Castration on Horn Growth in Sheep," Jour, of Physiol., vol. xlviii., 1914.
In the Merino also castration is known to arrest the growth of the horns of
the ram (Arkell and Davenport, " Horns in Sheep, etc.," Science, vol. xxxv.,
1912).

3 Lannois and Roy, " Des Relations qui existent entre 1'Etat des Glandes
genitales males et le Developpement du Squelette"; and Poncet, "De 1'Influence
de la Castration sur le Developpement du Squelette," C. R. de la Soc. de Biol.,
vol. lv., 1902. See also Pittard, C. R. de I' A cad. des Sciences, vol. cxxxix., 1904,
who gives statistics showing that there is often an increase in size in eunuchs,

324 THE PHYSIOLOGY OF REPRODUCTION

It is well known that caponisation or the removal of the testes in
fowls arrests the development of the comb and some other secondary

FIG. 78. — Herdwick wether cas-
trated when four months old.
The horns are the same length
as they were at the time of
castration. (From Marshalkand
Hammond, Jour, of Physinl.)

FIG. 80. — Herdwick ram lamb
from which one testis was re-
moved four months after birth.
The horns continued to grow
and were symmetrical. (From
Marshall and Hammond, Jour,
of Physiol.}

FIG. 79. — Herdwick wether cas-
trated five months after birth.
The horns ceased to grow after
castration. (From Marshall and
Hammond, Jour, of P/iysiol.)

FIG. 81. — Herdwick wether from
which the testes were removed
four months after birth but the
epididymes retained. The horn
growth ceased after castration.
(From Marshall and Hammond,
Jour, of Physiol.)

male characters which are normally present in the cock. Eecent
experiments upon this subject are described below in dealing with

especially in the legs. For accounts of other anatomical differences in eunuchoid
persons, see Duckworth, Jour, of Anat. and P/iys., vol. xli., 1906, and Tandler
and Gross (Arch. f. Entivick.-Mech., vol. xxvii., 1909). The latter authors discuss
the general effects of castration on the organism. See also Geddes, "Abnormal
Bone Growth in the Absence of Functioning Testicles," Proc. Roy. Soc. Edin.,
vol. xxxi., 1910.

THE TESTICLE AND THE OVARY 325

the results of testicular transplantation or the injection of testicular
extracts. Other instances of the effects of castration are briefly
referred to by Darwin.1

Secondary sexual characters, however, are not always correlated
with the essential organs of reproduction. For example, castration
in the horse does not arrest the development of the withers — the
gelding, in this respect, resembling the stallion rather than the mare,
in which the withers are lower.2 „

In Arthropods the correlation between the secondary sexual
characters and the generative glands appears to be far less close than
it is among Vertebrates. Thus, Oudemans 3 showed that the removal
of the testes from the male caterpillar of Ocneria dispar had no
influence on the development of the secondary male characters, these
being normal. Kellogg4 performed a similar experiment on the
caterpillar of the silkworm moth and obtained a like result. Crampton5
grafted the heads of caterpillars of one sex upon the bodies of
individuals of the opposite sex, and found that the generative organs
had no influence upon the development of the secondary sexual
characters of the transplanted heads. Moreover, Meisenheimer 6
found that in caterpillars artificially made hermaphrodite (by trans-
planting ovaries into males or testes into females) the original males
always developed into butterflies with typical secondary male
characters in spite of the fact that living ovaries were present, while
the original females always developed into normal female butterflies.
The sexual instincts were also unmodified by the presence of the
grafted gonads. With castrated or spayed individuals .into which
gonads of the opposite sex were successfully transplanted the effects
were similar, the somatic characters of the original sex being
unmodified.7 Kegen 8 who removed the gonads from larval crickets

1 Darwin, foe. cit. Sellheim (Beitrage ztir Geburtshiilfe und Gynak:, vol. i.,
1898, and vol. ii., 1899) states that there is an increase in the size of the skull,
pelvis, and leg-bones in castrated cocks. According to Berizowiski (Arch.
Zellforsch., vol. ii., 1911), castration in mice causes elongation and broadening of
the cells of the intestinal epithelium, but this would seem to need confirmation.

2 Wallace, Farm Live- Stock of Great Britain, 4th Edition, London, 1907.
Williams (W. L.) says there are no sexual differences in the bones of the pelvis
of the horse (Veterinary Obstetrics, New York, 1917).

3 Oudemans, "Falter aus Castraten Raupen," Zool. Jahrbticher, vol. xii., 1899.

4 Kellogg, "Influence of the Primary Reproductive Organs on the Secondary
Sexual Characters," Jour, of Exp. Zool., vol. i., 1904.

5 Crampton, "An Experimental Study upon Lepidoptera," Arch. f. Enticick.-
Mechanik, vol. vii., 1898.

6 Meisenheimer, Experimentelle 8tvdien zur Soma- tind Geschlechts-Differ-
enzienmg, Part I., Jena, 1909.

7 Kopec, "Nochmals iiber die Unabhangigkeit der Ausbildung sekundaren
Geschlechtscharaktere von den Gonaden bei Lepidopteren," Zool. A nz., vol. xliii.,
1913. See also Kammererx toe. cit.

8 Regen, " Kastration und ihre Folgerscheinungen bei Grylhis campestris"
Zool. Anz., vols. xxxiv. and xxxv., 1909 and 1910.

326 THE PHYSIOLOGY OF REPRODUCTION

<-n in jiestris), found that tlie castrated males chirped like normal
ones and mated with the females, and the spayed females behaved
like unoperated ones and bored holes in the ground although they
were unable to lay eggs in them.

In spider crabs attacked by Sacculina the gonads disappear, and
in the total absence of the testis secondary sexual characters of the
female type are found in a large percentage of cases ; but this change
in the direction of the opposite sex may set in prior to the complete
disappearance of the testes. The change is manifested in the
appearance of the egg-bearing abdominal sac appendages, which have
no representatives in the male.1 Potts states that in the hermit crab
infected by a similar Peltogaster, the modifications of the male which
occur are of the same type, and are maintained after the atrophy of
the testis, and cannot be necessarily consequent on the presence • •[' a
secretion of the testis.2

In both these cases it would seem that the modifications which
take place are brought about independently by changes in the general
metabolism. This appears to be so also with so-called parasitic
castration in insects, for the gonads are not necessarily affected.

In the male common shore crab it was found that the testis
underwent very little diminution after infection by Sacculina, but
that the male approximated to the female type. The change,
however, was less marked than in the cases referred to above, in
which parasitic castration was almost or quite complete.3

It would appear, therefore, that whereas many of the secondary
sexual characters are closely associated with the presence of the
genital glands, there are others which develop independently of any
influence from the organs of reproduction.

Berthold seems to have been the first to put forward the view
that the testis is an organ of internal secretion which is responsible
for the development of the secondary sexual characters.4 He based
his theory upon the results of testicular transplantation in fowls in

1 Smith (Geoffrey), "Khizocephala, Fauna and Flora of the Gulf of Naples,"
Monograph xxix., Berlin, ] 906.

2 Potts, "The Modification of the Sexual Characters of the Hermit Crab,
caused by the Parasite Petiogaster," Quar. Jour. Micr. Science, vol. 1., 1906 ; and
"Some Phenomena Associated with Parasitism," Para sit ology, vol. ii., 1909.

3 Potts, "Observations on the Changes in the Common Shore Crab caused
by Sacculina," Proc. Camb. Phil. Soc., vol. xv., 1909. Upon recovery from
parasitic castration ova may be formed in what were the testes. This has been
shown by Smith to happen with Inachm. Smith states that the parasite
Sacculina forces the crabs to elaborate a fatty or yolk material similar to that
which the normal female produces when the ovary is ripening. See also Smith's
"Studies in the Experimental Analysis of Sex," (juai: Jour. J/Ar. Science,
vols. Ivi. and Ivii., 1910 and 1911. For the results of experimental or parasitic
castration in other Arthropods and groups of Invertebrates, see Lipschutz, loc. cit.

4 Berthold, "Transplantation der Hoden," Arch. f. Anat. u. PhysioL, vol.
xlii., 1849. '" According to Berman (The. (llmtds regulating Personality, New
York, 1921),the idea was advanced by Bordeu in the eighteenth century.

THE TESTICLE AND THE OVARY 327

which the testes, after removal, were attached to new positions and
still sufficed for the development of the sexual characters. In
attributing this role to the testes, Berthold appears also to have been
the first to assign an endocrine function to any bodily organ, thus
anticipating Claude Bernard and the numerous physiologists who
have succeeded him.

It was not till some years later that Brown-Sequard l elaborated
the theory that the testis exercises an influence upon the general
metabolism through the internal secretion produced by it. He
based his conclusion to a large extent upon the beneficial effects
which he believed to accrue from the administration of testicular
extracts. These extracts were supposed to possess invigorating
properties, and could be usefully employed in cases of deficiency of
testicular substance, or in old age, when the testes lose their
functional activity. It is not unlikely that some of the effects
which Brown-Sequard attributed to the use of the extract were in
reality due to suggestion.

The idea of a connection between testicular influence and
invigoration or rejuvenescence has lately been revived with reference
to the interstitial gland of the testis, and it has been claimed that
successful transplantation of this tissue into the aged has been
followed by beneficial results. Thus, Steinach 2 has described experi-
ments upon rats, which, after reaching a condition of senility and
impotency and with the vesiculie seminales and other accessory male
organs undergoing atrophy, were restored to a state of vigour and
functional activity by the transplantation of interstitial testicular
tissue. Rejuvenescence coiild also be brought about as a result of
vasectomy, an operation which, as described below, results in the
eventual atrophy of the seminiferous tissue, but in the persistence or
even hypertrophy of the interstitial or "puberty gland," and according
to Steiuach the same effects are produced by vasectomy in aged men.
In confirmation of Steinach, Sand 3 records an experiment upon a

1 Brown-Sequard, "Du R61e pliysiologique et therapeutique d'un Suc.extrait
de Testicules," Arch, de Physiol., 1889.

2 Steinach, V&yilngung (lurch experimentdle Neubelebung der Alternden
Pubertatsdriise, Berlin, 1920 (reprinted from Arch.f. Entwicks.-Mech., vol. xlvi.,
1920). According to the penal laws of Indiana (1907), California and
Connecticut (1909), in the United States of America, vasectomy may be carried
out on male criminals in order to prevent them propagating, while at the same
time not impairing their normal masculine vigour. I am indebted to the late
Viscount Bryce, at one time H.M. Ambassador to the United States of America,
for information on this subject (see Sharp, Jour. Amer. Ned. Asxoc., 4th December
1909). If Steinach is correct in believing that increased vigour and prolongation
of life may be a result of vasectomy, the policy of which these laws are the
outcome is one of doubtful wisdom. At any rate some other way of inducing
sterility might be adopted.

3 Sand, " Vasectomie pratiquee chez un Chien, etc.," C. R. de 8oc. de ftiol.,
vol. Ixxxv., 1921.

328 THE PHYSIOLOGY OF REPRODUCTION

dog which showed every sign of senility and decrepitude, but after
the operation of bilateral vasectomy was rejuvenated and restored to
a state of robust vigour.

Voronoff has made a similar claim for the interstitial tissue of the
testis and appears to regard the hormone secreted by this gland as
the veritable "elixir of life." The body is pictured as a battle-
ground in which there is a prolonged struggle between the " primitive
cells" (represented by those of the connective tissue) and the
" specialised cells " which show an intenser metabolic activity, and
senescence indicates the progress of the former, with death as their
complete victory. The internal secretory organs exercise a regulating
influence on the combat, and more especially the interstitial gland,
for the atrophy or loss of this leads to a rapid victory by the
connective tissue cells. The eunuchs of Egypt are cited as evidence
of the truth of this view, and a number of experiments upon animals
are referred to or described, and, as in Steinach's memoir, photographs
and other illustrations are shown representing animals (sheep, goats,
etc.) displaying all the signs of senescence, and then later after a
successful testicular graft had had a sufficient time to work its
rejuvenating influence upon the metabolism.1 A possible fallacy in
all such experiments is the effect of nutritional or any environmental
influence other than that of the graft, and the conclusions reached
must at present be accepted with caution.

Lichtenstern 2 states that the prejudicial effects of castration in
man may be remedied by a successful testicular graft, and this is
believed to be due to the influence of the puberty gland.

Steinach 3 had previously found that in rats in which the testes
were removed and successfully transplanted into the abdominal
cavity the penis and accessory male organs developed normally.

Poehl 4 claims to have prepared from the testis a substance having
the chemical composition represented by the formula C5HUN2. He
believes this substance, which he calls spermine, to be the active
principle of Brown-Sequard's testicular extract, stating that it has
a beneficial influence over the metabolism of the body and acts as
a physiological tonic (see p. 299).

1 Voronoff, Vivre, Paris, 1920. This work contains reprints of histological
papers by Retterer as an Appendix.

2 Lichtenstern, " Behebung von Kastrationsfolge beim Menschen durch
Transplantation von cryptorchen Hoden," Munch, ined. Woch. (19), 1916. See
also Steinach and Lichtenstern, " Umstimmung der Homosexualitat durch
Austausch der Pubertatsdrusen," Munch, med. Woch. (21), 1918. For further
testicular transplantation results in man, see abstracts of papers by Stanley and
Kelker, and others in Endocrinology, vols. i.-iv., 1918-21.

3 Steinach, " Geschlechtstrieb und echt sekundare Geschlechtscharactere,"
Zent. f. Physiol., vol. xxiv., 1910.

4 Poehi, " Weitere Mitteilungen iiber Spermin," Berliner Jclin. Wochenschrift,
1891.

THE TESTICLE AND THE OVARY 329

Zoth,1 and also Pregel,2 state that they have obtained evidence by
ergographic records of the stimulating action of testicular extracts
upon the neuro-muscular apparatus in the human subject. They are
of opinion that the injection of such extracts results in a decrease of
nervous and muscular fatigue, and at the same time diminishes the
subjective fatigue sensations.

The composition and physiological properties of testicular extract
have also been investigated by Dixon,3 who found it to contain
proteins, organic substances unaltered by boiling, and inorganic salts.
Nucleoprotein was especially plentiful. Injection into the circulation
caused a fall of blood pressure due chiefly to cardiac inhibition, but
no very striking or interesting results.

Walker4 appears to be dubious about the efficacy of testicular
medication, stating that the injection of fluid extract into castrated
dogs had no effect in arresting the atrophy of the prostate gland
(of. de Bonis, see Chapter VII., p. 251). It is possible, however,
that the " active principle " of the testicular secretion was destroyed
in the preparation of the extract, and that the constant administra-
tion of fresh testicular substance might have led to a different result.
In these experiments extract of the whole gland seems to have been
used and not of the interstitial gland only.

Bourn and Ancel 5 showed in the horse and other animals that
when the vasa deferentia are ligatured the spermatogenetic tissue of
the testis ceases to be functional and gradually undergoes degeneration,
while the interstitial cells remain unaffected. They pointed out,
further, that those cells have a distinctly glandular appearance, and
that their presence suffices for the development of the secondary sexual
characters. Consequently they drew the conclusion that the testis
is an organ producing an internal secretion which is elaborated by
the interstitial cells and not by the spermatogenic tissue. Copeman,"

1 Zoth, "Zwei ergographische Versuchsreihen tiber die Wirkung orchitischen
Extractes," Pfliiger's Arch., vol. Ixii., 1896.

2 Pregel, "Zwei weitere ergographische Versuchsreihen, etc.," Pfiiigei's
Arch., vol. Ixii., 1896.

3 Dixon, " A Note on the Action of Poehl's Spermine," Jour, of Physiol.,
vol. xxv., 1900; "The Composition and Action of Orchitic Extracts," Jour, of
Physiol,, vol. xxvi., 1901. According to Hervieux, the interstitial gland of the
testis contains a ferment which splits neutral fats, and converts dextrin, maltose,
and glycogen into glucose but has no action on lactose (C. R. de la 3oc. Biol.,
vol. lx., 1906).

4 Walker (G.), "Experimental Injection of Testicular Fluid, etc.," Johns
Hopkins Hospital Bidletin, vol. xi., 1900.

6 Bouin and Ancel, " Recherches sur les Cellules interstitielles du Testicule
des Mammiferes," Arch, de Zool. Exper., vol. i., 4th series, 1903.

0 Copeman's experiments, which were upon the rabbit, were not published,
but were personally communicated to Swale Vincent, and alluded to by him in
a lecture on " Internal Secretion and the Ductless Glands," Lancet, 1st August
1906. See also Copeman, "Experiments on Sex Determination," Proc. Zool,
Soc., 1919.

U A

330 THE PHYSIOLOGY OF REPRODUCTION

as a result of similar experiments, reached an identical conclusion.
Ancel and Bouin stated, further,1 as a result of a series of experiments
upon guinea-pigs, that the subcutaneous injection of extract prepared
from the interstitial tissue of the testis prevented the effects which
castration otherwise would have produced upon the rest of the
generative system and upon the skeleton.2 Their results, therefore,
differ from those of Walker. In another paper Bouin and Ancel3
state that the injection of similarly prepared testicular extract in
guinea-pigs tends to promote growth. In the horse they found that
the development of the interstitial gland substance of the adult
coincided with the first occurrence of spermatogenesis ; but that
there was also a foetal interstitial gland, which disappeared at the
end of gestation, and a slightly developed gland composed of
xanthochrome cells, which was only found in the immature animal.4

Tandler and Gross 5 have described the effects of subjecting the
testes to the influence of the Eontgen rays. They found that in
the roebuck the spermatogenetic tissue is destroyed but the
interstitial tissue is unaffected, and in correlation with this the horns
develop as in the normal male. Leo Loeb6 found that in guinea-
pigs with undescended testes the interstitial cells were present, and
although spermatogenesis 7 did not go on, sexual desire was manifested.
Secondary male characters, however, might be absent, the animal
showing female somatic characters (see p. 346). Whitehead8 from a
study of abnormal testes likewise found that the sexual instinct was
associated with the existence of the interstitial cells. The present
writer9 found as a result of an experimental investigation in the
hedgehog that the growth of the accessory organs (vesicuke, etc.)

1 Bouin and Ancel, "Action de 1'Extrait de Glande interstitielle du Testicule
etc.," G. R. de VAcad. des Sciences, vol. cxlii., 1906.

2 Castration in early life, as already mentioned, is said to lead to a prolonged
retention of the cartilaginous unions between the bones, especially in those of
the limbs.

3 Bouin and Ancel, " Sur 1'Effet des Injections de 1'Extrait de la Glande inter-
stitielle du Testicule sur la Croissance," C. R. de la Soc. de Biol., vol. Ixi., 1906.

4 Bouin and Ancel, "La Glande interstitielle du Testicule chez le Cheval,"
Arch, de Zool. Kvper., vol. iii., 4th series, 1905. According to L6caillon the
interstitial tissue in the mole's testis is functionally active during the breeding
season, when the testis is sixty -four times larger than during the resting period.
("Sur les Cellules interstitielles du Testicule de la Taupe consid6rees en dehors
de la P6riode de Reproduction," C. R. de la Soc. de Biol., vol. Ixvi., 1909.)

5 Tandler and Gross, Die Biologischen Grundlagen der Sekundtiren Geschlechts-
charaktere, Berlin, 1913.

6 Loeb, "Relations between the Interstitial Gland of the Testicle, Semini-
ferous Tubules and the Secondary Sexual Characters," Biol. Bull., 1918.

7 See p. 164, Chapter V.

8 Whitehead, "A Peculiar Case of Cryptorchism, etc.," Anat. Record,
vols. ii. and iii., 1908 and 1909.

9 Marshall, " The Male Generative Cycle in the Hedgehog : with Experi-
ments on the Functional Correlation between the Essential and Accessory
Sexual Organs," Jour, of Physiol., vol. xliii., 1911.

THE TESTICLE AND THE OVARY 331

appeared to be correlated with the seasonal development of the
interstitial tissue and not with the seminiferous tubules. Vasectomy
and one-sided castration did not inhibit the seasonal growth of the
accessory organs (see above, p. 246). Rasmussan has found that in
the woodclmck both spermatogenetic and interstitial tissue increased
rapidly in March and April after hibernation, after which the former
continued to display activity, while the latter began to undergo retro-
gression (April to June) and remained ill-developed throughout the rest
of the year.1 Lecaillon 2 has made similar observations on the mole.

Of very great importance are Steinach's transplantation experi-
ments with rats and guinea-pigs, not only on account of the evidence
they show as to the secretory influence of the gonads, but because
of their bearing on the question of sex-determination. The latter
subject is dealt with in a later chapter. Steinach 3 showed that if
the testes are removed from the normal position and transplanted
under the skin, notwithstanding that their ordinary nerve connections
are non-existent, the copulatory organ, vesicula, and other accessory
male organs develop normally. Since the transplanted testes consist
of interstitial cells only, and these are sufficient to cause the male
characters to develop, Steinach designates this tissue the " puberty
gland." Moreover Steinach found that testes transplanted into a
young female, from which the ovaries had been removed, caused the
clitoris to develop into a penile structure, besides stimulating the
animal's growth and producing manifestations of sexual desire as
in the male. Such individuals he regards as being sexually ^inverted
or masculinised. Steinach carried out converse experiments with
ovarian transplantation which are described below.

Lipschutz 4 has studied the structure of the hypertrophied clitoris
in the guinea-pig after masculinisation by means of a transplanted

1 Basmussan, "Seasonal Changes in the Interstitial Cells, etc.," Amer. Jour,
of Anat., vol. xxii., 1917. "Cyclic Changes in the Interstitial Cells, etc.,"
Endocrinology, vol. ii., 1918.

2 Lecaillon, loc. tit.

3 Steinach, " Untersuchungen zur Vergleichenden Physiologic der Mann-
lichen Geschlechtsorgane," Pfl/iger's Arch., vol. Ivi., 1894 ; " Geschlechtstrieb und
echt Sekundare Geschlechtsmerkmale als Folge der Innersekretorischen Funktion
der Keimdriisen," Zent. f. Phys., vol. xxiv., 1910 ; " Umstimmung des Geschlechts-
charakters bei Saugethieren dursch Austausch der Pubertatsdriisen," Zent. f.
Phys., vol. xxv., 1911 ; " Willkiirliche Umwandlung von Saugethier-Mannchen,
etc.," Pfliigeijs Arch., cxliv., 1912; "Feminierung von Mannchen und Masku-
lierung von Weibchen," Zent. f. Phys., vol. xxvii., 1913; "Pubertatsdriisen
und Zwitterbildung," Arch. f. Entwick.-Meck., vol. xlii., 1916. Steinach and
Holzknecht, " Erhohte Wirkungen der inneren Sekretion bei Hypertrophie der
Pubertatsdriisen," Arch. f. Entwick.-Mech., vol. xlii., 1916. Steinach and
Kammerer, "Kliniak und Mannbarkeit," Arch. f. Entwick.-Mech., vol. xlvii.,
1921.

4 Lipschutz, " Umwandlung der Clitoris, etc.," Arch. f. Entwick.-Mech.,
vol. xliv., 1918. "On the Internal Secretion of the Sexual Glands," Jour, of
Physiol., vol. li., 1917. Die Pubertatsdruse und ihre Wirkungen, Bern, 1919.
This book contains further information and many references.

332 THE PHYSIOLOGY OF REPRODUCTION

•

testis, and found it to contain normal corpora cavernosa penis as well
as the two quill-shaped horny spikes which are found normally
in the intromittent sac of the male (see p. 258). Sand,1 too, has
described hypertrophy of the clitoris in the masculinised rat. The
latter author has carried out a series of experiments upon the
ligaturing and section of the vas deferens and upon artificially
produced cryptorchism (or the condition in which the testis is
retained in the body cavity, brought about by Sand by occluding the
inguinal canal). These experiments confirm the importance of the
interstitial or puberty gland. Experiments upon the transplantation
of the gonads and upon sex reversal have also been carried out by
Moore,2 and these, together with other experiments by Sand on the
same subject, are described below in the chapter on sex determination.

It has often been stated that an imperfectly descended testicle
in man, notwithstanding the fact that it may be without any
spermatogenic function, is nevertheless of the greatest benefit to
its possessor in virtue of its influence over the metabolism. "The
secondary sexual characters are a far more exact measure of the
value of the testicular tissues than are the presence of spermatozoa
in the external secretion. It may almost be said that a man's male
plumage is in direct proportion to the weight or amount of testicular
tissue present."3 Since the retained or cryptorchid testicle comes
to consist mainly or entirely of interstitial tissue we have here
further evidence that this gland is the organ of the internal testicular
secretion^.4 Lipschutz 5 has shown that in the guinea-pig after partial
castration a portion of testicular tissue one-sixteenth the normal
size is sufficient to admit of the development of the secondary sexual
characters, and he ascribes this result to the functional activity of
the interstitial tissue.

Shattock and Seligmann 6 have described the results of occluding

1 Sand, " Experiments on the Internal Secretion of the Sexual Glands,
especially on Experimental Hermaphroditism," Jour, of PhysioL, vol. liii., 1919 ;
Experimentelle Studien over Kfyiskarakterer hos Pattedyr, Copenhagen, 1918 ;
"Etudes Experimen tales, etc.," I., II., and III., Jour, de Phys. et Path. Gen.,
1921 and 1922.

2 Moore (A.), " On the Physiological Properties of the Gonads, etc.," Jour, of
Exp. Zoo?., vols. xxviii. and xxxiii., 1919 and 1921.

3 Corner, Diseases of the Male Generative Organs, Oxford, 1907. See also
McAdam Eccles, The Imperfectly Descended Testis, London, 1903.

4 For further information and references see Biedl, The Internal Secretory
Organs, English Translation, London, 1917.

5 Lipschutz, " Sur les Consequences de la Castration partielle," C. R. de la
Soc. de Biol., vol. Ixxxiii., 1920.

6 Shattock and Seligmann, "Observations upon the Acquirement of
Secondary Sexual Characters, indicating the Formation of an Internal Secretion
by the Testicle," Proc. Roy. Soc., vol. Ixxiii., 1904. The same investigators
also attempted to obtain further evidence by grafting together two cocks, one
castrated and the other normal, but these experiments were unfortunately a
failure, one of the birds always dying after a short time. (Trans. Path. Soc.,
vol. xlvi., 1905.)

THE TESTICLE AND THE OVARY 333

the vasa deferentia in Herdwick rams and in fowls, and these point
in the same direction. The animals operated upon acquired full
secondary characters. The authors suppose, therefore, that the
development of these characters is. not brought about by metabolic
changes induced by a nervous reflex arising from the function of
sperm ejaculation.

Foges l has described the effect of removing the testes of fowls
and transplanting them to abnormal positions in the body cavity.
In the successful experiments it was found that the presence of
functional transplanted testes exercised the same influence over the
development of the secondary sexual characters as testes growing in
the normal position, and that the appearance of "capon" characters
was averted, the comb, wattle, spurs, etc., being developed as in
uncastrated cocks. Foges concludes that the testes are organs of
internal secretion, and control the development of the male
characters.

Shattock and Seligmann have also described the effects of
testicular transplantation and incomplete caponisation in fowls.
In certain cases the testes are stated to have broken up during the
operation, so that minute fragments were retained, sometimes being
left in the normal position, and sometimes becoming dislocated and
attached to the adjacent viscera or to the abdominal wall. Although
these pieces of testicular substance continued to produce spermatozoa,
they were virtually ductless glands.2 In such cases the secondary
sexual characters of the cock developed to a varying extent which
seemed to depend upon the amount of testicular substance left
behind. "One must regard the external character of maleness as
a quantity which varies proportionately with the amount of gland
tissue present " (but see p. 338).

According to Loewy,3 the injection of testicular substance into
young capons causes the development of normal male skeletal
characters, as well as a better growth of the comb, etc. Further-
more, Walker 4 states that, in two experiments in which he injected
saline extract of cocks' testicles into two hens daily for several
months, the combs and wattles grew in size and became more
brightly coloured, reaching a maximum in five months. When the

1 Foges, "Zur Lehre der secundaren Geschlechtscharaktere," Pfliiger's Arch.,
vol. xciii., 1903. For an account of an earlier and less complete investigation
see Hanau, " Versuche liber den Einfluss der Geschlechtsdriisen, etc.," Pflugeijs
A r<:/t.t vol. Ixv., 1897. See also Sellheim (loc. cit.\ who says that the weight of
the brain is slightly less in the capon (see above, p. 325). And see Cunningham,
loc. cit.

2 Confirmed by Mackenzie and the author (unpublished experiments).

3 Loewy, " Neuere Untersuchungen zur Physiologic der Geschlechtsorgane,"
Ergebnisse der Phys., vol. ii., 1903.

4 Walker (C. E.), "The Influence of the Testis upon the Secondary Sexual
Characters of Fowls," Proc. Roy. Soc. Med.y vol. i., 1908.

334 THE PHYSIOLOGY OF REPRODUCTION

injections were discontinued, the combs and wattles underwent
shrinkage and eventually became reduced almost to their original
condition. Geoffrey Smith,1 however, on repeating the experiments,
obtained negative results, and is of opinion that the effects obtained
by Walker were really those of normal periodic growth.

The effects of castration in the cock are thus summed up by
Morgan 2 who bases his description mainly upon the results obtained
by Goodale3: "The feathers are little changed; some of them, the
hackles especially, become longer. The lowermost tier of wing
coverts are elongated as compared with those of the cock. The
spurs are practically the same in the capon and cock. The capon is
disinclined to give voice, but at times he crows. The moulting is
not affected. The size of the capon is larger. He pays little
attention to the hens. He is not pugnacious, and if attacked will
not often fight. As a rule, he does not pursue the hens, but if a hen
squats down as the capon approaches he will mount and go through
the characteristic mating reaction. The comb is extremely small,
much smaller than that of the female of the same race ; it is infantile
rather than feminine."

Pezard's results 4 are similar. He found castration inhibited the
growth of the erectile organs (comb, wattles, etc.), the capacity to
crow, and the fighting instincts, etc. The spurs and general plumage
were not affected. Castration in pheasants led to practically identical
results. In a general way castration in the male and ovariotomy in
the female produced a neutral type identical in each case. Injection
of interstitial testicular extract prepared by aqueous maceration of
gland of pig caused the comb, etc., to grow completely, but with
the cessation of the injections regression took place. By grafting
testicular tissue on to a castrated hen rapid growth of the comb could
be induced. Injections into castrated males caused similar results,
the lighting instinct being regained.

The question as to the precise elements responsible for the
production of the internal testicular secretion is discussed by Morgan
and by Pezard. The former investigator was the first to show that in
Sebrights and some other varieties of poultry in which the cocks are
often " hen-feathered " castration resulted in the development of male

1 Smith, " Studies on the Experimental Analysis of Sex," Part 5, Quar. Jour.
Micr. Science, vol. Ivi., 1911.

2 Morgan, The Genetic and Operative Evidence relating to Secondary Se.vual
Characters, Carnegie Inst. (Washington) Pub. No. 285, 1919.

3 Goodale, Gonadectomi/, Carnegie Inst. (Washington) Pub. No. 243, 1916.

4 P6zard, "Le Conditionnement Physiologique des Caracteres Sexuels
Secondaires chez les Oiseaux," Thesis, University of Paris, 1918. See also
Comptes Rend, de I'Acad. Sci., 1911, 1917, 1918, 1919, and 1920. Pezard states
(1919) that an exclusively meat diet with cocks leads to genital atrophy and
castration results. For the "Numerical Law of Regression of Certain Secondary
Sex Characters," see Jour. Gen. Phys., vol. iii., 1921.

THE TESTICLE AND THE OVARY 335

plumage and the suppression of the racial " henny " characteristics.1
In such strains Boring 2 found that cells resembling the luteal cells
of the mammalian ovary were present in the testes, but that they
were absent in normal adult cock birds. It was concluded, therefore,
that castrating the Sebright produces its effect by the removal of
these luteal cells which were held to be responsible for the suppres-
sion of cock-feathering. Pease,3 however, has been unable to find
any distinction between normal and henny-feathered cocks in the
matter of testicular luteal cells. In the testes of immature birds or
birds in which spermatogenesis was only beginning, luteal cells could
always be found in both normal and hen-feathered, but in testes
showing active spermatogenesis no luteal cells were seen. Pease,
therefore, is disposed to believe that Morgan and Boring are not
justified in associating luteal cells with hen feathering, and suggests

FIG. 82. — Successive stages in the regression of the comb of the cock after
castration : (a) at the time *bf castration ; (b) five weeks after ; (c) seven
weeks after ; (d) when regression was complete. (From Pezard.)

t

that they may be a source of food for the sperms which are in process
of formation. Boring and Pease both found luteal cells in the ovary of
the female. Boring had previously arrived at the conclusion that there
are no " interstitial cells in the testes of the domesticated chicken in

1 This observation has been confirmed by the present writer working in
conjunction with Professor B. 0. Punnett. It was found further that after
the removal of one testis only in hen-feathered cocks, " cocky " feathering may
develop on the operated side of the bird. This result may have been due
to injury to sympathetic nerve ganglia. Punnett suggests, however, that in
one bird it may have been a case of premature development of such feathering,
which in the non-occurrence of an operation would have grown at the next
moult, since hen -feathered cocks sometimes do subsequently develop an inter-
mediate type of feathering. (See Punnett and Bailey, "Genetic Studies in
Poultry," III., Jour, of Genetics, vol. xi., 1921. Cf. Bond, "On a Case of
Unilateral Development of Secondary Male Characters in a Pheasant, etc.,"
Jour, of Genetics, vol. iii., 1914.)

2 Boring, "The Interstitial Cells and the supposed Internal Secretion of
the Chicken Testis," Biol. Bull., vol. xxiii., 1912 ; "Sex Studies," Jour, of Exp.
Zool., vol. xxv., 1918. See also Boring and Pearl, "Sex Studies," A not. Record,
vol. xiii., 1917 ; and Boring and Morgan, "Luteal Cells and Hen-Feathering^"
Jour, of Gen. Pkys., vol. i., 1918.

3 Pease, "Note on Professor T. H. Morgan's Theory of Hen Feathering,"
Proc. Camb. Phil. Soc., vol. xxi., 1922.

336 THE PHYSIOLOGY OF REPRODUCTION

the sense that this term has been previously used," and that no internal
secretion is produced by interstitial tissue. Pezard1 believes that
the internal secretion of the testes in birds is localised in the
germiuative cells or in the elements of Sertoli.

Des Cilleuls 2 found that in the cock the appearance of interstitial
cells coincided with that of the secondary male characters, and that
they increase synchronously; also that the cock characters were
well marked at a time when the seminiferous tubules were still
embryonic. Thomsen3 states that the secondary sexual characters
are established in the chick befo're hatching. Boring found that
interstitial connective tissue is very abundant in the testes of newly
hatched chicks, but, as mentioned above, there was no evidence of
secretory function. Reeves 4 observed interstitial tissue in cocks of
5|, 9, and 18 months. The whole question as to the seat of production
of the internal testicular secretion in birds still seems to be obscure.

Goodale 5 has described the effects of removal of the testes in the
duck. The Rouen drake throughout most of the year has the nuptial
plumage which is assumed after the autumn moult. It is in striking
contrast to the plumage of the female, the head being green, and the
breast claret colour, and there are four curved tail feathers. The
breeding season ends in July when the drake assumes the
" eclipse " plumage which is very similar to that of the female.
The head becomes brown and the four tail sex feathers become
straight. The eclipse • plumage lasts until the autumn moult in
October. In the mallard it continues somewhat longer. If,
however, castration is performed the eclipse plumage does not,
appear. This case seems somewhat similar to that of the hen-
feathered cocks described above. Shattock and Seligmann state
that when female wild duck assume the male plumage the spurious
males undergo the seasonal eclipse, although this may be incomplete
and aberrant. The same authors observe also that the periods of
activity and non-activity in the testis of the wild duck, as far as
spermatogenesis is concerned, do not correspond with seasonal changes
in the plumage.

Duerden states that the red skin coloration of the cock ostriches

1 P6zard, loc. cit.

2 Des Cilleuls, " Api-opos du Determinisme des Caracteres Sexuel Secondaires
chez les Oiseaux," Compt. Rend, de la Soc. de Biol., vol. Ixxiii., 1912.

3 Thomsen, "Die Differenzierung des Geschlechts und das Verhaltnis der
Geschlechten beim Huhnchen," Arch. f. Entwick.-Mech., vol. xxxi., 1911.

4 Reeves, " On the Presence of Interstitial Cells in the Chicken's Testis,"
Anat. Record, vol. ix., 1915.

6 Goodale, "Some Eesults of Castration in Ducks," Biol. EidL, vol. xx.,
1910 ; Gonadectomy, Carnegie Inst. (Washington) Pub. No. 243, 1916. See also
Sfcattock and Seligmann, " Observations made to ascertain whether any Relation
subsists between the Seasonal Assumption of the Eclipse Plumage in the
Mallard and the Functions of the Testicle," Proc. Zool. Soc., 1914.

THE TESTICLE AND THE OVARY 337

of North and South Africa as well as the rich dark blue of the
southern variety are dependent upon the presence of the testes, but
that the castrated cock attains the normal black plumage which
distinguishes it from the hen.1

Further evidence that the testis produces an internal secretion
is supplied by Nussbaum 2 as a result of his experiments upon frogs.
At the approach of the breeding season there is formed in the male
frog a thickened pad of skin on the first digit of each fore limb
associated with an increased muscular development in the fore arm.
This modification is preparatory to the act of copulation, when the
male frog uses its arms in embracing the female, and so assists in
pressing out the eggs from the oviduct (see p. 20). If the male frog
be castrated, the pad is not formed and the muscles fail to develop.
Nussbaum found that, if pieces of testis from another frog were
grafted into the dorsal lymph sac of a frog previously castrated, the
secondary sexual characters of the latter developed just as in a
normal frog. The transplanted testes, however, after exerting their
influence in the way described, underwent a gradual absorption.

Nussbaum stated, further, that when the nerves supplying the
first digit were severed, the pad did not develop, this operation being
performed on a normal frog. Similarly if the nerves supplying the
clasping muscle of the fore arm were severed, the enlargement did
not occur. He concluded, therefore, that the internal secretion
formed in the testis had a specific action upon certain local "groups
of ganglion cells, and that the nerves passing from these to the fore
arm and digit convey a stimulus which induces the growth of the
muscle and that of the thickened pad. In support of the view that
the testis exerts its influence upon the metabolism (at least partially)
through the medium of the nervous system, Nussbaum cites an
observation of Weber, according to whom an hermaphrodite finch,
having an ovary on one side of the body and a testis on the other,
showed the characteristic female coloration on the ovarian side and
the male plumage on the side of the testis.

Nussbaum's conclusion has been controverted by Pfliiger,3 who
points out that in other cases the apparent effect of section of nerves
is due to loss of sensibility in the parts affected, in consequence of
which the tissues are not guarded from injury, and further, that the

1 Duerden, " Crossing the North African and South African .Ostrich," Jour,
of Genetics, vol. viii., 1919. The skin of the hen and young bird of both sexes
is grey. Spayed hens assume the black plumage of the cock (see below, p. 344).
Cf. Fitzsimons, "A Hen Ostrich with the Plumage of a^Cock," Agric. Jour.
University of South Africa, vol. iv., 1912.

2 Nussbaum, " Innere Sekretion und Nerveneinfluss," Merkel and Bonnet,
Ergeb. der Anat. und Entwick., vol. xv., 1905.

3 Pfliiger, " Ob die Entwicklung der sekundaren Geschlechts-charaktere vom
Nervensystem abhangt ? " Pflilger's Arch., vol. cxvi., 1907.

338 THE PHYSIOLOGY OF REPRODUCTION

secondary sexual characters of animals are usually arranged symmetri-
cally. The effect produced by one-sided castration is general rather
than local, and the operation has little or no influence in destroying
the symmetry of the sexual characteristics (c/., however, Fowler's
statement about fallow deer, which appears to be exceptional). It is
probable, therefore, that Pfliiger is correct in supposing that the
internal secretion of the testis acts as a direct stimulus upon the cells
of the frog's arm and so induces the development of the sexual pad
and the hypertrophy of the muscle.1

- Meisenheimer2 has confirmed the results of Nussbaum's experiments
on castration and testicular transplantation in the frog, but Smith
and Schuster,3 who have repeated the experiments, while admitting
that the castration effect occurs, were sceptical about the efficiency of
the grafts, their own transplantation experiments being negative.
The latter authors further criticise Nussbauin and Meisenheimer's
conclusions, stating that "the effect of castration, except actually
during the breeding season, is to make the papillre on the thumb-pads
remain essentially in the condition they were at the time of castration."
Meisenheimer's claim to have induced hypertrophy as a result of
ovarian transplantation they regard as quite unproved.

According to Kammerer4 the pad can develop in the breeding
season in Alytes in individuals previously castrated.

There is some evidence to show that, after one-sided castration,
the remaining testis is capable of undergoing a compensating
hypertrophy,5 and according to Ancel and Bouin 6 and others there
is a compensatory enlargement of the interstitial gland. Lipschiitz 7
has thrown some doubt on this conclusion, pointing out that a very
small fragment of testicular tissue suffices for the development and
maintenance of the sexual characteristics, as shown both by himself

1 See also Nussbaum, "Hoden und Brunstorgane, etc.," Pflitger's Arch.,
vol. cxxvi., 1909. For further references to the literature of testicular trans-
plantation, see Boruttau, " Innere Sekretion," in Nagel's Handbuch der Physiologie
des Menschen, Braunschweig, 1906 ; and Harms, Experimentelle Untersuchungen
liber die innere Sekretion der Keimdrusen, Jena, 1914.

2 Meisenheimer, "Ueber die Wirkung von Hoden- und Ovarial Substanz
auf die Sekundaren Geschlechtsmerkmale des Frosches," Zool. Anz., vol. xxxviii.,
1911.

3 Smith and Schuster, " Studies in the Experimental Analysis of Sex,"
Part 8, Quar. Jour. Micr. Science, vol. Ivii., 1912.

4 Kammerer, "Vererbung Erzwungener Formveranderungen, etc.," Arch,
f. Entwick.-Mechanik, vol. xliv., 1919.

6 Ribbert, "Beitrage zur kompensatorischen Hypertrophie, etc.," Arch. f.
Entwick.-Mechanik, vol. i., 1894.

6 Bouin and Ancel, " Recherches sur le Role de la Glande Interstitielle, etc.,"
C. R. de VAcad. 8ci., vol. cxxxvii., 1903; "La Glande Inst., etc.," C. R. de
I'Acad. 8ci., vol. cxxxviii., 1904 ; "De la Glande, etc.," Jour, de Phys. et Path.,
vol. vi., 1904.

7 Lipschiitz, Ottow, Wagner, and Bormann, "On the Hypertrophy of the
Interstitial Cells in the Testicle of the Guinea-pig, etc.," Proc. Roy. Soc., B.,
vol. xciii., 1922.

THE TESTICLE AND THE OVARY 339

and by Pezard, and stating that the hypertrophy of such tissue
(e.g. after the removal of one whole testis and a great part of the
second one), when such hypertrophy occurs, is due to local conditions
of nutrition (i.e. of blood supply), and is not truly compensatory.
The two views are riot necessarily inconsistent, since with other
organs of internal secretion (e.g. the pancreas) it is known that a
small portion of gland tissue will suffice for the needs of the
organism, and yet such organs will sometimes undergo what appears
to be a compensatory regeneration. Moreover, if a minute portion
of gland tissue is really in every way adequate, it is Difficult to
understand why the glands in question (whether testis, or pancreas,
or any other endocrine organ) should be as large as they normally
are. It is not unreasonable to assume, therefore, that the endocrine
organ of the testis when artificially reduced tends to undergo an
hypertrophy to its normal bulk, but that this hypertrophy is
dependent upon local nutritive conditions or blood supply. It must
be pointed out, however, that some investigators (Kyrle,1 Kohn,
Stieve, etc.) are disposed to deny an endocrine function to the
interstitial tissue, suggesting that it exercises a trophic function
in connection with seminiferous cells, or hold with Pezard that
the testicular hormone is produced by the germinative tissue or
the cells of Sertoli. That a condition in which the male sexual
characters have failed to develop may be associated with the
presence of interstitial cells is not unknown, but Lipschiitz2 has
pointed out that the mere existence of these cells is insufficient,
and that to be effective the interstitial tissue must be in a state
of functional activity, whereas this is not always the case.

It has already been mentioned that, according to Aucel and

V

Bouin and others, there is a foetal interstitial gland in the testis
of the developing horse and also in the chick. It would seem
probable that this gland is responsible for the development of the
pre-natal sexual characters in the manner postulated by Lillie in
his theory of the " free-martin." This theory has recently received
remarkable confirmation from the experiments of Minoura, who
was able to produce artificial " free-martins " in the chick by graft-
ing portions of reproductive gland, obtained from other individuals,
on to the chorio-allantoic membrane during the progress of develop-
ment. This work is described below in the chapter on the Deter-
mination of Sex (p. 695).

1 Kyrle, " Ueber die Regenerationsvorgiinge iin tier- und menschlicher
Hoden," Sitzungsber. Akad. Wiss. Wien, vol. cxx., 1911. See also Kohn, Arch,
f. Entwick.-Mechanik, vol. xlvii., 1920; Stieve, Ergebn. d. Anat. u. Entwick.,
vol. xxiii., 1921 ; and Tiedje, Deuts. med. Woch., No. 13, 1921.

2 Lipschiitz, " Balentissement experimentale de la Masculinisation," C. R. de
la Soc. de Biol., vol. Ixxxvi., 1922.

340 THE PHYSIOLOGY OF REPRODUCTION

THE CORRELATION BETWEEN THE OVARY AND THE
OTHER FEMALE ORGANS AND CHARACTERS

It has long been known that the ovary, like the testis, exerts a
profound influence over the metabolism, and that the extirpation of
this organ, no less than castration in the male, leads to very distinct
results. In the human female double ovariotomy, if carried out
before puberty, besides preventing the onset of puberty and the
occurrence of menstruation, produces noticeable effects on the general
form and appearance, as may be seen in adult women in semi-
barbarous parts of Asia, where the natives perform this operation
upon young girls. Such women are said to be devoid of many of the
characteristics of their sex, and in certain cases to present resemblances
to men.

In some female animals, also, the removal or incomplete develop-
ment of the ovaries has been said to lead to the appearance of male
characters. For example, Eorig l records three cases in which female
deer possessed horns, and were found upon examination to show
abnormalities in the ovaries. Darwin 2 also states that female deer
have been known to acquire horns in old age.3

Better instances of this kind of phenomenon have been recorded
from among poultry, game birds, and ducks, which, on growing senile,
have been observed to acquire some of the secondary male characters.
Darwin4 refers to the case of a duck which, when ten years old,
assumed the plumage of the drake. He also mentions an instance
of a hen which in old age acquired the secondary sexual characters of
the cock. Hunter5 described a case of a hen pheasant which had
male plumage correlated with an abnormal ovary, and many other
such instances .have been recorded. Gurney6 states that the
assumption of male plumage is frequently (but not invariably)
associated with barrenness in female gallinaceous birds but not as a
rule in passerine birds. The phenomenon has been observed in black
grouse, capercaillie, wild duck, widgeon, merganser, and various other
species belonging to different orders. On the other hand, Gurney

1 Eorig, "Ueber Geweihentwickelung, etc.," Arch. f. Entwick.-Mechanik,
vol. x., 1900. For sheep, see final footnote, p. 392.

2 Darwin, Variation in Animals and Plants, Popular Edition, London, 1905.

3 Smith (F.) ( Veterinary Physiology, 3rd Edition, London, 1907) states that
female cats, whose ovaries have been removed while young, acquire a head of
the male type (with well developed tissues in the jowl, the exact converse
occurring in castrated males). Herbst, who also discusses this question
(Formative Reize in der Tierischen Ontogenese, Leipzig 1901), expresses the belief
that the gonads in either sex exercise a definite inhibitory influence, preventing
the appearance of the secondary sexual characters of the opposite sex.

4 Darwin, loc. cit.

5 Hunter (J.), "Account of an Extraordinary Pheasant," Phil. Trans., vol.
Ixx., 1780.

6 Gurney, "On the Occasional Assumption of Male Plumage by Female
Birds," Ibis, vol. vi., 5th series, 1888.

THE TESTICLE AND THE OVARY 341

records instances of a hen chaffinch with male plumage and an unlaid
egg, a hen redstart with male plumage and a number of developing
eggs, as well as similar cases of hen pheasants. The male plumage
may be only temporarily assumed. Further examples of the
assumption of male plumage by hen birds are recorded by Shattock
and Seligmann,1 who describe the phenomenon under the name of
allopterotism. Some of these cases are regarded as of the nature
of partial hermaphroditism. It would appear possible that the
secondary male characters are normally latent in the female, and that
the ovaries exert an inhibitory influence over their development. On
the other hand, there is no clear evidence that castration in the male
animal leads to the assumption of female characters, excepting in a
negative sense (i.e. excepting in so far as it inhibits the development
of male characters).

The operation of complete ovariotomy is difficult in birds owing
to the diffuse condition of the ovary and the close proximity of the
vena cava, and in de-sexing pullets (or converting them into
" poullardes ") the usual practice is to remove a portion of the oviduct
or destroy in some other way its functional relation with the ovary.2
This operation is believed to favour growth and fattening, but the
result may be due simply to the fact that the albumen and the other
products of oviducal secretion are no longer produced.

According to Brandt,3 the absence of a functional oviduct may be
correlated with male characters and a normal ovary, this being stated
to be the case in a specimen of Ruticilla phwnicurus, but such a fact
seems on the face of it unlikely excepting on the assumption that a
partial hermaphroditism existed.

Goodale 4 was the first completely to remove the ovary from a bird,
and by employing brown Leghorn fowls in which sexual differentiation
is very marked he obtained very clear results. It was only in young
birds that the ovary was sufficiently compact to make the operation
practicable. In the successful experiments the hen assumed the full
plumage of the Leghorn cock, with red back, black breast, and long
pointed hackle and saddle feathers. Spurs also developed. The
comb and wattles developed irregularly. The birds did not crow.

1 Shattock a.nd Seligmann, "An Example of True Hermaphroditism in the
Common Fowl, with Remarks on the Phenomena of Allopterotism," Trans.
Path. Soc., vol. Ivii., 1906. "An Example of Incomplete Glandular Hermaphro-
ditism in the Domestic Fowl," Proc. Roy. Soc. Med., Path. Section, vol. i.,
(November) 1907.

2 Wright, The New Book of Poultry, London, 1902. Lay cock, Nervous
Diseases of Women, London, 1840.

3 Brandt, " Anatomisches und Allgemeines viber die sogenannte Hahnen-
fedrigkeit und iiber anderweitige Geschlechtsanomalien bei Vogeln," Zeitsch.
f. wiss. Zool., vol. xlviii., 1899. This paper also cites numerous cases of hen
birds assuming male plumage, and many references are given.

4 Goodale, Gonadectomy, etc., Carnegie Inst. (Washington) Pub., 1916.

342 THE PHYSIOLOGY OF REPRODUCTION

FIG. 83. — Ovariotomised brown Leghorn hen. (From Goodale.) The bird
shows male feathering and spurs, but the comb and other erectile structures
are not hypertrophied.

FIG. 84. — Ovariotomised pullet with plumage and spurs of male,
i.e. of neutral type according to Pezard. (From Pezard.)

THE TESTICLE AND THE OVARY 343

Pe"zard 1 obtained results on the whole similar, but concluded that
ovariotomy had no influence on the development of the comb.
Moreover, the sickle and other characteristically male feathers did
not appear. The spayed hen Pezard regards as being a neutral type
like the castrated cock (see above, p. 334). By transplanting
ovarian tissue on to a castrated male the growth of the spurs, etc.,

FIG. 85. — Successive stages in the growth of the spurs of
a hen after ovariotomy : (left) six months after ;
(right) one year after ; (bottom) two years after ;
(top) six years after. (From Pezard.)

could be inhibited and the bird become feminised. Goodale also has
feminised a male bird by ovarian transplantation following on
castration.

Gocdale removed the ovaries from ducks and found that the
spayed female may or may not completely assume the perfect male
plumage. One bird after complete ovariotomy did not even assume
the eclipse plumage but retained the nuptial plumage of the v drake.

1 Pezard, loc. cit. (see above, p. 334).

344 THE PHYSIOLOGY OF REPRODUCTION

Another spayed duck first assumed the nuptial plumage and then the
eclipse plumage of the breed in question, and this in turn (in autumn)
was succeeded by the nuptial plumage again. Morgan l suggests
that in the latter case a slight amount of ovarian tissue might
have been retained.

Duerden2 states that ovariotomy in the ostrich is followed by
retention of the ordinary body colour, but that the normally grey
feathers assume the blackness of the cock. This fact is taken
advantage of by some African farmers, seeing that the plumage of the
male is far more valuable economicallv than that of the hen. Thus

FIG. 86. — Normal Rouen drake. (From Goodale.)

the effects of castration in both male and female are to produce a
similar type (see above, p. 337).

The effect of ovariotomy upon the cow has been studied by
Tandler and Keller 3 who state that it produces a type similar to the
castrated male (that is to say, it causes a convergence of type in the
manner described by P6zard for fowls). The height of the spayed
animal is said to be less than that of the cow. The head is similar
to the steer's head. Pearl and Surface 4 have recorded the assumption

1 Morgan, loc. cit.

2 Duerden, loc. cit. (see above, p. 337).

3 Tandler and Keller, " Die Korperform der Weiblichen Friihkastraten des
Rlndes," Arch. f. Entwick.-Mech., vol. xxxi., 1910. For effect on cats, see above,
footnote, p. 340. And see footnote, p. 358. For sheep, see final footnote, p. 392,

4 Pearl and Surface, Sex Studies, VII., Orono, Maine, 1915,

THE TESTICLE AND THE OVARY

345

•

FIG. 87. — Normal Rouen duck. (From Goodale.) (Cf: Figs. 86, 88, and 89.)

FIG. 88. — Ovariotomised Rouen duck — Type I.
(From Goodale.)

(Cf. Figs. 86, 87, and 89.) The bird was operated
upon when six weeks old.

346 THE PHYSIOLOGY OF REPRODUCTION

of male secondary characters by a cow previously normal after cystic
degeneration of the ovaries. Since in this case the interstitial
secreting mechanism of the ovaries was normal, it is suggested that
the full development of secondary female characters is correlated with
the corpus luteum.

Steinach has carried out a number of experiments on rats and
guinea-pigs, producing the converse effect to that described above.1
After transplanting the ovary into previously castrated males when

FIG. 89. — Ovariotomised Rouen duck — Type II.
(From Goodale.)

(Cf. Figs. 86, 87, and 88.) The bird was operated upon
when about a year old.

they were young, very definitely female characters have developed.
Most noteworthy was the growth of the mammary glands and teats,
a feminised male guinea-pig yielding milk and suckling young ones.
Moreover, the hair is said to have resembled that of the normal
female, being finer and softer than in the normal male, and the size
of the body was reduced. Lastly, the feminised animal reacted
sexually like a female as shown especially by the " tail erect " reflex
(normally concerned in coition) and the " kick guarding " reflex (used
to keep off the male before the onset of oastrus). The follicles in the
transplanted ovaries atrophied, but the interstitial cells (or " theca
lutein " cells) remained, and these Steinach regards as representing

1 Page 331.

THE TESTICLE AND THE OVARY 347

the " puberty gland " in the female.1 When the ovaries in women
are subjected to Rontgen ray treatment the climacteric does not
supervene, and this is regarded as being due to the continued
function of the puberty gland.2 Athias and Sand3 have also
studied the development of the mammary glands and the secretion
of milk in castrated males with ovarian grafts.4

The most obvious result of ovariotomy in women before puberty is
that the uterus and oviducts remain infantile, and the breasts fail
to develop.

Ovariotomy performed subsequently to puberty produces less
marked results than when carried out in early life. The most
noticeable effect is the cessation of menstruation, and this is
sometimes accompanied by an atrophy of the breasts and a tendency
towards obesity. Speaking generally, ovariotomy produces an
artificial climacteric.

Most authorities are agreed that the uterus undergoes atrophy
after the removal of the ovaries in adult life, and that castration in
children and young animals arrests the development of the uterus.5
These results are usually ascribed to the absence of ovarian influence,
though a few authors seem disposed to dissent from this view (see
below, p. 376). Thus, Hofmeir 6 and Beukiser 7 ascribe the
degenerative changes to an insufficiency in the blood supply
consequent upon the operation of removal, while Sokoloff 8 and Buys
and Vandervelte9 have supposed these changes to be due to a
severance of nerves passing to the uterus.

In a series of experiments which were performed 10 upon the effects
of ovariotomy in rabbits, it was found that the extent to which the

I For references, see p. 331.

- Steinach and Holzknecht, for. cit.

3 Sand, loc. cit.

4 Athias, "L'Activite secretaire de la Glande Mammaire hyperplasee chez
le Cobaye Male Chatre consecutivement a la Graffe de 1'Ovaire," G. If. de fa 3oc.
de BioL, vol. Ixxviii., 1915.

'"' Kehrer, Px'itrage znr Klin, vnd E.cper. Geburtskunde, Giessen, 1877. Hegar,
Die Kastration der Frauen, Leipzig, 1878. Sellheim, " Die Physiologic dei'
Weiblichen Genitalien," NagePs Handbuch der Physiologic des Menscfien, vol. ii.,
Braunschweig, 1906. This article contains further references.

II Hofmeir, " Ernahrung und Riickbildungsvorgange bei Abdominal-
tumoren," Zeitsch. /. Geburtsh. n. Gynfil:, vol. v.

7 Benkiser, VerhandL d. Deutsch. GeseU. /'. Gynak.t Fourth Congress, 1891.

8 Sokoloff, " Ueber den Einfluss der Ovarienextirpation auf Structur-
verunderungen des Uterus," Arch. f. Gym'ik., vol. li., 1896.

0 Buys and Vandervelte, "Recherches Experimentales sur les Lesions
consecutives a I'Ovariotomie Double," Arch. Ital. de Biol., vol. xxi., 1894.

1M Carmichael and Marshall, "The Correlation of the Ovarian and Uterine
Functions," Pro<\ Hoy. Soc., B., vol. Ixxix., 1907. Bucura (" Beitrage zur
inneren Funktion des weiblichen Genitals," Zeitschr. f. Heilkunde, vol. xxviii.,
1907 ; and " Zur Theorie der inneren Sekretion des Eierstockes," Zent.f. Cri/nak.,
vol. xxxvii., 1914) obtained similar results with rabbits, and Tandler and Keller
(loc. cit.) with cows. See also Shattock (Proc. Roy. Soc. 3fed., Path. Sect., 1910)

348 THE PHYSIOLOGY OF REPRODUCTION

degenerative process was carried was roughly proportional to the
time which had elapsed between the operation and the killing of
the animal. After an interval of six and a half months the uterus
was found to Le in a condition of pronounced fibrosis and to contain
no glands. The epithelium was much attenuated, and the muscle
fibres were broken up. A few small capillaries, however, could still
be seen in the stroma. The Fallopian tubes also underwent atrophy.
In other experiments in which the ovaries were removed from very
young immature rabbits, which were killed after they had grown up,
it was found that the uteri, although they had undergone slight
development, were quite infantile, being no larger than those of rats.
The Fallopian tubes were affected similarly. In all these experi-
ments great care was taken to avoid interference with the blood
supply to the uterus, the uterine branches of the pelvic vessels and
the anastomotic branch of the ovarian artery being left uninjured.
Furthermore, in certain other cases in which hysterectomy was
performed instead of ovariotomy, and which, therefore, may be
regarded as controls to the first series of experiments, the extirpation
of the uterus had no arresting influence on the growth and nutrition
of the ovaries (see p. 379).

Other and more conclusive evidence in support of the theory that
the ovary is an organ of internal secretion is supplied by the results
of various attempts to transplant ovaries in Mammals. The cases of
Morris, Glass, Dudley, and Cramer, who transplanted ovaries from
one woman to another, are described below in discussing the causes
of the menstrual function (p. 360).

Knauer1 has described experiments upon rabbits in which he
removed the ovaries from the normal position and grafted them upon
the mesometrium or between the fascia and the muscle of the
abdominal wall. He found that they could be successfully implanted
on both peritoneum and muscle, but that some portion of the grafted
ovary invariably died. The rest, however, remained functionally
active, and continued to produce ova which were capable of being
fertilised. Knauer states that whereas castration in female rabbits
produced a premature menopause, the uterus undergoing atrophy,
this result was prevented by a successfully transplanted ovary.
Knauer also experimented upon dogs and obtained similar results.

Grigorieff,2 Eibbert,3 and Rubinstein4 carried out experiments

1 Knauer, "Die Ovarien-Transplantation," Arch. f. Gynak., vol. lx., 1900.
See also Cent. f. Gyncik., vol. xx., 1896.

2 Grigorieff, "Die Schwangerschaft bei Transplantation der Eierstocke,"
Central, f. Gyniik., vol. xxi., 1897.

3 Kibberit, " Uber Transplantation von Ovarien, Hoden, und Mamma," Arch,
f. Enttrick.-Mechanik, vol. vii., 1898.

4 Rubinstein, "Extirpation beiden Ovarien," St. Petersburg Mediz. Wochenschr.,
1899.

THE TESTICLE AND THE OVARY

349

FIG. 90. — Transverse section through rabbit's uterus
after ovariotomy, showing degenerative changes.
(From Blair Bell, British Medical Journal and
Trans. Royal Society of Medicine.}

FIG. 91. — Transverse section through bitch's uterus
9£ months after ovariotomy. (From Blair Bell,
British Medical Journal and Trans. Royal Society
of Medicine.)

350 THE PHYSIOLOGY OF REPRODUCTION

upon rabbits which confirmed those of Kiiauer, the ovaries being
transplanted in various abnormal positions. Grigorieff also records
two cases in which ovaries were successfully transplanted from one
individual to another (heteroplastic transplantation). Ribbert found,
in his experiments, that during the first month after transplantation
the peripheral part of the grafted ovary remained unaltered, but the
central part became transformed into connective tissue. At a later
period, however, the central portion was again found to contain
follicles. This fact is attributed to the conditions of increased
nutrition which Ribbert supposed to prevail when the ovaries had
been transplanted for a sufficiently long period to admit of their
having acquired better vascular connections.

Halban l found that the uterus and mammary glands of guinea-
pigs from which the ovaries had been removed shortly after birth,
remained undeveloped ; but, if the ovaries were removed from the
normal position and grafted underneath the skin, the other generative
organs developed normally.

Limon,2 working upon rabbits, grafted ovaries beneath the muscle
layers of the abdominal wall and on to the peritoneum of the .same
individuals. The follicles showed a tendency to degenerate, but the
interstitial cells, after a short period of starvation, subset jiiently
recuperated and acquired a condition of perfect vitality. Limon
states that he found no sign of atrophy in the uterus after the
transplantation of the ovaries to an abnormal position.

Carmichael3 has recorded some success from experiments in

1 Halban, " Ueber den Einfluss der Ovarien auf die Entwickelung des
Genitales," Monatschr. f. Gelurtsh.fu. Gynak.,\o\. xii., 1900.

2 Limon, "Observations sur 1'Etat de la Glande Interstitielle dans les Ovaries
Transplantes," Jour, de Phys. et de Path. Gen., vol. xvi., 1904.

3 Carmichael, "The Possibilities of Ovarian Grafting in the Human Subject,
etc.," Jour, of Obstet. and Gyncec., March 1907. Ovarian transplantation
in different species of animals has also been carried out by Herlitzka
("Recherches sur la Transplantation des Ovaries," Arch. Ital. de Biol.,
vol. xxxiv., 1900), Foa (" La Graffe des Ovaries en Relation avec Quelques
Questions de Biologie," Arch. Ital. de Biol., vol. xxxiv., 1900), Schultz ("Trans-
plantation der Ovarien auf Mannliche Tiere," Central, /. All. Path. u. Path.
Anat.y vol. xi., 1900), Guthrie ("Successful Ovarian Transplantation in Fowls,"
Internat. Congress of Phys., Heidelberg, 1907, Abstract in Zent. f. PhysM.,
vol. xxi., 1907 ; "Further Results of Transplantation of Ovaries in' Chickens,"
Jour, of Exp. ZooL, vol. v., 1908). Schultz and other investigators, without
reference to the ovarian secretion theory, grafted the ovaries of guinea-pigs
on to the bodies of males and recorded some success. Herlitzka also grafted
the ovaries of guinea-pigs on to other individuals (heteroplastic trans-
plantation), some females and some males. Only one experiment was at all
successful, the ovary being transplanted on to a female. Foa was successful
with several heteroplastic grafts in rabbits, and even succeeded in inducing
pregnancy in an animal with a transplanted ovary. Guthrie's experiments
were upon fowls. He states that the ova in the heteroplastically transplanted
ovaries were influenced by the " foster-mother " (i.e. the birds into whom they
were grafted), since the offspring produced by fertilising these ova partook of
some of the foster-mother's characters (but see p. 209). For further references

THE TESTICLE AND THE OVARY

which the ovaries of rabbits were transplanted on to abnormal
positions in the same individuals (homoplastic transplantation), but
there is no evidence in those cases that the grafted ovaries had any
influence in preventing the degeneration of the uterus.

The present writer also, working in conjunction with Dr. Jolly,1

FIG. 92. — Section through ovary of rat after transplantation on to peri-
toneum, showing ovum, normal follicles, and follicles which have
undergone cystic degeneration. (From Marshall and Jolly.)

carried out a series of experiments upon rats in order to determine
whether any histological changes occurred in the uterus after trans-
see Marshall and Jolly, "Results of Eemoval and Transplantation of Ovaries,"
Trans. Roy. Soc. Edin., vol. xlv., 1907, and " Heteroplastic Transplantation,
etc.," Qnar. Jour. Exp. Phys., vol. i., 1908 ; Sauve, Les Greffes Ovariennes, Paris,
1909 ; Sand, loc. cit., and Moore, loc. cit. Guthrie and Lee describe partially
successful heteroplastic ovarian transplantation in dogs (Jour. Airier. Med.
Assoc., vol. Ixiv., 1915). See also Minoura, p. 695, below.
1 Marshall and Jolly, loc. cit.

352 THE PHYSIOLOGY OF REPRODUCTION

planting the ovaries to new situations. Other experiments were
undertaken in which the ovaries were simply removed without being
transplanted. The rats were killed at intervals varying from one
to fourteen months after the operation. In the control animals

FIG. 93. — Section through ovary of rat after transplantation on to peri-
toneum, showing corpora lutea and small follicle with ovum. (From
Marshall and Jolly.)

pronounced fibrosis or other atrophic appearances were always found
in the uterus. On the other hand, in those animals in which ovaries
had been successfully transplanted on to abnormal positions (such as
on to the ventral peritoneum or into one of the kidneys) the uterus
was found undegenerated. If, however, the ovarian graft failed to
" take," or was only partially successful, the uterus presented

THE TESTICLE AND THE OVARY

353

undoubted signs of degeneration. In the cases of transplantation
from rat to rat, as in homoplastic transplantation, uterine degenera-
tion was found to be arrested by a successful ovarian graft.

The successfully transplanted ovaries exhibited all the character-
istic histological features of normal ovarian tissue, excepting that the
germinal epithelium was invariably absorbed after the lapse of a

..
: ', .:,

:.^~ ••^S'

'm -^m
' ...-• ..;., . '&

^^^.//•••••Jr

FIG. 94. — Transverse section through normal uterus of rat.
(Cf. Figs. 95 and 96. From Marshall and Jolly.)

short interval. In some cases a certain amount of degenerative
change took place, only certain elements of the tissue being recog-
nisable after the lapse of several months ; thus, the stroina might
present its normal appearance while the follicles had disappeared,
or the greater part of the graft might be composed of luteal tissue
alone. It was also observed that the successfully transplanted
ovaries underwent the same cyclical changes as normal ovaries.
Thus, in animals killed shortly before the commencement of the

354 THE PHYSIOLOGY OF REPRODUCTION

breeding season, large follicles were found in the grafts, while at a
later period corpora lutea were present, showing that ovulation had
occurred in the transplanted ovaries. In one case, a homoplastic
graft was found to be normal after fourteen months, while a normal
heteroplastic graft was composed entirely of healthy ovarian tissue
(with follicles and ova) after six months. In these experiments the
ovaries were grafted into the substance of the kidneys.

Homoplastic transplantation was
found to be more easily accom-
plished than heteroplastic trans-
plantation. This result could hardly
be ascribed to increased difficulties
in the performance of the latter
operation, since the technique was
identical in each case. Further-
more, our successes in heteroplastic
transplantation were usually obtained
in experiments in which two rats
from the same litter were known to
have been employed, so that the
ovaries were grafted into whole
sisters, but "we were not sure of the
relationship in every case.

These experiments clearly indicate
that the nature of the ovarian influ-
ence is chemical rather than nervous,
since the successfully grafted ovaries,
while still maintaining their func-
tions, had lost their normal nervous
connections. It is probable, there-
fore, that the uterus depends for its
proper nutrition upon substances
secreted by the ovaries.
. Further evidence in support of
the view that the ovary produces an
internal secretion is provided by the results of ovarian medication
or the administration of preparations of ovarian substance for
medicinal purposes. It is somewhat difficult, however, to know
precisely what value to assign to this practice about which medical
authorities still appear to differ. Brown-Sequard l seems to have been
the first to employ ovarian extracts medicinally. He supposed them
to produce similar effects to those brought about by testicular extracts,

FIG. 95. — Transverse section
through uterus of rat after
ovariotomy, showing degen-
erative changes.

(Cf. Figs. 94 and 96. From
Marshall and Jolly.)

1 Brown-Sequard, "Des Effets produits chez PHomme par des Injections,
etc," C. It. de la Soc. de Bid., 1889.

THE TESTICLE AND THE OVARY

355

but they did not appear to be so powerful. Since Brown-Sequard's
time ovarian preparations have been used medicinally in a large
number of cases with more or less successful results. The fresh
ovaries are themselves taken, or ovarian tissue is given in the form of

*B?*V Hi '*.*•• -'-'<•

4^^«fe',^

.*•.-•• AVS-Ai - , ' ',••'.: ,'t.f - ' ••••• : •'. •• '

wtgi&l*

A:*/'-*i*?

FIG. 96. — Transverse section through uterus of rat after ovarian
transplantation. The uterus is normal.

(See tezt and cf. Figs. 94 and 95. From Marshall and Jolly.)

fluid or powder (ovarine, oophorine, ovigenine, etc.). The fresh ovaries
or ovarian powder are eaten, but the fluid can be administered either
by the mouth, by the rectum, or by hypodermic injection. These
methods of treatment are said to have met with considerable success
in cases of amenorrhcea, chlorosis, and menopause troubles, both
natural and post-operative. Some physicians, however, report only

356 THE PHYSIOLOGY OF REPRODUCTION

a very moderate or doubtful success, while a few state that the results
are nearly always unsatisfactory.1 The method of administering the
extract by the mouth is open to the criticism that the "active
principle " of the ovarian secretion may be altered in the metabolic
processes of digestion. Moreover, it is by no means certain that the
" active principle " may not be destroyed in the manufacture of the
preparations. Again, it is not unlikely that the effects of ovarian
medication may depend, not only upon the method of preparing the
extracts, but also upon the condition of the ovaries from which the
extracts are made, and it would seem unreasonable to expect to obtain
uniform results from the indiscriminate usage of ovaries in different
stages of cyclical activity (e.g. ovaries with prominent follicle! like
those from animals " on heat," or ovaries with corpora lutea like those
of pregnant animals, or ovaries in a state of relative quiescence like
those of anoestrous animals). Nevertheless ovarian medication
frequently in conjunction with the usage of other gland extracts
(mammary gland or thyroid) continues to be practised, and in many
instances valuable results are said to be obtained.

The effects are discussed at some length in a memoir by Bestion
de Camboulas,2 who describes a large number of experiments upon
dogs, rabbits, and guinea-pigs, as well as a series of clinical observa-
tions. Experiments were performed on male animals as well as on
female ones. The lethal injection of ovarian extract was found to be
about twice as much in non-pregnant females as in males or pregnant
females. "With non-toxic doses the females gained weight, but the
males lost weight. The lesions discovered after lethal doses were
congestion of the viscera, and minute haemorrhages in the dorsal and
lumbar regions of the spinal cord. Bestion also administered ovarian
extract to his patients, and states that he obtained distinctly beneficial
results. Menopause troubles are described as either disappearing
altogether or becoming much ameliorated, while rapid improvement
was observed in cases of chlorosis and amenorrhrea. Bestion says
that ovarian extract should never be administered to pregnant
women, since "it causes such grave results when given to pregnant
animals.

Jentzner and Beuttner 3 found that the subcutaneous injection of
ovarian extract in castrated animals did not supply the place of living
ovarian substance, and Mr. Carmichael and the present writer4
experienced a similar result after making a series of intra-peritoneal

1 For references to the literature of ovarian medication, see Andrews,
" Internal Secretion of the Ovary," Jour, of Obstet. and Cfyn., vol. v., 1904.

2 Bestion de Camboulas, Le Hue Ovarien, Paris, 1898.

3 Jentzner and Beuttner, " Experimentelle Untersuchungen zur Frage der
Castrationsatrophie," Zeitsch. f. (jleburtsh. u. Gynttk.t vol. xlii., 1900.

4 Carmichael and Marshall, loc. <-it.

THE TESTICLE AND THE OVARY

357

injections of commercial extract, the uterine atrophy which followed
ovariotomy being in no degree diminished.

'-;:^:^^ '

FIG. 96A. — Section through rat's kidney, into the tissue of which an ovary
had been transplanted. (From Marshall and Jolly, (}uar. Jour, of
Experimental Physiology.')

at; Artery ; c.l.t corpus luteum ; g.r., Graafian follicle ; gl., glomerulus of
kidney ; ov.st., ovarian stroma ; r.t., renal tubule ; z.fl.t., zone of
granulation tissue between ovarian tissue and tissue of kidney.

It has been shown that the ovary possesses considerable capacity
for regenerating tissue after partial removal, and also that if one
ovary is extirpated the remaining one may undergo an apparent
increase in size, which is probably of the nature of a compensatory

358 THE PHYSIOLOGY OF REPRODUCTION

hypertrophy. These facts may perhaps be regarded as supplying
some further evidence that the ovary is an organ of internal secretion l
(cf. the testis, p. 338). Lipschutz,2 however, while confirming the
above recorded observations, states that the augmentation in the
ovarian volume is due to the growth and increase of the follicles.

According to Loisel,3 the ovary fulfils a purifying function in the
organism, and absorbs injurious products. This theory seems to have
little experimental basis.4

THE FACTORS WHICH DETERMINE THE OCCURRENCE
OF HEAT AND MENSTRUATION

Ptiiiger 5 advanced the theory that menstruation is brought about
by a nervous reflex, owing its origin to the pressure of the growing
Graafian follicles upon the nerve endings in the ovary. This view
received some support from Strassmann,6 who claimed to have induced
"heat" in animals by injecting gelatine into their ovaries, and so
producing intra-ovarian pressure. Elizabeth Winterhalter's 7 alleged
discovery of a sympathetic ganglion in the ovary also tended to
support this theory; but von Herff8 discredited her description,
which, so far, has received no confirmation.

Goltz9 showed that heat in animals is not brought about by a
cerebral or spinal reflex. In one experiment the spinal cord of a bitch
was transected in the lumbar region ; normal procestrum, followed
by oestrus and conception, occurred as usual, but copulation was
unaccompanied by sensation, though the animal showed a marked
inclination towards the dog. In another experiment the lumbar
part of the spinal cord was completely removed without interfering
with the cyclical recurrence of prooestrum and oestrus. Moreover,

1 Carmichael and Marshall, "On the Occurrence of Compensatory Hyper-
trophy in the Ovary," Jour, of Physiol., vol. xxxvi., 1908.

2 Lipschutz, "Wagner, and Tamen, "Sur PHypertrophie des Fragments
Ovariens dans la Castration Partielle," C. It. de la 8oc. de Biol., vol. Ixxxvi., 1922.

3 Loisel, " Les Poisons des Glandes genitales," C. R. de la Soc. de Biol.,
vol. lv., 1903 ; vol. Ivi., 1904 ; and vol. Ivii., 1904.

4 Ovariotomy has an effect on the skeleton comparable to that of castration.
See Shattock and Seligman, " The Influence of Oophorectomy upon the Growth
of the Pelvis/' Proc. Roy. 8oc. Med., Path. Sec., 1910.

5 Pfliiger, Uber die Bedewtung und Ursache der Menstruation, Berlin, 1865.

6 Strassmann, Lehrbuch der gerichtlichen Jfedizin,l895.

7 Winterhalter, " Ein Sympathisches Ganglion im Menschlichen Ovarium,"
Arch. f. Gyndk., vol. li., 1896.

8 Von Herff, "Giebt es ein Sympathisches Ganglion im Menschlichen
Ovarium," Arch. f. Gynak., vol. li., 1896. For information upon the innervation
of the ovary, see von Herff, " Uber den feineren Verlauf der Nerven im
Eierstock," Zeitsch.f. Geb. u. Gynak., vol. xxiv., 1893.

9 Goltz, " Ueber den Einfluss des Nervensystems auf die Vorgange wahrend
der Schwangerschaft und des Gebarakts," Pfluger's Arch., vol. ix., 1874. Goltz
and Ewald, "Der Hund mit verkurztem Riickenmark," Ptfiiger's Arch., vol. Ixiii.,
1896.

THE TESTICLE AND THE OVARY 359

Sherrington,1 after transecting the spinal cord of a bitch in the
cervical region, and headwards of the connection between the
sympathetic system and the cord, observed that heat of normal
duration and character continued to recur in the animal so operated
upon. The case, described by Brachet,2 of a woman suffering from
paraplegia in the lower part of the body and legs, but who conceived
and became pregnant, may also be cited.

There are other facts which indicate that menstruation is not
caused by a nervous reflex set up by ovulation or by the pressure of
the growing follicles. Gynecologists have pointed out that in the
human subject ovulation and menstruation are not necessarily
associated, and Heape 3 has shown that the ovaries of menstruating
monkeys do not always contain follicles in a state approaching
ripeness.

But whereas the evidence is clear that heat and menstruation are
not brought about by nervous reflexes arising from the ovary, it is
equally obvious that these processes are dependent upon some ovarian
influence. For, if the ovaries are removed, heat and menstruation no
longer take place.

Some authors, however, have denied this, and cases have been
cited of the occurrence of menstruation after surgical ovariotomy.
For example, three cases have recently been described by Doran,4
in each of which the two ovaries were believed to have been removed,
although menstruation recurred at irregular intervals after the
operation. Further cases have lately been reported by Blair Bell 5
and other writers. It seems probable that these exceptional cases
are to be explained on the supposition that the extirpation of
ovarian substance was not quite complete, and that the tissue
which remained behind underwent hypertrophy subsequently to
the operation. That this is the true interpretation is rendered the
more probable in view of the cases referred to by Gordon,6 Doran,7
Meredith,8 and others, in which pregnancy occurred after the
supposed removal of both ovaries (see also p. 370). Doran9 also

1 Sherrington, The Integrative Action of the Nervom System, London, 1906.

2 Brachet, Recherches, 2nd Edition, Paris, 1837.

3 Heape, " The Menstruation and Ovulation of Macaeus rhesus," Phil. Trans.,
B., vol. clxxxviii., 1897.

4 Doran, " Sub-total Hysterectomy for Fibroids," Lancet, Part II., November
1905.

5 Blair Bell, " Preliminary Note on a New Theory of Female Generative
Activity," Liverpool Medico-Chimrgical Journal, July 1906.

6 Gordon, "Two Pregnancies following the Removal of both Tubes and
Ovaries," Trans. A'iner. Gyntec. Soc., vol. xxi., 1896.

7 Doran, " Pregnancy after the Removal of both Ovaries," Joivr. Obstet. and
OyiKKff., vol. ii., 1902.

8 Meredith, " Pregnancy after Removal of both Ovaries," Brit. Med. Jour.,
Part I., 1904.

9 Doran, " Sub-total Hysterectomy for Fibroids," Lancet, Part II., Nov. 1905.

360 THE PHYSIOLOGY OF REPRODUCTION

records a large series of cases in which menstruation entirely ceased
after ovariotomy.1

Morris 2 gives an account of a woman aged twenty, who suffered
from amenorrhcea, her uterus being infantile. He states that he
transplanted on to her fundus uteri an ovary which he obtained from
another woman, aged thirty. The transplantation is said to have
been successful, inducing menstruation after two months. In another
case Morris3 states that he transplanted an ovary into a woman
whose own ovaries had been previously removed, and that the graft
was so far successful that conception, followed by a normal pregnancy,
occurred as a result. It has been suggested, however, that in this
case a portion of the woman's original ovary may have been left
behind, and that this accounted for the pregnancy (cf. p. 359). Glass 4
describes a case of a patient who was suffering from menopause
troubles due to the extirpation of the ovaries. After the transplanta-
tion of an ovary from another woman had been effected, the patient
was gradually restored to health and menstruation was renewed.
Dudley 5 mentions a case in which a double pyosalpinx was removed,
and the right ovary implanted on the fundus uteri. The patient
menstruated regularly afterwards. Again, in a case recorded by
Cramer of Bonn,6 the ovary of a woman suffering from osteomalacia
was extirpated and transplanted into a second woman whose genital
organs were much atrophied. As a result of the graft the genital
organs of the woman in whom the ovary was transplanted became
normal, menstruation started once more, and the breasts secreted
colostrum. In none of these cases, however, is there any record of
post-mortem evidence showing that the transplanted ovaries had
become successfully attached.

Halban 7 states that he found in monkeys that, whereas menstrua-
tion ceased after double ovariotomy, it recurred again after ovarian
transplantation, even though the ovary was grafted in a position
different from the normal one.

1 The continuance of menstruation after the removal of two ovaries may be
due to the presence of accessory ovaries which are occasionally known to exist.
Oliver says that ovariotomy, even when the ovaries are removed with a portion
of the broad ligament, does not necessarily stop menstruation ("On the
Question of an Internal Secretion from the Human Ovary," Jour, of Physiol.,
vol. xliv.,-1912).

2 Morris, "The Ovarian Graft," New York Med. Jour., 1895.

3 Morris, "A Case of Heteroplastic Ovarian Grafting followed by Pregnancy,
etc.," New York Med. Jour., vol. Ixix., 1906.

4 Glass, " An Experiment in Transplantation of the Entire Human Ovary,"
Medical News, 1899.

5 Dudley, "Uber Intra-uterine Implantation des Ovariums," Inttrnat. Gyn.
Congress, Amsterdam, 1899.

6 Cramer (H.), "Transplantation menschlicher Ovarien," Milnchen. med.
Wochenschr., 1906.

7 Halban, "Uber den Einfluss der Ovarien auf die Entwickelnng des
Genitales," Sitz.-Ber. Akad. Wissenschaft, Wien, vol. ex., 1901.

THE TESTICLE AND THE OVARY 361

Those cases already referred to, in which atrophy of the uterus
took place after the removal of the ovaries, also indicate the
dependence of the menstrual and prooastrous functions upon the
presence of ovarian tissue, since normal heat could not occur if
the uterus were in a condition of fibrotic degeneration, while certain
of Knauer's experiments1 afford evidence that heat can be experi-
enced by animals in which the ovaries are transplanted to abnormal
positions.

Veterinarians are generally agreed that heat does not occur in
dogs whose ovaries have been extirpated. Moreover, ovariotomy is
sometimes practised on mares in order to prevent osstrus, and so
suppress the vicious symptoms which are liable to render the animals
periodically unworkable.2

The spaying of sows is a well-known commercial practice, and if
properly carried out prevents the recurrence of "heat." The ordinary
method is to make an incision in the side and withdraw the uterus
along with the ovaries, but sometimes one or both ovaries are left
behind, and the sows come " in use." This has led to the discrediting
of the practice, the importance of removing the minute ovaries
(the pigs being only about seven weeks old) not being properly
appreciated.3

Dr. Jolly and the author4 have shown, further, that normal
proosstrum, followed by oestrus, can occur in dogs which onjy possess
transplanted ovaries, thus confirming the observations of Knauer and
Halban. In the experiments in question the animals' own ovaries
were removed, and a few weeks later the ovaries obtained from
other dogs were grafted in abnormal positions (e.g. between the
abdominal muscular layers or on the ventral border of the peritoneal
cavity). The grafts seem to have become attached, and to have
survived for a sufficiently long period to exercise an influence over
the generative system ; but they eventually underwent consider-
able fibrous degeneration, as the post-mortem evidence afterwards
showed.

As a result of these experiments it may probably be concluded
that the enhanced activity which the ovaries exhibit during the
final stages of follicular development is accompanied by metabolic
changes which result in an increase in the production of the ovarian
secretion, and that this phenomenon is the main factor in the periodic

1 Knauer, loc. cit.

2 Hobday, " Ovariotomy of Troublesome Mares," Veterinary Jour., New
Series, vol. xiii., April 1906.

3 Mackenzie and Marshall, "Ovariotomy in Sows, etc.," Jour, of Agric.
Science, vol. v., 1913. See below, p. 389.

4 Marshall and Jolly, "Contributions to the" Physiology of Mammalian
Reproduction : Part II. The Ovary as an Organ of Internal Secretion," Phil.
Trans., B., vol. cxcviii., 1905.

12 A

362 THE PHYSIOLOGY OF REPRODUCTION

recurrence of heat and menstruation.1 It has been observed that
not only are the internal and external generative organs affected at
these periods, but there is also a distinct hypertrophy of the breasts,
and this, as Miss Lane-Claypon and Starling z have pointed out, is
probably clue also to an increase in the ovarian metabolism.3

There is a certain amount of direct evidence that heat and
menstruation are brought about by an internal secretion elaborated
by the ovaries. It has been found that the injection of fresh ovarian
extract obtained from animals which are " on heat " may appear to
produce in ancestrous animals a transient congestion of the external
generative organs resembling that of the normal procestrous condition,
but similar slight indications have been observed at other times
irrespectively of any injections.4 Miss Lane-Claypon and Starling
also have described congestion in the uterus after the injection of
ovarian extract; but, in their experiments, the ovaries employed
were those of pregnant animals. Moreover, Aschner 5 has described
uterine haemorrhage after injection of ovarian extracts.

Further evidence that the procestrous and oestrous conditions are
produced by substances circulating in the blood, but not necessarily
elaborated in the ovaries, is supplied by certain facts recorded by
Halban.6 This author affirms that the milk of suckling sows is
affected during the periods of heat, in consequence of which the
young are liable to develop unhealthy symptoms. In a similar way
the milk of women is said to be affected during menstruation.
Moreover, according to Youatt,7 cows can be brought "on heat"
artificially by feeding them on milk supplied from other cows which
are in that condition.

1 As already pointed out, menstruation and ovulation are not necessarily
associated. It is probable, however, that the ovarian metabolism is increased
at the menstrual periods, although there may not always be any follicles present
in a sufficiently mature condition to admit of ovulation occurring in the
cestrous periods which normally follow them.

- Lane-Claypon and Starling, "An Experimental Inquiry into the Factors
which Determine the Growth and Activity of the Mammary Glands," Proc.
Roy. 8oc., B., vol. Ixxvii., 1906.

:! According to Pearl and Surface ("The Nature of the Stimulus which
causes a Shell to be formed on a Bird's" Egg," Science, New Series, vol. xxix.,
1909), the stimulus which excites the activity of the shell-secreting glands in
the fowl's oviduct is mechanical, being brought about by a strictly local reflex.
The shape of the egg is determined by the muscular activity of the cells of
the oviduct (Pearl, " Studies on the Physiology of Eeproduction in the Domestic
Fowl : I. Regulation in the Morphogenetic Activity of the Oviduct," Jour,
of Exp. Zool., vol. vi., 1909).

4 Marshall and Jolly, loc. cit.

5 Aschner, "Ueber brunstartige Erscheinungen (Hyperamia und Hamor-
rhagia am weiblichen Genitale) nach subkutaner Injektion von Ovarial- und
Plazentaextrakt," Arch. f. Gi/nak., vol. xcix., 1913. Cf. Iscovesco, C. R. de Soc. fa
Biol.. vol. Ixxiii., 1912.

c Halban, loc. cit.

7 Youatt, Cattle, London, 1835.

THE TESTICLE AND THE OVARY 363

Heape * has suggested that heat may be due to a " generative
ferment " which he supposes to be periodically present in the blood.
At the same time he is of opinion that a hypothetical substance
called " gonadin," which is secreted by the generative glands, is also
an essential factor. The precise relation in which gonadin and the
generative ferment were supposed to stand to one another is not
very clear.

Assuming that heat and menstruation are brought about, either
directly or indirectly, through a stimulus depending upon the
secretory activity of the ovary, it is still an open question as to
what part of the organ is concerned in the process. Fraenkel 2 has
supposed that the secretion in question is supplied by the corpus
luteum. This conclusion is based upon nine cases in which the
corpus luteum was destroyed by the cautery, and in eight of which
the next menstrual period was missed. In the remaining case it is
supposed that the secretion responsible for producing menstruation
had already been formed in sufficient quantity and passed into the
circulation at the time of the cauterisation. Fraenkel's theory,
however, is disproved by the fact that ovulation in most Mammals
does not occur until oastrus, or, at any rate, until the end of the
prooestrum (see p. 131), and consequently corpora lutea are not
present in the ovaries (for the corpora lutea dating from one oastrus
do not always persist until the next oestrus, which may be many
months afterwards). Heape's observations3 on the absence of
corpora lutea in menstruating monkeys may be again cited in this
connection. Moreover, Kies*4 has reported a case of a woman with
whom menstruation occurred normally after an operation in which
an oozing corpus luteum, which was a source of haemorrhage in the
peritoneal cavity, had been peeled1 out. It should be mentioned that
Fraenkel's views on menstruation are part of a general theory which
is discussed more fully below (p. 368).

Seeing that the corpus luteum is not responsible for inducing
menstruation, it becomes necessary to conclude that either the
follicular epithelial cells or the interstitial cells of the ovarian stroma
(or both of these) are concerned in bringing about the process
(see p. 119).

Some experiments by Mr. Runciman and the author 5 on bitches

1 Heape, "Ovulation and Degeneration of Ova in the Rabbit," Proc. Roy.
>S'oc., B., vol. Ixxvi., 1905.

2 Fraenkel, " Die Function des Corpus Luteum," Arch. f. Gynak., vol. Ixviii.,
1903.

3 Heape, "The Menstruation and Ovulation of Macacus rhesus" Phil. Trans.,
B., clxxxviii., 1897.

4 Ries, "A Contribution to the Function of the Corpus Luteum," Amer.
Jour. Obstet., vol. xlix., 1904.

5 Marshall and Runciman, "On the Ovarian Factor concerned in the
Recurrence of the CEstrous Cycle," Jour, of P/iysioL, vol. xlix., 1914.

364 THE PHYSIOLOGY OF REPRODUCTION

point to the conclusion that the presence of mature follicles is not
essential for the recurrence of heat. All the follicles approaching
ripeness were ruptured artificially by pricking three weeks and two
months before heat periods were due. In both cases heat appeared
at about the normal time. The inference was that the process of
follicular maturation and the phenomena of heat are both effects of
some further factor which must be sought for in the ovaries elsewhere
than in the ripe Graafian follicle. As Robinson points out, interstitial
tissue may be found in the bitch's ovaries, but according to
O'Donoghue1 it is not always present in the ovaries of Mammals.
Robinson 2 expresses the view that the cells of the ruptured follicles
were not necessarily functionally interfered with, notwithstanding
the fact that they later developed into cells resembling those of
corpora lutea. He states further that in ferrets oestrus only occurs
when the ovaries contain follicles of a certain degree of development,
and that such follicles are present as long as oestrus persists. This
particular stage of development he calls the preinseminal stage when
the follicles "appear to take on the function of providing the
secretion which is responsible for the phenomena of prooestrum
and osstrus." 3

It has already been shown that the breeding season, and
consequently the recurrence of the oestrous cycle, are controlled to a
great extent by the general environmental conditions, since these
affect the physical state of the body (Chapters I. and II.). This is
particularly well seen in certain of the domestic animals, in which
" heat " may be caused to recur more frequently by the supply of
special kinds of stimulating foods (p. 635). It would appear,
therefore, that the metabolic activity of the ovaries is increased
by these methods, and that the problematical internal secretion is
elaborated in greater quantity.

Lastly, it must not be forgotten that, whereas it is exceedingly
probable that the prooestrous changes of the uterus are brought
about by a specific excitant or hormone 4 arising in the ovaries, little
or nothing is known concerning the chain of causation leading to
that disturbed state of the nervous metabolism, the existence of

1 O'Donoghue, "On the Corpora Lutea and the Interstitial Tissue in the
Ovary and in Marsupialia," Quar. Jour. Micr. Science, vol. Ixvi., 1916.

2 Robinson, "The Formation, etc., of Ovarian Follicles in Ferrets," Trans.
Roy. Soc. Edin., vol. Hi., 1918.

3 For further information see Bucura, " Zur Theorie der inneren Sekretion
des Eierstocks," Zent.fur Gyn., 1913.

4 Starling has proposed the term hormone (from the Greek, 6#taw, I excite
or arouse) for such internal secretions or excitants of a chemical nature. Thus,
secretin, or the internal secretion of the duodenum, which excites pancreatic
secretion, is a hormone. See Starling, "The Chemical Correlation of the
Functions of the Body," Croonian Lectures, London, 1905 ; also Lane-Clay pon
and Starling, loc. tit.

THE TESTICLE AND THE OVARY 365

which during oestrus is so plainly manifested in the display
of sexual feeling.

THE FUNCTION OF THE "CORPUS LUTEUM

Various theories have been put forward to explain the formation
and presence of the corpus luteum. According to one view, which was
taught until recently, the development of this structure was merely
a result of the excessive vascularisation which characterises the
entire internal generative tract during the period of pregnancy. Very
little consideration of the actual facts is needed to convince one of
the inadequacy of this explanation. The blood supply to the
generative organs is greatest during the later stages of pregnancy,
when the corpus luteum is becoming diminished in size. Moreover,
the rapid hypertrophy of the luteal cells takes place independently
of pregnancy during the very early stages of development at a
time when there is no appreciable congestion of the genital
organs. According to another theory, the corpus luteum was of
the nature of a stop-gap, whose purpose was to preserve the cortical
circulation of the ovary by preventing an excessive formation of
sear-tissue.1

Prenant 2 seems to have been the first to suggest that the corpus
luteum was a ductless gland. He supposed it to produce an internal
secretion which exercised an influence over the general metabolism
in the manner attributed to the internal ovarian secretion. The
phenomenon of chlorosis was explained as being due to the absence
of this secretion. Prenant supposed also that the corpus luteum had
the further function of preventing ovulation during pregnancy or.
between the oestrous periods.

This theory was supported by Eegaud and Policard,3 who stated
that, by means of special methods of staining, droplets of a secretory
substance could be detected in the cells of the corpus luteum of the
hedgehog.

Beard4 independently suggested that the corpus luteum is a
contrivance to suppress ovulation during pregnancy, while he supposed
it to degenerate before parturition in order to admit of ovulation
occurring immediately afterwards. It must be pointed out, however,
that in many Mammals, if not in the majority, the breeding season

1 Clark, "Ursprung, Wachstum, und Ende des Corpus Luteum," Arch. f.
Anat. n. Phys., Anat. Abth., 1898. Whitridge Williams, Obstetrics, New York,
1903.

2 Prenant, " La Valeur Morphologique du Corps Jaune," Rev. Gen. des
Sciences, 1898.

3 Regaud and Policard, "Fonction Glandulaire de 1'Epitheliuin Ovarique
chez la Chienne," C. JR. de Soc. de Biol., vol. liii., 1901.

4 Beard, The Span of Gestation and the Came of Birth, Jena, 1897.

366 THE PHYSIOLOGY OF REPRODUCTION

does not recur until after an anoestrous period, which is often of
considerable duration, and that it is extremely improbable that
ovulation occurs during this period.

Beard's theory has been adopted by Sandes,1 who investigated the
corpus luteum of the marsupial cat (Dasyurus viverrinus, see p. 142).
This author states that in Dasyurus, as in most other Mammals, the
corpus luteum disappears towards the end of the lactation period,
when the next osstrus is approaching, and the follicles are beginning
to grow in preparation for the ensuing ovulation. He says, further,
that as soon as the corpus luteum is formed, the ova in the
surrounding follicles, which were up to that time in various stages
of active development, begin to undergo atrophy. This atrophy
commences in the follicles in closest proximity to the newly formed
corpus luteum, and is continued in the surrounding follicles in ever-
widening circles. Sandes suggests that this result is brought about
by mechanical pressure, or is due to the internal secretion of the
corpus luteum, if it has one. Without in any way disputing the
accuracy of the facts which Sandes describes, it is difficult to under-
stand what advantage is gained by a mechanism having a not more
important object than that of securing the degeneration of the surplus
ova within the ovary instead of externally to it, and it is not easy to
see how, according to the usually accepted doctrines of utility and
natural selection, an organ having such a purposeless function could
ever have been developed at all.2

Gustav Born was the first to suggest that the function of the
corpus luteum might be to provide an internal secretion which
assisted in the attachment of the embryo to the uterine mucosa.
Unable to undertake the investigation himself, he persuaded Ludwig
Fraenkel 3 to put his theory to an experimental test. For this purpose
a series of experiments upon rabbits was proceeded with, the ovaries
being removed at intervals varying from one to six days after the
occurrence of coition, the period of gestation in this animal being
thirty days. The rabbits were afterwards killed, when it was found
that the extirpation of the ovaries had prevented the fixation of the
embryos, or had caused these to be aborted. In other cases the
corpora lutea are described as having been burnt out by the electric
cautery without destroying the rest of the ovaries, and these experi-
ments led to a similar result. Control experiments were performed

1 Sandes, "The Corpus Luteum of Dasyurus viverrinus" Proc. Linnenn <S'or.,
New South Wales, vol. xxviii., 1903.

2 Pearl and Surface state that extract of corpus luteum of cow injected into
a laying fowl inhibits ovulatipn. ("Studies on the Physiology of Reproduction
in the Domestic Fowl," IX., Jour. Diol. Chem., vol. xix., 1914.)

3 Fraenkel and Cohn, " Experimentelle Untersuchungen iiber den Einfluss
des Corpus Luteum auf die Insertion des Eies," Anat. Am., vol. xx., 1901 ;
Fraenkel, loc. fit.

THE TESTICLE AND THE OVARY 367

by removing one ovary while leaving the other, and by destroying
some of the corpora lutea but not all, and in the majority of these
cases the animals produced young. The experiments resulted, there-
fore, in supporting the view that there is an intimate connection
between the presence of the corpus luteum and the occurrence of
pregnancy, and that this connection is in a certain sense one of cause
and effect.

Apart from the experimental evidence, Fraenkel adduces certain
other facts which tend to support the theory that the corpus luteum
is an organ of internal secretion. He points out that its general
structure is eminently suggestive of its being a ductless gland, since
it is formed mainly of large epitheloid cells surrounded by a network
of capillaries and arranged in regular rows or columns not unlike
those of the cortex of the supra-renal body. Moreover, the increase
in the size of the corpus luteum, until it becomes larger than a
Graafian follicle, seems inexplicable on any other view. This unusual
capacity for growth is clearly out of all proportion to that of the
rest of the ovary, and it is pointed out, further, that when the corpus
luteum is most hypenemic, the other part of the ovary is unusually
anemic, while towards the end of pregnancy, when the increase in
the blood supply to the generative organs is at its height, the corpus
luteum is often reduced to little more than a scar. Fraenkel also
lays some stress on the discovery that the luteal cells are derived
from the follicular epithelium and not from the connective tissue of
the stroma. Furthermore, he observes that whereas many cases have
been recorded in which double ovariotomy was performed during
pregnancy without interfering with the further course of development,
in none of these, so far as he is aware, was the operation conducted
in the early weeks.

Fraenkel observes also that in non-placental Mammals (Marsupials
and Monotremes) the corpus luteum is rudimentary or does not exist
at all. Sandes,1 who has carefully described the formation of the
corpus luteum in the marsupial cat, points out that this is erroneous,
and says that there is a large corpus luteum in the members of both
these groups. • It should be remembered, howrever, that in Marsupials
the embryo is nourished by a " yolk-sac placenta," while in at least
one genus (Pcrameles) a definite allantoic placenta exists. In Mono-
tremes there is a pronounced hypertrophy of the follicular epithelium
following upon ovulation, but the corpus luteum is not normal in this
group, since there appears to be no ingrowth of connective tissue or
blood-vessels from the follicular wall (see p. 143).

A similar objection, that might be raised in opposition to
Fraenkel's hypothesis, is that structures resembling corpora lutea

1 Sandes, lo<: cit.

368 THE PHYSIOLOGY OF REPRODUCTION

have been found in the ovaries of certain of the lower Vertebrates
(see p. 145). This resemblance relates chiefly to the hypertrophy of
the cells of the follicular epithelium after the discharge of the ova.
Such an objection is not to be regarded as a serious one, for there is
nothing improbable in the supposition that rudimentary corpora lutea,
providing probably some sort of secretion, should have been developed
before the acquirement of the function, which, according to Fraenkel's
hypothesis, is possessed by the fully formed structure which char-
acterises the placental Mammalia.

Fraenkel has also pointed out, as an argument in favour of his
theory, that in ectopic or extra-uterine pregnancy the uterus under-
goes the usual changes although there is no ovum in the uterine
cavity. It is clear, therefore, that the changes do not occur simply
as a consequence of the presence of the ovum. It is also pointed
out that in normal pregnancy the uterine changes commence before
the ovum enters the uterus.

Again, the theory that the corpus luteum is responsible for the
attachment and early development of the embryo receives some
support from those cases in which pathological conditions in the
embryo have been found associated with pathological conditions in
the corpus luteum.1 Thus lutein cysts are frequently found in
apparent correlation with chorionepitheliomata.

Fraenkel's general conclusions regarding the functions of the
corpus luteum may be summarised as follows : The corpus luteum
is a ductless gland which is renewed every four weeks during
reproductive life in the human female, and at different intervals in
the various lower Mammals. Strictly speaking, there is only one
corpus luteum which represents the ovarian organ of internal secretion,
and is regenerated periodically in slightly different positions in the
ovaries. Its function is to control the nutrition of the 'uterus from
puberty until the menopause, to prevent it from lapsing into the
infantile condition or undergoing atrophy, and to prepare its mucous
membrane for the maintenance of the ovum. If the ovum be
fertilised, the corpus luteum is responsible for maintaining the raised
nutrition of the uterus during the first part of gestation. If the
ovum be unfertilised it merely produces the hypersemia of menstrua-
tion, and then undergoes degeneration until it is renewed in a fresh
position. Since the corpus luteum is, par excellence, the ovarian gland,
"lutein" or the extract of this organ, and not preparations of the
entire ovary, should be employed for the purposes of ovarian
medication.

Reasons have already been given for concluding that this extended

1 Cf. Malcolm Campbell, "Pathological Condition of the Ovaries as a
Possible Factor in the Etiology of Uterine Fibroids," Scottish Med. and Xurg.
Jour., vol. xvi., 1905.

THE TESTICLE AND THE OVARY 369

theory of the meaning and function of the corpus luteum is untenable
(p. 363). The fact that in a very large number of animals, heat, and
presumably, therefore, ovulation, occur at infrequent intervals does
not support it, while it has been shown that, in some animals at any
rate, ovulation does not take place until oestrus, and consequently
that at the time of the proosstrous hypersemia there are no corpora
lutea present in the ovary. These facts, however, are in no way
opposed to that part of Fraenkel's theory which assigns to the corpus
luteum the function of governing the fixation of the ovum and helping
to maintain its nutrition during the first stages of pregnancy.

Dr. Jolly and the author l have carried out a series of experiments
upon dogs and rats in which the ovaries were extirpated at different
stages during pregnancy, as in FraenkePs experiments upon rabbits.
In the experiments on dogs, ovariotomy was performed at intervals
ranging from three days to four weeks after impregnation. The
pregnancy was discontinued in every case excepting one, in which
a portion of the right ovary which contained the degenerate remains
of two undoubted corpora lutea were found post mortem, three days
after parturition, when the dog was killed. In this experiment
ovariotomy was performed three days after copulation, and parturition
occurred fifty days subsequently. Only a single pup was produced,
and birth was premature. The pup died after being suckled normally
for three days. The ovaries were also removed from a large number
of rats, most of which were in early stages of pregnancy. Pregnancy
was continued in no case in which ovariotomy was performed during
the first six days. In other cases, in which the ovaries were removed
at periods varying from the sixth day until near the end of pregnancy,
the young were produced normally at full time.2 Control experiments
were also carried out in which the abdominal cavity was opened up
during an early stage of pregnancy and the ovaries were cauterised,
or in which one ovary was removed and not the other, and in these
experiments the course of pregnancy was not interfered with.3 We
purposely refrained from attempting to extirpate the corpora lutea
only while leaving the rest of the ovary, as it appeared to us to be
practically impossible to destroy the whole of the luteal tissue without
injuring the entire organ. The ovaries during pregnancy consist
very largely of corpora lutea, and any attempt in a relatively small
animal to discriminate between luteal tissue and stroma, while the
ovary was lying in its normal position in the body cavity, seemed in
our judgment to be impracticable.

It will be seen that our experiments on the results of ovariotomy

1 Marshall and Jolly, loc. cit.

2 In our paper the period of gestation in the i^at was wrongly stated to be
twenty- eight days. It is in reality about twenty-one days.

3 Cf. Carmichael and Marshall, loc. cit.

370 THE PHYSIOLOGY OF REPRODUCTION

during pregnancy fully confirm those of Fraenkel. It must be
pointed out, however, that there is no evidence that the corpus luteurn
governs the fixation of the embryo in any other than the indirect
sense implied in the supposition that the secretion elaborated by that
organ acts as a stimulus which excites the uterine mucosa to undergo
the necessary hypertrophy. In this general sense, also, it is probably
true that the luteal secretion (or, at any rate, the secretion of the
ovary) assists in nourishing the embryo during the first stages of
pregnancy, since there is every reason for concluding that it helps to
maintain the raised nutrition of the uterus. It has been shown that
the presence of the ovaries is not essential for the continuance of
pregnancy in the later stages, when the corpora lutea are in process
of degeneration. It would seem not unlikely, therefore, that the
atrophic changes (fibrosis) which take place in the decidua serotina,
or maternal , placenta, in the later part of the gestation period are
directly correlated with the degeneration of the corpus luteum.1

Cases have been recorded by Essen-Moller,2 Graefe,3 and Flatau,4
in which pregnancy was not interrupted by double ovariotomy in
women when performed in the early stages of pregnancy. These
cases .are undoubtedly very exceptional, and it seems legitimate to
conclude that a small portion of an ovary, probably containing luteal
tissue, was left behind accidentally at the time of the operation. So
able and experienced an operator as Bland Sutton5 has recently
testified to the extraordinary difficulty experienced in removing the
whole of the ovarian tissue in ovariotomy, and the distinguished
French obstetrician, Lucas-Champonniere,6 has expressed himself in
the same sense, so that there is nothing unreasonable in the assumption
that the operation of removal is sometimes incomplete when performed
on pregnant women.

Daels 7 has recorded a large series of experiments upon guinea-
pigs and rats in which he found that bilateral castration invariably
interrupted the course of pregnancy during rather more than the
first half of its duration. In control experiments portions of

1 It has been suggested that the co.rpus luteum contributes an essential
factor in the nourishment of the embryo through the trophoblast, and that it
consequently ceases to be functional in the later part of pregnancy when the
trophoblast is superseded by the allantoic placenta. See Andrews, loc. cit.

2 Essen-Moller, " Doppelseitige Ovariotomie im Anfange der Schwanger-
schaft," Central. f. Gynak., vol. xxviii., 1904.

3 Graefe, "Zur Ovariotomie in der Schwangerschaft," Zeitsch. f. Geb. >'.
Gynak., vol. Ivi., 1905.

4 Flatau, "Ueber Ovariotomie wahrend der Schwangerschaft," Arch. f.
Gynak , vol. Ixxxii., 1907.

5 Bland Suttori, "A Clinical Lecture on the Value and Fate of Belated
Ovaries," Medical Press, vol. cxxxv., (31st July) 1907.

0 Lucas-Champonniere, " Sur une Observation de Graffe Ovarienne Suivie
de Grossesse," Jour, de Me'd. et de Ctiirurgie Pratiques, vol. Ixxviii., (May) 1907.

7 Daels, " On the Relations between the Ovaries and the Uterus," Surgery,
Gynaecology and Obstetrics, vol. vi., 1908.

THE TESTICLE AND THE OVARY 371

mesentery or other tissue, or only one ovary instead of both, were
extirpated, and in these cases the pregnancy was continued. Further-
more, Kleinhaus and Schenk l found that destruction of the corpora
lutea of rabbits, after the ninth day of gestation, did not necessarily
produce abortion, but that the same operation at an earlier period
invariably brought the gestation to a premature end.

Ancel 2 and Bouin have shown in a succession of papers that the
rabbit's uterus undergoes growth, vascularisation and muscular
hypertrophy after ovulation, although the ova are not fertilised
(e.g. owing to coition having been sterile through the vasa defer-
entia of the male having been cut). There is a great glandular
hypertrophy of the uterine mucous membrane and active secretion
takes place. These changes are succeeded by regression, when the
blood-vessels break down and corpuscles are extravasated in the
stroma and the glands become smaller. The regression sets' in
about the thirteenth day, or after a period nearly equal to half the
duration of pregnancy. The corpus luteum begins to retrogress about
the same time. There is, therefore, a close parallelism between the
growth and regression of the corpus luteum and a series of cyclical
changes which take place in the uterus. Ancel and Bouin have
shown further that there is a parallelism between the development
of the corpus luteum and the growth of the mammary gland in
the rabbit (see below, Chapter XIII.). In the absence of corpora
lutea neither the uterine growth nor the mammary growth take
place.

Although doubt has been expressed by some authors3 as to the
existence of the correlation it has now been abundantly established
by several independent investigators working on different animals.
O'Donoghue4 has confirmed the results for the rabbit's mammary
gland. The development of the mammary tissue in the later part
of pregnancy has been ascribed by Ancel and Bouin to the influence

1 Kleinhaus and Schenk, " Experimentales zur Frage nach der Funktion
des Corpus Luteum," Zeiisch. f. (jfeb. u. Gyniik., vol. Ixi., 1907.

* Ancel and Bouin, " Sur la Fonction des Corps jaunes," C. R. de la >SV. de
Biol., vol. Ixvi., 1909 ; " Le Developpement de la Glande Mammaire pendant
la Gestation est determine par le Corps jaune," C. R. de la Soc. de Biol.,
vol. Ixvii., 1909; "Sur les Fonctions du Corp Jaune Gestatif," Jour.
J'/tt/s. et Path. Gen., vols. xii. and, xiii., 1910 and 1911. (For myometrical
gland see also C. R. de la Soc. de Biol., vol. Ixxii., 1912; and C. R. Acad.
Sci., vol. cliv., 1912 ; and see below, Chapter XIII., for further account and
references.)

3 Dubreuil and Regaud, "Sur les Relations fonctionellea des Corps jaunes
avec PUterus non gravide," I., II., III., and IV., C. R. de la Soc. de Biol., vol. Ixvii.,
1909. See also earlier papers in vol. Ixv., 1908, and vol. Ixvi., 1909. Niskoubina,
on the other hand, tends to confirm Ancel and Bouin, "Recherches experi-
mentales sur la Fonction des Corps jaunes," C, R. de la A'oc. de J3iol.t vol. Ixvi.,
1909.

4 O'Donoghue, " The Artificial Production of Corpora Lutea," Proc. Phys.
Soc., Jour, of Pht/siol., vol. xlvi., 1913.

372 THE PHYSIOLOGY OF REPRODUCTION

of the myometrial gland (see below, p. 618), but Hammond1 has
shown that it is far more likely to be due to the continued influence of
the corpora lutea, depending upon the presence of the foetus, since
these organs do not attain the same dimensions under the experi-
mental condition (which may be called pseudo-pregnancy, a condition
not normally occurring in the rabbit, which usually only has corpora
lutea associated with pregnancy, since it does not ovulate without
copulation). According to Hammond, the corpora lutea do not
degenerate in the later part of pregnancy, and consequently »the
corpora lutea of pseudo-pregnancy in the rabbit are comparable to
the corpora lutea spuria of most other Mammals, although it would
seem probable that, when produced, they persist for a longer time
and exert a greater influence than the " false " corpora lutea of those
polyo3strous animals which ovulate spontaneously. Milk may be
expressed from the glands towards the end of the pseudo-pregnant
period even in rabbits which have only copulated once, having
previously been virgins. The uterine hypertrophy occurring under
the influence of the corpus luteum formed after sterile coition has
been shown to be very pronounced in the rabbit, while the blood
extravasation towards the end of pseudo-pregnancy is also marked 2
(see above, p. 101).

Lastly, it has been found that rabbits which had been pseudo-
pregnant will pluck their breasts and prepare a nest for young
although there were none to be born (see below, p. 576).

In the marsupial cat (Dasyurus) there is only one kind of corpus
luteum 3 (that of pregnancy or pseudo-pregnancy), and the changes
which occur in the mammary glands as a result of luteal influence
are identical irrespectively of whether gestation occurs or not. The
uterine changes are in a general way similar to those occurring under
artificial pseudo-pregnancy in the rabbit.4

Leo Loeb 5 has shown that in the non-pregnant giiinea-pig there
is a definite cycle for the mammary gland and that it corresponds
with the ovarian and uterine cycles. The gland tissue proliferates
when a new ovulation is imminent and to a greater extent later in
the cycle as a result probably of the cumulative influence of the

1 Hammond, " On the Causes Responsible for the Developmental Progress
of the Mammary Glands, etc.," Proc. Roy. Soc., B., vol. Ixxxix., 1916.

2 Hammond and Marshall, "The Functional Correlation between the
Ovaries, Uterus, and Mammary Glands," Proc. Roy. Soc., B., vol. Ixxxvii., 1914.

3 Hill and O'Donoghue, "The Reproductive Cycle in the Marsupial Dasyurus,"
Quar. Jour. Micr. Science, vol. lix., 1913.

4 Retterer and Voronoff (C. R. de la Soc. de Biol., vol. Ixxxiv., 1921) record
growth of uterine glands and cotyledons in goats and sheep through an ovarian
graft containing a corpus luteum and after previous ovariotomy.

5 Loeb and Hesselberg, " The Cyclic Changes in the Mammary Gland under
Normal and Pathological Conditions," Jour, of Exp. Med., vol. xxv., 1917 ; see
also Biol. Bull., vol. xxvii., 1914.

THE TESTICLE AND THE -OVARY 373

corpora lutea. Extirpation of the corpora hitea was followed (see
below, p. 620, Chapter XIII.) by an arresting effect, and by an
acceleration of the next ovulation.1 As long as the corpora function-
ate the presence of mature follicles does not produce those uterine
changes which are characteristic of heat.

In polycestrous animals the corpus luteum spurium usually
degenerates after a short period so as to make way for the
maturation of new follicles and the process of ovulation at the
frequently recurring oestrous periods. Otherwise the ripening
follicles degenerate under the influence of the corpus luteum. Thus
follicular atrophy occurs in widening circles around the corpus
luteum of Dasyurus. The more rapid degeneration of the corpus
luteum spurium has probably taken place in association with the
acquirement of the polyoestrous habit since it would be detrimental
to fecundity if these structures persisted for as long a time as the
corpora lutea of pregnancy.

In moncestrous animals, on the other hand, the persistence of the
corpus luteum spurium over a period equal to that of pregnancy
would not tend towards infecundity, and this probably accounts for
the condition found in the dog.2 Keller3 was the first to describe the
post-oestrous hyperplasia in the uterine glands and the retrogressive
stage which follows, observations which have since been confirmed
and extended. The epithelium of the glands, after being first
columnar afterwards becomes cubical, and in the retrogressive stage
the lumina contain a colloid and sometimes desquamated cells.
There is much haemorrhage in the stroma. Retrogression sets in
about thirty days after ovulation, the mammary glands going through
a similar cycle, growth being followed by a secretion of fluid which
may be identical with milk. These changes occur in \3orrelation
with the growth and degeneration of corpora lutea (see above,
Chapter III., p. 99).

The corpus luteum in polyoestrous animals is known sometimes
to persist for an abnormal length of time, and according to Williams
may be a cause of long-continued sterility. Why the organ 'should
persist is not clear, but Williams 4 states that this condition occurs
most frequently in young cows or heifers which have suffered
some time previously froin contagious granular vaginitis. In certain

1 Excision of corpora lutea in pregnancy, while promoting ovulation, is not
followed by a new uterine cycle, as during pregnancy a mechanism is at work
preventing the uterus from responding to stimuli given off by the ovary (Loeb).

2 Marshall and Hainan, "On the Post-CEstrous Changes occurring in
Generative Organs and Mammary Glands of the Non-Pregnant Dog," Proc.
Roy. Soc., B., vol. Ixxxix., 1917.

3 Keller, " Ueber den Bau des Endometrium beim Hunde," Anat. Hefte,
vol. cxvaii., 1909.

4 Williams (W. L.), Veterinary Obstetrics, New York, 1917.

374 THE PHYSIOLOGY OF REPRODUCTION

cows oestrus is said to take place in spite of there being a corpus
luteum present, but when this is so the periods are shortened to
twelve or fifteen hours instead of the normal duration which is
said to be double that time, and the cows if served in this condition
fail to conceive. It is probable that in spite of oestrus taking place
ovulation fails to occur. The continuance of the corpus luteum
as an apparent result of vaginitis or venereal disease may be due to
the irritation of the generative organs, and is perhaps comparable
to the normal stimulus set up by pregnancy, which results in the
persistence of the corpus luteum in polycestrous as in moncestrous
animals, or to the mechanical and artificial stimuli induced by Leo
Loeb in the uterus of the guinea-pig, which is followed not only by
the formation of decidual cells at the place where irritation is
experienced, but by the persistence of the luteal bodies in the ovary.

Williams states that sterility as a result of the persistent corpus
luteum can be remedied by squeezing out this organ from the ovary,
the operation being performed through the rectum or vagina, and
that oestrus recurs within a short time of the corpus luteum being
eliminated. According to the clinical records of the New York
State Veterinary College, at Cornell University ninety-five per cent,
of the cattle so treated conceived at the first subsequent service.
Albrechtsen,1 however, throws some doubt on the practical value
of this method of treatment. Hess,2 on the other hand, records a
number of observations and experiments which are confirmatory of
those of Williams.

According to Loeb,3 deciduomata (i.e. nodules having the structure
of decidua) can be produced experimentally in the uterine mucosa
of the guinea-pig by making a number of transverse and longitudinal
cuts so as to break the continuity of the tissue. The nodules
originate through a proliferation of the interglandular connective
tissue. Loeb states further that this can only happen during a
certain definite period after the occurrence of copulation or heat.
The changes cannot be induced on the first day after heat, nor after
the tenth day, but deciduomata are readily formed between the third
or fourth and eighth or ninth days. The uterus is therefore most
responsive when freshly formed corpora lutea are present in the
ovaries and therefore at a different time from that at which the
proliferating effect on the mammary gland is produced (see pp. 619

1 Albrechtsen, The Sterility of Cows, English Translation, Chicago, 1917.

2 Hess, Die Sterilittit des Rindes, ihre Erkennung und Behandlung, Hannover,
1921. Cf. also Oppermann, Sterilitat der ffauxtiere, Hannover, 1922.

3 Loeb (L ), "The Production of Deciduomata, and the Relation between
the Ovaries and the Formation of the Decidua," Jour. Amer. Med. Assoc., vol. 1.,
(6th June) 1908 ; Medical Record, vol. Ixxvii., (25th June) 1910 ; Arch, fur
Entwick.-Mech., vol. xxxii., 1911 ; Surgery, Obstetrics, and Gynecology, vol. xxv.,
1917 ; and Jour. E.vp. Med., vol. xxv., 1917.

THE TESTICLE AND THE OVARY

375

and 620). The changes were not excited by the presence of ova in
the uterus, since they took place when the lower part of that organ
was ligatured off so as to prevent the passage of the ova. On the
other hand, if the ovaries were extirpated deciduomata could not be
produced. If the corpora lutea were as far as possible burnt out
of the ovaries by the electric cautery, deciduomata were not generally

FIG. 97. — Experimentally produced placenta of pseudo-pregnant rabbit ; section
of uterus showing connective tissue forming decidual cells which enclose
vessels. (From Hammond:)

produced ; but owing to the difficulty of properly performing these
experiments, the results were not quite conclusive. Lastly, when
pieces of uterus were transplanted into the subcutaneous tissue,
deciduomata were formed in the grafted pieces. It is concluded,
therefore, that the ovaries at certain periods after ovulation (and
probably the corpora lutea) elaborate a predisposing substance in the
presence of which indifferent stimuli (traumatisms) may produce
deciduomata. Hammond has obtained similar results with rabbits.1

1 Hammond, loc. cit.

376 THE PHYSIOLOGY OF REPRODUCTION

It has been shown that the uterine mucosa undergoes atrophy
after the complete removal of the ovaries, and it seems hardly
probable that this process can be arrested by the presence of a
fertilised ovum in the early stages of pregnancy. On the other
hand, it is scarcely conceivable that an ovum could become attached
to a uterine mucous membrane which was in process of degenerating.
It would appear, however, that in the latter half or two-thirds of
pregnancy, when the uterus has already undergone great hypertrophy,
the presence of the ovaries may be dispensed with.1 Furthermore,
it has just been mentioned that the maternal placenta undergoes a
partial degeneration in the later stages of embryonic development.

Miss Lane-Claypon 2 has shown that the interstitial cells of the
ovarian stroma undergo an increase in size during the period of
gestation, but this increase is not so great as that of the luteal cells.
Consequently, she suggests that these cells also may produce a
secretion of the nature postulated for the cells of the corpus luteum.
If this is so, the circumstance that the interstitial cells do not
hypertrophy to the same extent as the luteal cells may perhaps be
ascribed to the different conditions of mechanical pressure existing
in the ovarian stroma.

THE SUPPOSED INTERNAL SECRETION OF THE UTERUS

Although the bulk of evidence obtained clinically points to the
conclusion that the uterine functions fall into abeyance after the
extirpation of the ovaries, while the relatively few exceptions to this
rule are probably to be explained on the supposition of incomplete
removal, some surgeons and gynaecologists have adopted the view
that the uterus is capable of functional activity independently of the
ovaries. A few writers have even • gone further, and have affirmed
the belief that the ovarian functions themselves are dependent upon
uterine influence.

Zweifel and Abel,3 in describing the after-histories of cases of
hysterectomy, stated that, in their experience, when the whole of the
uterus was removed, entire atrophy of the ovaries always followed,
so that menopause symptoms set in similar to those occurring after
ovariotomy. In those cases, however, in which a portion of the
uterine mucous membrane was conserved, menstruation continued
and there were no menopause symptoms. Consequently, these

1 It has yet to be proved, however, that the further course of development
is absolutely normal after ovariotomy in the later part of pregnancy.

2 Lane-Claypon, " On the Origin and Life-History of the Interstitial Cells
of the Ovary of the Rabbit," Proc. Roy. Soc., B., vol. Ixxvii., 1905.

3 Zweifel, Deutsche Gesellschaft fiir Gynakologie in Berlin, ZentraL f.
Gt/nak., No. 21, 1899. Abel, " Dauererf olge der Zweifelschen Myomektoniie,"
Arch. f. Gyiiak., vol. Ivii., 1899.

THE TESTICLE AND THE OVARY 377

surgeons have advocated the operation of sub-total hysterectomy
wherever possible in preference to complete removal, believing that
the functional activity of the ovary is in some way dependent on the
presence of the uterus.

Doran,1 in tracing the after-histories of sixty cases of sub-total
hysterectomy, is disposed to concur with Zweifel and Abel in advising
that the uterus should be removed above the cervix. In support of
this contention he cites two cases in which menstruation persisted
after the removal of the body of the uterus, the cervix being left
behind. In a later paper2 he mentions four cases in which both
ovaries were removed and the menopause was neither immediate nor
complete. He records forty additional cases of sub-total hysterec-
tomy, with after-histories, making a hundred in all.

Mandl and Biirger,3 in a monograph dealing with the subject,
express the belief that in those cases in which the ovaries are
conserved after hysterectomy there is a gradual cessation of function
on the part of these organs, resulting from their degeneration.

Holzbach,4 on the other hand, states that as a rule the ovaries do
not atrophy after hysterectomy, and that, when such degeneration
does occur, it is probably due to interference with the nervous
connections consequent upon the operation of removal.

Graves5 states that after hysterectomy vasomotor disturbances
ensue with approximately equal frequency whether the ovaries be
retained in situ, totally oblated, or transplanted. Retention of
ovarian tissue after removal of the uterus is said to be of little or no
physiological value and may even be productive of serious trouble
to the patient owing to the formation of cysts or adhesions.

Blair Bell6 once suggested that menstruation was brought about
by an internal secretion of the uterus, while he supposed ovulation
to depend on the circulation of this secretion, which he called
" uterine."

Bond" has put forward the view that the ovarian secretion is
influenced by a saline secretion from the anoestrous uterus, the two,
however, acting antagonistically to one another, so that the prevention
of the uterine secretion by hysterectomy favours the hypertrophy of

1 Doran, "Sub-total Hysterectomy for Fibroids," Lancet, Part II., November
1905.

- Doran, "Sub-total Hysterectomy for Fibromyoma Uteri," Proc. Roy. Soc.
Med., (February) 1911 ; Lancet, vol. clxxx., (14th Jan.) 1911.

3 Mandl and Burger, Die Biologische Bedeutung der Eierstocke nach Entfernung
der Gebarmutter, Leipzig, 1904.

4 Holzbach, " Ueber die Function der nach Totalextirpation des Uterus
zuriickgelassenen Ovarien," Arch.f. (tt/nak., vol. Ixxx., 1906.

5 Graves, " Retention of Ovarian Tissue after Hysterectomy," Surg., Gynec.
and Obstet., vol. xxv., 1917.

0 Blair Bell, loc. cit. But cf. The Sex Complex, London, 1916.
7 Bond, "Some Points in Uterine and Ovarian Physiology and Pathology
in Rabbits," lint. Med. Jour., Part II., July 1906.

378 THE PHYSIOLOGY OF REPRODUCTION

the ovaries. Bond's view, therefore, is diametrically opposed to that
formerly held by Blair Bell.

Bond records two experiments on the results of hysterectomy in
rabbits. In one the entire uterus was removed and the animal killed
after five months. Both ovaries were found to be normal. In the
other experiment the left uterine cornu only was extirpated, and the
rabbit was killed after five months. In this case also the ovaries
showed no signs of degeneration. As a result of these experiments
Bond affirms that the prevention of the saline secretion of the uterine
mucosa by previous hysterectomy favours the overgrowth of luteal
tissue in the ovary.

Stress has been laid by various writers upon the well-known fact
that whereas the corpora lutea of the ovary continue to grow for a
considerable period of time if pregnancy supervenes after ovulation,
this hypertrophy soon ceases in the absence of pregnancy. Bond
records an experiment upon a rabbit in which one of the ovaries,
after transplantation in an abnormal position, was found to contain a
somewhat aberrant " corpus luteuin of pregnancy " in association with
a gravid uterus. Such observations are regarded by him as supplying
evidence of an internal uterine secretion acting on the ovaries and so
exciting a growth of luteal tis3ue. This secretion is supposed by
Bond to be quite different from the saline fluid elaborated by the
anoestrous uterus.1 It must be remembered, however, that pregnancy
produces a profound influence over the entire organism, and not
merely over the ovaries ; also that, as recorded above, corpora lutea
are formed habitually in the rabbit's ovaries after sterile coition and
develop during a pseudo-pregnant period.

Certain other authors, such as Loewenthal,2 have suggested
theories which imply a dependence on the part of the ovaries upon
some function of the uterus ; but, excepting for the two experiments
of Bond referred to above, and a series of experiments undertaken
by the author in collaboration with Mr. Carmichael,3 no systematic
investigation ever appears to have been attempted until very
recently upon the effects of hysterectomy.

In our experiments we removed the uterus, either entirely or
leaving only the cervix, from a number of very young immature
rabbits. The animals were killed after they had become fully grown
—in some cases not until ten months after the operation. In every
experiment the ovaries were found to have developed normally. In
some cases, also, copulation was observed on the rabbits being put

1 Bond, "Certain Undescribed Features in the Secretory Activity of the
Uterus and Fallopian Tubes," Jour. Physiol., vol. xxii., 1898.

2 Loewenthal, "Eine neue Deutung des Menstruation process," Arch. f.
nal:, vol. xxiv., 1884.

3 Carmichael and Marshall, Proa. Rot/. <SV-., loc. cit.

THE TESTICLE AND THE OVARY 379

with the buck. Many of the ovaries contained typical corpora lutea,
showing that ovulation had taken place. Also in four experiments
on fully grown rats hysterectomy was performed, and the animals
were killed several months subsequently. The ovaries in no instance
showed any indications of atrophy. On the other hand, marked
uterine degeneration was observed in rats after the removal of the
ovaries for shorter periods of time.1

As a result of these experiments, it may be concluded that the
growth and development of the ovaries is in no way dependent upon
the presence of the uterus. Such a conclusion is no doubt opposed
by some of the clinical evidence, but it is one which was to be
expected on phylogenetic grounds, since the uterus is an organ which
came into existence comparatively recently in the course of vertebrate
evolution, whereas the ovary is common to all Metazoa. It is
possible, in those surgical cases in which the ovaries underwent
atrophy after the removal of the uterus, that this was due to
vascular interference.2

THE COKRELATION BETWEEN THE GENERATIVE ORGANS AND THE
DUCTLESS GLANDS 3

The Thy aim. — Noel Paton4 and Henderson5 have stated that
there is a reciprocal relation between the thymus and the testis, each
checking the growth of the other. This conclusion is based on a
series of observations on cattle and guinea-pigs. In the former it
was found that castration delayed the onset of the atrophy of the
thymus, for the average weight of that organ in bulls up to three and
a quarter years old was considerably less than that in oxen. In
guinea-pigs Paton states that in those animals in which the thymus
was removed at a time prior to the normal period of atrophy for that

1 Marshall and Jolly, " Results of Removal and Transplantation of Ovaries,"
Trans. Roy. Son. Edin., vol. xlv., 1907.

2 Boston has recorded four cases of women where the uterus was congenitally
absent, but in whom the development of the breasts and other changes relating
to puberty excepting menstruation were experienced. Sentiment, sexual desire,
and sexual sensation are stated to have been normal in each case ("Absence
of the Uterus in Three Sisters and Two Cousins," Lancet, Part I., January 1907).
It may also be mentioned that Sellheim found that removal of the oviducts in
pheasants does not result in a shrivelling up of the ovaries and the assumption
of secondary male characters as has been stated (Zeitsch. f. Gynak., 1904, No. 24).
It has not been determined whether the generative organs (apart from the
uterus) undergo the characteristic procestrous changes after hysterectomy, since
these changes are comparatively slight and difficult to detect in rabbits.

3 For a symposium on the relation of the organs of internal secretion to
obstetrics and gynaecology, see Surgery, Obstetrics and Gynecology, vol. xxv.,
September 1917. See also Blair Bell, The Sex Co>n,ple.r, London, 1916.

4 Paton, "The Relationship of the Thymus to the Sexual Organs," Jour, of
Physiol., vol. xxxii., 1904.

5 Henderson, " On the Relationship of the Thymus to the Sexual Organs,"
Jour, of Physiol., vol. xxxi., 1904.

380 THE PHYSIOLOGY OF REPRODUCTION

organ, there was an increase in the growth of the testis. On the
other hand, Soli l states that extirpation of the thymus, carried out in
young rabbits, guinea-pigs, and fowls, caused inhibition of testicular
development, and sometimes even complete arrest of growth by
that organ.

Lucieii and Parisot ~ also found some arrest in the growth of the
testes after thymectomy in the rabbit. Klose and Vogt,3 who worked
on dogs, reported hyperplasia of the testes followed by atrophic
changes. They also describe thyrnectomy as producing a softening of
the bones or a retardation of the growth of the bony tissues, besides
other pathological phenomena. Similar changes are recorded by
Matti,4 who was, however, unable to find any relation between
thymectomy and the time of sperrnatogenesis. Pappenheimer,5 work-
ing upon rats, obtained no evidence of thymectomy having any effect
upon spermatogenesis or the weight of the testes.

As a result of a further series of experiments Paton c concluded
that the thymus and testes do not act antagonistically to one another,
but that each organ has a stimulating effect upon growth, the one organ
compensating for the removal of the other by undergoing hyper-
trophy, whereas neither castration nor thymectomy alone had any
influence upon growth. The double operation upon young guinea-
pigs checked growth.

Mr. Hainan and the present writer,7 in a series of experiments
upon guinea-pigs, while confirming the castration effect upon the
thymus, failed to obtain evidence of the thymectomy effect either
upon growth or upon the testes ; we found further that simultaneous
removal of the testes and thymus did not influence growth. Our
results, as well as those of Paton, were analysed by Udny Yule, who
concluded that Paton's thymectomy results may have been due to
chance variation.

According to Hewer8 it is possible to induce a hyperthymic

1 Soli, "Contribution a la Connaissance de la Formation du Thymus chez
le Poulet et chez quelques Mammiferes," Arch. Ital. de Biol., vol. Ixii., 1909.

2 Lucien and Parisot, "Variation ponderale consecutive a la Thyrnectomie
chez le Lapin," C. R. de la Soc. de BioL, vol. Ixv., 1918.

3 Klose and Vogt, " Klinik und Biologic der Thymusdruse," Beitr. z. kl. Chir.,
vol. xcii., 1910.

4 Matti, " Untersuchung ueber die Wirkung experimentellen Ausshaltung
d. Thymusdruse," Grenzgeb. d. Med. u. Chir., vol. xxiv., 1912.

5 Pappenheimer, "The Thymus Gland, etc., and the Female Genital Tract,"
Surg., Obstet. and Gyn., vol. xxv., 1916. This paper contains many references.

e Paton, "The Thymus and Sexual Organs," Jour, of P/iysiol., vol. xlii.,
1911. .

7 Hainan and Marshall, "On the Eolation between the Thymus and
Generative Organs, etc.," with a Note by Udny Yule, Proc. Roy. Soc., B.,
vol. Ixxxviii., 1914.

8 Hewer, "The Effect of Thymus Feeding, etc.," Jour, of Physiol., vol. xlvii.,
1914 ; "The Direct and Indirect Effect of X-Eays on the Thymus Gland and
Reproductive Organs," Jour, of Physiol., vol. 1., 1916.

THE TESTICLE AND THE OVARY 381

condition in young rats by feeding them upon extract or upon the
fresh gland. Miss Hewer states further that cessation of spermato-
genesis or testicular atrophy is an accompaniment .of this condition.
Moreover, irradiation of the thymus region with X-rays is said to be
followed by degenerative changes in the testes, and irradiation of the
gonads by the appearance of Hassal's corpuscles and other hyper-
trophic changes in the thymus. The data do not, however, appear to
have been large enough or definite enough to warrant the deduction
of precise conclusions.

On the other hand, there can be no doubt about the effect of early
castration upon the thymus, the involution of which is markedly
delayed as shown by Calzolari,1 Ranzi and Tandler,2 Gellin,3 Klose
and Vogt,4 Manassini,5 and Squadrini,6 as well as the investigators
already referred to.

Valtorti7 obtained similar results from ovariotomy in young
rabbits, but he also claimed that thymectomy is followed by
degenerative changes in the ovary. The last results would seem
uncertain in view of the frequency of follicular degeneration in
rabbits' ovaries under normal conditions.

Gudernatsch 8 states that tadpoles fed upon thymus extract grew
to an enormous size and postponed undergoing metamorphosis or did
not change into frogs at all.

The Pituitary. — Fichera 9 observed a constant hypertrophy of the
pituitary body (hypophysis) in capons, oxen, buffaloes, and rabbits,
castrated in early life — that is to say, an increase in weight by that
organ as compared with the pituitary glands of other animals of the
same kind, weight, and age. The increase in weight was associated
with a rich blood supply, and an increase in the number of eosinophyl
•cells. These observations are confirmed for young dogs by Cimorini,1(?

1 Calzolari, "Recherches experimentales sur un Rapport probable entre la
Fonction du Thymus et celJe des Testicules," Arch. Ital. de Biol., vol. xxx., 1898.

2 Ranzi and Tandler, "Ueber Thymus Extirpation," Wien. klin. Woc/i.,
vol. xxii., 1909.

3 Gellin, "Die Thymus nach Extirpation, etc.," ' Zeitsch. f. exp. Path, und
Pharm., vol. viii., 1910.

4 Klose and Vogt, " Klinik und Biologic der Thymusdriise," Beitr. zur klin.
Chir., vol. Ixix., 1910.

5 Manassini, " Sur les Modifications que la Castration peut determiner dans
les Organes glandulaires, etc!," Arch. Ital. de Biol., vol. liii., 1910.

(i Squadrini, "II com portamento del timo nelle varie della Vita postpetali
nei Bovini," Pathologica, vol. ii., 1910.

7 Valtorti, "Timo et Ovari," Ann. di Ostct., vol. xxix., 1907, and vol. xxxi.,
1909.

8 Gudernatsch, "Feeding Experiments on Tadpoles," Arch.f. Entivick.-Mech.,
vol. xxxv., 1913, and Amer. Jour, of Anat., vol. xv., 1914.

9 Fichera, "Sulla ipertrofia della glandula Pituitaria consecutiva castrazione,"
Polidinico, vol. xii., 1905.

10 Cimorini, " Sur 1'Hypertrophie de 1'Hypophyse cerebrale chez les Animaux
thyreVidectomises," Arch. Ital. de Bid.., vol. xlviii., 1907.

382 THE PHYSIOLOGY OF REPRODUCTION

who states that the changes in the pituitary were similar to those
occurring after removal of the thyroids. Taiuller and Gross1 have
described pituitary hypertrophy in castrated men. The condition
was found in the Skopzen sect of eunuchs and also in women after
ovariotomy. Hammond 2 has shown that pituitary hypertrophy occurs
in sheep after ovariotomy. It affects the glandular part or anterior
lobe only. Blair Bell 3 finds evidence of increased secretory activity
on the part of the anterior lobe of the pituitary after ovariotomy,
but in his experience the changes are slight and not quite constant.
They are not nearly so great as during pregnancy or after the removal
of the thyroids or suprarenals. According to Livingston4 whereas
ovariotomy may cause hypertrophy of the pituitary in rabbits, the effect
of castration on that organ is negligible. According to Pepere,5 there is
probably no specific hypertrophy of the hypophysis in relation to the
extirpation of any particular ductless gland in the organism, but
the reaction of the cellular elements, though varying in response to
different conditions, shows also many characters referable to a common
cause.

Compte6 showed that the anterior lobe undergoes hypertrophy
during pregnancy, the whole organ being increased in weight at
the end of the period. Erdheim and Stumme7 confirmed and
extended the observations. The changes are due mainly to the
accumulation of the " pregnancy cells " which are derived from the
chromophobe or chief cells. Blair Bell8 regards these pregnancy
cells as being correlated with an immediate demand for increased
secretion. The secretory products appear to pass over, at anyrate to
some extent, to the posterior lobe. Pituitary hypertrophy during
pregnancy may be so great as to cause pressure on the optic chiasma
and transient pathological symptoms which disappear later when the
gland returns to the normal condition.

It has been shown, as will be described more fully in the chapter
on lactation (p. 621), that extract of posterior lobe when injected into

1 Tandler and Gross, "Einfluss der Kastration, etc.," Wien. klin. Woch.,
vol. xx., 1907. Tandler, " Untersuchungen an Skopzen," Wien. klin. Woch.,
vol. xxi., 1908.

2 Hammond, " The Effect of Pituitary Extract on the Secretion of Milk,"
Quar. Jour. Exp. Phys., vol. vi., 1913.

3 Blair Bell, loc. cit.

4 Livingston, " Effect of Castration on Weight of Pituitary in Rabbits,"
Proc. Soc. Exp. Biol. and Med., vol. xi., 1914 ; and Amer. Jour. P'hysioL, vol. xl.,
1916.

5 Pepere, " Sur les Modifications de Structure • du Tissu Parathyroidien
normal et accessoire (thymique) en rapport avec sa Fonction vicariante," Arch,
de Med. Exper., vol. xx., 1908.

6 Compte, Contribution a V Etude de Hypophyse, etc., Lausanne, 1898 ; and
Beitr. zur Path. Anat., etc., vol. xxiii., 1898.

7 Erdheim and Stumme, " Ueber die Schwangenschaftveraenderung der
Hypophyse," Beitr. zur Path. Anat., etc., vol. xlvi., 1909.

* Blair Bell, loc. cit.

THE TESTICLE AND THE OVARY 383

the circulation has an immediate galactogogue effect, milk being
copiously secreted if the mammary glands are in a state of lactation.
The same effect occurs as a result of injecting extract of corpus
luteum. Experiments have shown that ovariotomy . results in
persistent lactation if the operation be performed during the suckling
period (see p. 614). It seems possible, therefore, that after ovariotomy
the function of the corpus luteum in respect of mammary secretion is
taken over by the pituitary vicariously, and that this organ when
hypertrophied (unlike the corpus luteum) continues to exert an
influence upon the mammary activity which may be continued
indefinitely.1

Crowe, Gushing, and Romans,2 as a result of a series of experiments
on hypophysectomy on dogs, have shown that partial removal of the
anterior lobe was followed by hypoplasia of the generative organs or
persistent infantilism if the operation wras done before puberty. ,
There was a tendency to adiposity such as often occurs after castration.
Aschner 3 obtained similar results. Puppies operated upon remained
completely impotent and spermatogenesis did not occur in the male,
neither did ovulation nor O3strus in the female. Hypophysectomy
during pregnancy prevented the further development of the foetus.
Blair Bell found atrophic changes in the ovaries and uterus after
partial removal of the anterior lobe. Clamping the infundibular
stalk caused even more intense atrophy.

Goetsch 4 has obtained converse results by the administration of
pituitary extract (in particular of anterior lobe which he states to be
the responsible factor). Young rats fed with extract showed increased
development and activity of the reproductive organs as compared with
the controls. The Graafian follicles ripened more quickly. The
uterine mucosa developed active glands, and there was increased
vascularity over the whole generative tract. Extract of posterior
lobe had no effect.

Clinical observations point clearly to similar conclusions. Hyper-
pituitarism due to overactivity of the anterior lobe and manifested
histologically by a great increase in the eosinophile or acidophile cells,
if commencing before puberty results in giantism, and if postadolescent
causes acromegaly or an overgrowth of the bones of the face. In the
former case it is associated writh premature sexuality and in the latter

1 This hypothesis assumes a functional connection between the anterior and
posterior lobes (see p. 382).

2 Crowe, Gushing, and Homans, " Experimental Hypophysectomy," Johns
Hopkins Hosp. Bull., vol. xxi., 1910. Gushing, The Pituitary Body and its
Disorders, New York, 1912.

3 Aschner, "Ueber die Funktion der Hypophyse," Pfliigeijs Arch., vol. cxlvi.,
1912.

4 Goetsch, " The Relation of the Pituitary Gland to the Female Generative
Organs," Siirg., (fi/n. and Obstet., vol. xxv., 1917.

384 THE PHYSIOLOGY OF REPRODUCTION

with excessive sexual desire. However, after a period of hyper-
activity on the part of the pituitary, retrogressive changes set in
with that organ, and these are accompanied or followed by impotence
and atrophy in the reproductive organs.1

The Pineal. — Precocious sexual development associated with early
secondary sexual changes (growth of pubic hair, enlargement of larynx,
etc.) and general body growth is said to be correlated with hyperactivity
in the pineal gland, but the evidence is very incomplete. Moreover,
according to M'Cord 2 the administration of pineal extract to young
Mammals is reported to hasten growth and sexual maturity. When
given to unicellular animals (Paramacium) the rate of reprodiiction
was markedly increased, and when fed to tadpoles, growth and
metamorphosis were hastened. On the other hand, according to Biach
and Hulles,3 castration in kittens caused atrophy of the pineal, and
according to Foa 4 removal of the pineal in the young cockerel caused
sexual precocity and an earlier development of the secondary male
characters.

The Thyroid. — It is well known that there is a correlation
between the sexual organs and the thyroids. These glands undergo
enlargement during menstruation and pregnancy in women, and
Freund5 has shown that similar changes occur during the heat
periods of many of the lower Mammals. He has pointed out further,
that swelling of the thyroid, at the time of puberty, often leads to
goitre, ami that this disease commonly begins at a period of menstrua-
tion. M'Carrison ° states that the sexual act and marriage in both
sexes increases the gland's activity and that the consequent swelling
is well known to primitive races. Arbuthnot Lane 7 also says that
swelling is associated with intercourse as well as with pregnancy, and
that it alters with the intensity of the sexual appetite. Such facts
are cited by Gaskell 8 as evidence of a special connection between the
thyroid and the sexual organs— the former being held to represent
the uterus of the scorpion. Alquier and Thauveny 9 state that after
the partial or complete removal of the thyroids and parathyroids

1 See also Woods Hutchinson, "The Pituitary Gland as a Factor in Acrome-
galy and Giantism," New York Med. Jour., 1900.

*- M'Cord, "The Pineal Gland," Hurg., Gt/n. and Obstet., vol. xxv., 1917.

;i Biach and Hulles, " Ueber die Beziehungen cler Zurbeldriise zum Genitale,"
\Yien. klin. Woch., vol. xxv., 1912.

4 -Foa, " Hypertrophie des Testicules et de la Crete apres 1'Extirpation de
la Glande Pineale chez le Coq," Arch. Ital. de Kiol., vol. Ivii., 1912.

•"' Freund, " Die Beziehungen der Schilddriise zu den weiblichen Geschlechts-
organen," Deutsche Zeitsch. f. Chir., vol. xviii., 1883.

" M'Carrison, The Thyroid Gland, London, 1917.

7 Lane, Guy's Hospital Gazette, vol. xxxii., 1918.

* Gaskell, The Origin of Vertebrate*, London, 1908.

9 Alquier and Thauveny, " Kt at de 1'Ovaire de Chiennes ayant 1'Extirpation
partielle ou totale de 1' Apparel 1 Thyro-Parathyroidien," C. R. de la 8oc. de BioL,
vol. Ixvi., 1910.

THE TESTICLE AND THE OVARY 385

menstruation and conception are very infrequent, but this result may
be due to the general metabolic disturbance arising from the absence
of the glands. Blair Bell found that after thyroidectomy in the cat
the uterus underwent atrophy similar to that observed after the
removal of the ovaries. According to the same author there is in
Rodents a considerable increase in the functional activity of the
thyroid in regard to colloid production after ovariotomy. It is stated
also that the colloid is basophile instead of eosinophile and this change
is regarded as representing a storage secretion formed to meet the
altered conditions of metabolism. According to Leo Loeb1 almost
complete thyroidectomy during pregnancy does not always necessarily
lead to abortion, but no hypertrophy was found in the thyroids of the
foetuses.

The Parathyroid. — According to Pool,2 the efficiency of the para-
thyroid is affected by the oestrous cycle, for tetany, which is the clinical
manifestation of parathyroid insufficiency, is especially prone to occur
during menstruation, pregnancy, or the puerperium, when the para-
thyroids fail to adjust themselves to an increased metabolism. Blair
Bell states that castration may prevent tetany in cats from which the
thyroids and most of the parathyroids have been removed, and this
result is ascribed to a retention of calcium. In maternal tetany
calcium in large doses has a beneficial resiilt.

The Suprarenal. — There is some evidence of a correlation existing
between the sexual organs and the suprarenals. Thus Gottschau :5
states that in rabbits changes occur in these organs during pregnancy,
the outer zone of the cortex becoming twice its normal thickness,
whereas the medulla is said to become thinner. Similarly, Stilling4
states that in frogs during the pairing time the medulla dis-
appears, while characteristic cells known as " summer cells " become
developed. Bulloch and Sequeira5 state- that in cases of children
with carcinomata of the suprarenals, this is associated with pre-
mature development of the genital organs and the accessory
generative glands. According to (rlvim,6 adrenal hypernephromata
are generally associated with sexual precocity and overgrowth of
hair in children.

1 Loeb, "Studies on Compensatory Hypertrophy of the Thyroid Gland," I.,
Jour. Med. Research, vol. xl., 1919.

2 Pool, "The Relation of the Parathyroid System to the Female Genital
Apparatus," A'»n/., Gyn. and Obgtet., vol. xxv., 1917.

3 Gottschau, "Ueber Nebennieren der Saiigethiere, etc.," 8itz.-K<>r. </. phi/n.
•med. (resell, zu Wiirzburff, vols. xvii.-xviii., 1882.

4 Stilling, "Zur Anatomie der Nebennieren," Arch. f. Milcr. Annt., vol. lii.,
1898.

" Bulloch and Sequeira, " On the Relation of the Suprarenal Capsules to the
Sexual Organs," Trans. Path. Hoc., vol. Ivi., 1905.

c Glynn, "The Adrenal Cortex, its Rests and Tumours; its Relation to
other Ductless Glands, and especially to Sex," (Jitar. Jour, of Med.t vol. v., 1912.

13

386 THE PHYSIOLOGY OF REPRODUCTION

R G. and A. D. Hoskyns l state that feeding rats on desiccated
suprarenal gland led to the hypertrophy of the gonads.

The evidence as to the effect of castration on the suprarenals is
conflicting.2

It is thus seen that there is evidence of very definite functional
correlation between the gonads and the other organs of internal
secretion. In some cases this appears to be of the nature of a
potential compensatory arrangement ; in others it would seem rather
that the glands act antagonistically. In the present state of our
knowledge it is hardly possible to formulate any general scheme
which embraces all the known facts, and such attempts as have been
made in this direction have in our judgment been premature.3

GENERAL CONCLUSIONS REGARDING THE INTERNAL SECRETIONS
OF THE OVARY AND THE TESTIS '

It will be convenient at this point to summarise the conclusions
which have been tentatively arrived at concerning the nature and
purpose of the internal secretions of the ovary and the testis.

The mammalian ovary, in addition to its oogenetic function, is an
organ elaborating a chemical substance or substances which react on
the general metabolism and control the nutrition of the uterus and,
at any rate to some extent, of the mammary glands. The secretion
is probably produced by the cells of the follicular epithelium, or by the
interstitial cells of the stroma, or, perhaps, by both combined.4 It is
formed in greater or less quantity at all times, but is produced in
increased abundance at certain recurrent periods, when it brings
about those conditions of growth and hyperamiia which characterise

1 Hoskyns (R G.) and Hoskyns (A. D.), "The Effects of Suprarenal Feeding,"
Arch: Int. Med., vol. xvii., 1916.

- See Swale Vincent, "The Experimental and Clinical Evidence as to the
Influence Exerted by the Adrenal' Bodies upon the Genital System," $urg., <!iin.
and Obstet., vol. xxv., 1917. See also de Mira, " Sur 1'etat des Capsules
Surrenales chez les Animaux OvariectomiseX" Bull. <S'oc. Portugaue des tici.
Nat., vol. vi, 1912.

3 See Swale Vincent, Internal Secretion and the Ductless Glands, London,
1922. Noel Paton, The Nervous and Chemical Regulation of Metabolism, London,
1913. Biedl, loc. cit., and Blair Bell, loc. cit.

4 Limon (loc. cit.) suggested, as a result of his experiments in grafting, that
the ovarian secretion is elaborated by the interstitial cells. It should here
be remembered that the follicular epithelial and interstitial cells are almost
certainly identical by origin, and so probably similar potentially (p. 114), and
that both of these cellular elements have been described as taking part in the
formation of the corpus luteum (p. 142) ; and also, that those interstitial cells
which do not form part of the corpus luteum have been stated to undergo an
independent hypertrophy during pregnancy (p. 156) ; cf. Steinach and Lipschiitz
on the "puberty gland" (see above, p. 346). Bucura (foe. cit.) regards the
follicular epithelium, the interstitial cells, and the corpus luteum as alike in
producing sexual hormones.

THE TESTICLE AND THE OVARY 387

the prooestrous processes. It is at these periods also, in typical cases,
that the follicles become mature. After ovulation, which occurs
during cestrus, the secretory cells of the ovary show still greater
activity, and become converted by a process of simple hypertrophy
into the luteal cells of the corpus luteum. If the ovum is fertilised,
these cells continue to increase in size until nearly mid-pregnancy
(or, in some animals, a somewhat earlier period), but later they
undergo degeneration. If pregnancy does not supervene, the luteal
cells in polyoestrous animals under normal conditions begin to
degenerate at a much earlier period and without attaining their full
development. In monoestrous animals the corpus luteum persists for
an approximately equal time under conditions of pregnancy or
pseudo-pregnancy. The pronounced hypertrophy of the follicular
epithelial and interstitial cells, which takes place at the beginning
of pregnancy, is directly correlated witli a nearly simultaneous
hypertrophy on the part of the uterus and of the mammary glands.
The corpus luteum, therefore, is to be regarded as an essential factor
in maintaining the raised nutrition of the uterus during a part at
least of the period of gestation ; it is also responsible for stimulating
the growth of the mammary tissue preparatory to the secretion of
milk. When the later part of gestation is reached, the ovarian
secretion has probably been already formed in sufficient quantity to
prevent the uterus from lapsing into the normal condition until the
end of pregnancy. It is to be noted, however, that fibrous degenera-
tion has been described in the maternal placenta in the later stages
of its existence.

Thus the ovaries pass through a series of cyclical changes which
are directly correlated with those undergone by the uterus and
mammary glands. The ovarian changes are always the cause; the
uterine and mammary changes are the effects. Moreover, the uterus
atrophies after ovariotomy. Whether or not the corpus luteum
(which may persist for a time even after parturition) is a factor in
actual milk secretion is an open question, but the influence of luteal
extract on this process is suggestive of a connection.

It seems probable that this close co-ordination between the
ovarian and uterine functions arose very gradually in evolutionary
history, and it may be that in the aplacental Mammals we have in
existence at the present day an intermediate stage in the development
of this relation. Starling l has suggested that the internal secretions,
or hormones generally, arose at first as products of ordinary metabolic
activity in certain particular tissues, and that the evolution of the
various cases of chemical correlation between different organs in

1 Starling, "The Chemical Co-ordination of the Activities of the Body,"
Science Progress, vol. i., (April) 1907.

388 THE PHYSIOLOGY OF REPRODUCTION

the body came into existence, not by the production on the part of
certain tissues of special substances acting as chemical messengers,
but by the acquisition of a specific sensibility on the part of other
functionally related tissues. It is no doubt possible that the chemical
co-ordination of the ovarian and uterine activities arose partly in this
way ; but, on the other hand, the definite character of certain of the
cyclical changes which take place in the ovary, and particularly those
which relate to the formation of the corpus luteum, points to the
conclusion that the secretory function of the ovary has been perfected,
or at any rate has undergone great development in the phylogenetic
history of the Mammalia, though it no doubt existed previously in
a minor degree.

As to whether the ovary elaborates more than one specific
substance acting as a chemical excitant, there is some evidence,1
and the composition of the corpus luteum (which is different from
that of the rest of the ovary) indicates that the formation of this
structure is accompanied by a change in the nature of the ovarian
secretion. Lastly, it is possible that the influence of the ovary upon
the metabolism is due partly to this organ being excretory as well
as secretory in function, but there is no evidence that this is actually
the case.

The fact that the testis is an organ of internal secretion seems
also to be definitely proved. This secretion is probably formed
throughout the entire reproductive period of an animal's life; but,
in those animals which experience a periodic rut, it is no doubt at
this season that the testicular hormone is produced in greatest
abundance. The development of the prostate and the secondary
sexual characters, not to mention the growth of the testes them-
selves, is convincing evidence that this is so. The hormone is
apparently produced by the interstitial cells (at least in Mammals).

THE INFLUENCE OF THE REPRODUCTIVE ORGANS AND THE EFFECTS
OF CASTRATION UPON THE GENERAL METABOLISM

In view of the facts referred' to above it is almost self-evident
that castration must exercise some influence upon the general
metabolism of the body, since it produces such marked effects upon
the primary and secondary sexual characters. Moreover, it is
commonly believed that the removal of the reproductive glands
causes a tendency towards obesity both in man and animals, but
it is not quite clear whether this occurs as a direct or an indirect
consequence of castration. However this may be it seems certain
that sows which have been spayed fatten faster and thrive better

1 See below, p. 621, Chapter XIII.

THE TESTICLE AND THE OVARY 389

than those left unoperated upon, but this result may be due to their
feeding more regularly and without disturbance from recurrent
(estrous periods.1 The deposition of fat which is so often seen after
the menopause is to be regarded as further evidence of a connection
between the functional ovaries and the general metabolism.

The existence of such a functional correlation is shown more
clearly by the effects of ovariotomy upon the bone disease known
as osteomalacia.2 The ovaries undoubtedly exert a marked influence
over the phosphorus metabolism, and the improvement which sets in
after the removal of these organs in cases of osteomalacia is apparently
brought about by a retention of the earthy phosphates whereby the
skeletal tissues acquire their normal rigidity. Unfortunately, the
experimental work which has so far been done upon the phosphorus
and calcium metabolism in normal and castrated animals is too
contradictory to admit of the deduction of any conclusions that are
calculated to throw much light upon the phenomena of osteomalacia/5
Blair Bell,4 however, records a reduction of fifty per cent, in the
calcium excretion of cats after ovariotomy, and with this he correlates
the fact that in young animals there is generally an increase in
the length of the long bones after ovariotomy, as well as the just
mentioned case of osteomalacia being cured by the same operation.

The protein metabolism of castrated animals has been investigated
by Liithje,5 who records no changes as a consequence of the removal
of the generative glands. Certain other investigators, as a result of
shorter series of experiments, have obtained trifling effects, sometimes
showing a slight increase in the nitrogenous output and sometimes a
diminution.5

Experiments upon the respiratory exchange have been almost
equally inconclusive, and have so far failed to show any constant
alteration as a consequence of castration. This question is discussed
at some length by von Noorden,7 who calls attention to the necessity

1 Mackenzie and Marshall, "Physiology and Bacon Curing," Jour. Roy. Agric.
Soc., vol. Ixxvi., 1915. See also "On Ovariotomy in Sows," Jour. Agric. Soc.,
vols. iv., v., vi., vii., 1911-16.

- In one case of osteomalacia Ki-onig removed the ovaries and transplanted
them on to the peritoneum. The result was immediately beneficial ; but with
the return of menstruation, which followed after about two months, the
symptoms of the disease are said to have reasserted themselves (Stuttgart
Medical Congress, Zeitsch. f. Gyndk., 1906). See also Fraenkel, " Ovarialanti-
korper und Osteomalacia," Munch, med. Wochenschr., No. 25, 1908.

3 Von Noorden, Metabolism and Practical Medicine, English Edition, edited
by Walker Hall, vol. i., London, 1907 (see above, p. 298). According to Wallart,
" TJeber das Verhalten der interstiellen Eierstocksdriise bei Osteomalacia,"
Zeitsch. f. Geb. und Gynak., vol. Ixi., 1908, osteomalacia is correlated with an
increase of the interstitial cells in the ovary.

4 Blair Bell, foe. tit.

5 Liithje, "Ueber die Kastration und ihre Folgen," Experim, Archie,
vol. xlviii., 1902, and vol. 1., 1903.

6 Von Noorden, loc. tit. 7 Ibid.

390 THE PHYSIOLOGY OF REPRODUCTION

for distinguishing whether the total daily metabolism, which in some
cases has been shown to become diminished after castration, does so
in consequence of a variation in temperament (or greater tendency
towards physical repose), or whether the oxidation of the resting cell
(i.e. the fundamental metabolism) is reduced. He is disposed to
believe that the marked diminution in the respiratory exchange
which has been observed in some animals after castration is probably
due to a greater indolence, and is, therefore, an indirect result.
Moreover, he points out that, in the case of Ltithje's castrated dogs,
which did not exhibit any change from their normal habits and
movements, there was no diminution in the gaseous exchange as
compared with control animals.

Loewy and Bichter,1 however, have arrived at different conclusions,
finding pronounced reduction in the respiratory metabolism of castrated
dogs of both sexes. Furthermore, these investigators found that after
feeding the female animals upon ovarian substances there was a great
increase in the metabolism, a castrated bitch showing an increase of
from thirty to fifty per cent, above the normal values observed before
the operation. Testicular substance had no influence upon any of
the castrated animals, while normal animals did not react at all either
to ovarian or to testicular extracts. Loewy and Richter suggest that
the ovaries produce a specific substance which promotes oxidation in
the body.

Zuntz 2 lias investigated the gaseous metabolism in four castrated
women, and found that it lay within the limits of the normal. It is
to be noted that neither of these women showed any tendency to
corpulence. These observations support the view that when castrated
animals show a reduction in the respiratory exchange, this is an
indirect effect resulting from greater indolence of disposition. On
this view, also, the tendency towards a deposition of fat on the
part of many castrated animals is to be attributed to the same
cause.

Dr. Cramer,3 working in conjunction with the author, has lately
investigated the respiratory metabolism of a number of rats whose
ovaries had been removed some time previously, and in these animals
it was found that the gaseous exchange lay within the limits of the
normal, thus confirming Zuntz's experience with castrated women.
It is possible, however, that the results of castration were obscured
by other factors. In this investigation the apparatus employed by
Haldane and Pembrey was used in preference to that of Zuntz. We

1 Loewy and Richter, " Sexual-Funktion und Stoffwechsel," Arch.f. Physiol.,
Supplement, 1899.

2 Zuntz, "Gaswechsel bei Kastrierten Frauen," Yerhandl. d. Gynak. Getell.,
Berlin, 1904. See also Deutsch. Zeitsch. f. Chir., vol. 65, 1908.

3 Cramer and Marshall. MS. unpublished.

THE TESTICLE AND THE OVARY 391

i

did uot observe any marked tendency to deposition of fat in the
castrated rats.

Furthermore, it is to be noted that, according to Magnus-Levy
and Falk,1 the period of puberty in boys and girls is not associated
with any increase in the gaseous metabolism.

Murlin and Bailey,2 however, obtained results upholding those of
Loewy and Richter so far as the reduction in metabolism after
castration is concerned. .Ovariotomy in dogs was followed by an
increase in weight and an average lowering of the metabolism of
about twelve per cent. The animals were fed on a, constant diet
of meat, cracker meal, and lard. The metabolism was estimated by
an indirect method, using Murlin's constant temperature respiration
incubator and weighing the oxygen entering and the carbon dioxide
and water leaving the box. A sample of the residual air of the
cage was also weighed at the end of each period. The urine was
analysed for nitrogen and the amount included in the result.

Moreover, Kojima3 states that twenty-two and forty-eight days
after castration in rats the animals showed a marked diminution in
C02 output. The appetite and weight increased.

Certain further experiments upon the effects of administering
ovarian extract may also be referred to here. Neumann and Vas 4
record losses of nitrogen, phosphorus pentoxide, and calcium monoxide
after injecting glycerine extract of ovary subcutaneously. Loewy5 and
Neumann found no change in the nitrogen metabolism in castrated
animals after administering ovarian extracts, but Neumann observed
a loss of phosphorus pentoxide and calcium monoxide in the faeces.
Sack6 found that injection of corpus luteum extract produced a
nitrogen retention in the female, but not in the male, thereby con-
firming the view that the corpus luteum must act 011 the uterus, or
mammary gland, or both. Certain other less satisfactory experiments,
dealing with more or less contradictory observations, are briefly
referred to by von Noorden.

Mackenzie Wallis and Everard Williams7 have recently carried out
what appears to be a very important investigation upon the corpus

1 Magnus-Levy and Falk, " Lungengaswechsel des Menschen," Arch. f.
Physiol., Supplement, 1899.

2 Murlin and Bailey, "Relation of the Sex Glands to Metabolism," Surg.,
Gyn. and Obstet., vol. xxv., 1917.

3 Kojima, " Studies on the Endocrine Glands," V., Qiutr. Jour. Exp. Physiol.,
vol. xi., 1917.

4 Neumann and Vas, " Einfluss der Ovariumpraparate auf den Stoft'wechsel,"
Monatsschr. f. Geburtsh. u. Gyniik., vol. xv., 1902.

5 Loewy, "Ueber den Einfluss des Oophorins," Berl. klin. Wockenschr., 1899.
0 Sack, " Ueber den Einfluss von Corpus Luteum und Hypophyse auf den

Stoffwechsel,;' Arch. fur. Exp. Path, und Pharm., vol. Ixx., 1912.

7 Wallis and Williams, " An Experimental Investigation upon the Corpus
Luteum in Relation to the Toxaemias of Pregnancy," Lmicet, vol. ccii.,
(22nd April) 1922.

392 THE PHYSIOLOGY OF REPRODUCTION

luteum in relation to the toxemias of pregnancy. By alcoholic
extraction from the fresh gland obtained from the ovaries of sows
and in some cases from women, they have prepared and isolated
a chemical substance which, when injected into animals, produces
necrosis and other changes similar to the toxaemias. Extracts of
placenta and of hydatiform mole, on the other hand, were found to
be non-toxic. The authors believe that the toxaemias which so
often occur in pregnancy are due to hyperactivity of the corpus
luteum, and they suggest further that it is the secretion from this
organ which reacts on the thyroid and stimulates it to growth and
hyperactivity. The excess of cholesterol during pregnancy is
regarded also as an attempt to neutralise the toxic effect of the
corpus luteum. The active principle was protein free, but it appeared
to be associated with a lipoid. Cholesterol, choline, histamine, and
tyramine were absent. " The highly refractile solution was found
to undergo destruction with the serum of a pregnant woman." The
test was likewise positive during the early stages of menstruation,
but otherwise with non-pregnant women it was negative, as it was
also with males. The changes were observed by means of the
refractometer.

The influence of castration upon the blood has formed the subject
of a research by Breuer and Seiler,1 who employed bitches whose
ovaries were removed shortly after puberty. They record marked
diminution in the haemoglobin and the red cells.2

In concluding this brief summary of the recorded results of
castration, and the influence of the generative organs upon the
metabolism, the necessity for further investigation must be em-
phasised, since it is hardly possible that the totality of the effects
produced is of as slight a nature as the accepted evidence at present
seems to indicate.3

1 Breuer and Seiler, "Einfluss der Kastration auf den Blutbefund weiblicher
Tiere," Experim. Archiv, vol. 1., 1903.

- It has also been stated that castration may improve the quality of the
milk (Oceanu and Babes, " Les Effets Physiologiques de POvariotomie chez la
Chevre," C. R. de VAcad. des Sciences, vol. cxl., 1905). For some account of
the effects of disease in the ovaries and other reproductive organs upon the
rest of the body, see Wilson, " The Reciprocal Relations between the Affections
of the Uterus and its Appendages upon the Rest of the Body " (Lancet, Part II.,
November 1906). further references are given in this paper.

3 For a full bibliography see Barker, Endocrinology and Metabolism, New
York and London, 1922. For further experimental wo'rk on sexual characters
see Zawadowsky, Das (Jeschleclit und die Entwickehing das geschlechtmerkmale,
Moscow, 1922. (The work is written in Russian.)

It has been found that ovariotomy performed in young Herdwick lambs
does not result in horn growth, though in one animal small scurs were formed ;
such scurs are said, however, sometimes to occur normally in Herdwick ewes
(Marshall, Proc. Roy. Soc., B., vol. Ixxxv., 1912 ; ef. p. 323 above).

CHAPTER X1
FOETAL NUTRITION: THE PLACENTA

"Birth ... is commonly considered as the point at which we begin to
live. More truly it is the point at which we leave off knowing how to live.
. . . Not but what before birth there have been unsettled convictions (niore's
the pity) with not a few." — SAMUEL BUTLER.

PART I

THE PLACENTA AS AN ORGAN OF NUTRITION

I. HISTORICAL SURVEY

THE mammalian ovum, in all except the Monotremata, is small and
does not contain a sufficient supply of nutriment for the developing
embryo. It is retained for a longer or shorter period in the uterus,
where, by special modifications of the uterine mucosa and a part of
the ovum, the placenta is formed, and a transmission of nutriment
from the mother to the embryo is made possible. The changes in the
maternal and embryonic tissues vary greatly in the several orders,
and even in groups of the same order, but in all they are sufficiently
complicated to render their explanation a matter of great difficulty.
It is doubtful if any anatomical structure has given rise to keener or
more prolonged controversies than the placenta.

We owe to Harvey 2 the conception of the placenta as an organ
elaborating from the maternal blood the aliment necessary for the
growth and development of the tetus. He was the first to reject
the " subtleties and fanciful conjectures " on embryonic development,
and to advocate and practise direct and diligent observation. ' But
for a century after his death the placenta received little notice.
With the introduction of the microscope the attention of biologists
was directed towards the origin and development of the embryo, and
it was then that the ovarian vesicles and spermatozoa were first
observed.

In the second half of the eighteenth century were published the
researches of John and William Hunter on. the human placenta,
important not only in themselves, but as destined to set agoiug the

1 By James Lochhead.

2 Harvey, The Generation of Animals, London, 1651.

13 A 393

394 THE PHYSIOLOGY OF REPRODUCTION

vast amount of work done in the first half of the nineteenth century.
John Hunter l stated that the maternal blood circulated through the
placenta, and this view, which, according to Waldeyer,2 had formerly
been held by Yater and Noortwyk, though the latter at least believed
in the communication of the maternal and foetal circulations, was
supported by the subsequent dissection of injected placentae by
John Hunter and his brother. The statement of the former that
" the blood of the placenta is detached from the common circulation
of the mother, moves through the placenta, and is then returned
back into the circulation of the mother," gave rise later to a consider-
able amount of discussion. They showed that the decidua was uterine
and not foatal, and the decidua reflexa was first figured in one of
William Hunter's plates.3

It is remarkable that John Hunter did not recognise the placenta
as the organ of foetal respiration. A century before, Mayow4 had
declared that the placenta functioned as a foetal lung, the umbilical
vessels taking up the nitro-aerial gas (oxygen) and carrying it to the
foatift. This view was adopted by Ray,5 who compared the villi lying
in the maternal sinuses to the gills of a fish in the water. The first
to take up Priestley's discovery of oxygen, and state definitely that it
was oxygen that went constantly from mother to foatus, and whose
absence caused foetal asphyxia, was Girtanner in 1794. But all
doubt was not removed till, in 1874, the spectroscopic bands of
oxyhsemoglobin were demonstrated in the umbilical vein of a guinea-
pig by Albert Schmidt, a pupil of Preyer.6

The work of the brothers Hunter was carried on by Weber,.
Goodsir, Coste, Eschricht, Reid, and others. Of the many investiga-
tions, none had such an important influence as the researches of
Goodsir.7 He first studied the placental cells with regard to their
function, His predecessors had spoken in the vaguest terms of the
passage of nutriment from mother to foetus, but Goodsir had definite
ideas. He described the villi as having two covering layers of cells,
an external system belonging to the decidua, and an internal belonging
to the chorion. As to their function, he says : " The external cells
separate from the blood of the mother the matter destined for the
blood of the foetus they are secreting ; the internal cells absorb the
matter secreted by the agency of the external cells." Thus we have

1 Hunter (J.), Observations on Certain Parts of the Animal Economy, Edit, by
Palmer, vol. iv.

2 Waldeyer, " Bemerkungen liber den Ban der Menschen- und Affen-
placenta," Arch. f. mikr. Anat., vol. xxxv., 1890.

3 Hunter (W.), Anatomy of the Human G'ravid Uterus, Birmingham, 1777.

4 Mayow, Tractus Tertius de Respirationc Foetus in Utero, 1674.

5 Ray, The Wisdom of God in the Creation, lath Edition, 1754.
0 See Preyer's Specielle Physiologie des Embryo, 1883.

7 Goodsir, Anatomical and Pathological Observations, Edinburgh, 1845.

FCETAL NUTRITION: THE PLACENTA 395

the active part of placental metabolism referred for the first time to
the cells of the villi.

The importance of the intervillous spaces for fcetal nutrition was
first emphasised by Weber,1 and they were the subject of close
attention. The Hunterian doctrine that in the human placenta they
contained blood was not yet established, and their mode of development
gave rise to a long-continued controversy. John Hunter considered
them out with the maternal vascular system, and his view was
supported by Owen,2 Kolliker,3 and Farre.4 Weber and Reid 5 held
that the spaces were bounded by a thin maternal membrane, and
Goodsir described two layers of maternal tissue between the blood in
the sinuses and the vessels of the villi.

The investigation of the intervillous spaces and the epithelial
investment of the villi was carried on by Turner, Ercolani, Langhans,
and many others. Turner 6 and Waldeyer looked on the intervillous
spaces as dilated maternal capillaries; but while Turner held that
the villi, at least in part, penetrated their endothelium, Waldeyer
supposed that they pushed the endothelium before them, and so got
a covering of this maternal layer. Langhans 7 regarded the spaces as
formed by that part of the lumen of the uterus which lay between
the surface of the mucosa and the chorion, and thought that the villi
by eroding vessels came to be bathed in extravasations of maternal
blood. Klebs8 considered them to be lymph-spaces, and therefore
extra- vascular ; and Jassinsky 9 described them as being formed by
the penetration of the villi into the maternal glands, whose epithelium
came to clothe the villi externally. Now it has been proved from
the examination of early ova that the intervillous spaces are entirely
foetal and are formed in the epiblast.

The investigations of Langhans proved to be the turning-point
in the controversy regarding the investment of the villi. He showed
that it consisted in the earlier stages of pregnancy of a double
covering, a deep layer of cells (Langhans' layer), and superficially a
mass of " canalised fibrin." The presence of fibrin had been noted

1 See Wagner's Elements of Physiology, translated by Willis, London, 1841.

2 See note in John Hunter's Collected Works, Edit, by Palmer, vol. iv.

3 Kolliker, Entwicklungxqeschichte, 1861, 1884, etc.

4 See Tod's Cyclopaedia, Article " Uterus," 1858.

5 Reid, "On the Anatomical Relations of the Blood-Vessels of the Mother
to those of the Foetus in the Human Species," Edinburgh Medical and Surgical
Journal, vol. Iv., 1841.

6 Turner, "Some General Observations on the Placenta, etc.," Jour, of Anat*
and Phys., vol. xi., 1877.

7 Langhans, " Untersuohungen iiber die menschliche Placenta," Arch. /.
Anat. u. Phys., Anat. Abth., 1877.

8 Klebs (E.), "Zur vergleichende Anatomie der Placenta," Arch. f. rnikr*
Anat., vol. xxxvii., 1891.

9 Jassinsky, " Zur Lehre iiber die Struktur der Placenta," Virchow's A
vol. xl., 1867.

395 THE PHYSIOLOGY OF REPRODUCTION

by Weber and several of his successors ; Winkler l proved it to be
a constant phenomenon, and gave it the name " Schlussplatte " ; but
it was Langhans who first described its relations, and suggested its
probable origin from the foetal epiblast. The cellular layer, according
to Langhans, was mesoblastic. Kastschenko2 first described both
layers as epiblastic, and showed that the outer layer was a syncytium
or mass of nucleated protoplasm without cell-boundaries. Such
investigations led to the feeling that the structure of the placenta
could only be understood by tracing its development from very early
periods of gestation. Hence the search for and examination of young
human ova were stimulated, and the study of the uterine condition
in age-series of pregnant animals was begun. Up to this time the
chief controversies had raged around the human placenta. Com-
parative placentation had engaged the attention of few morphologists,
among whom Turner, the "grand-master of placental research"
(Hubrecht 3), was facile princeps. But within recent years investi-
gations have been carried out on many orders of placental Mammals.
Of these the most important are the researches of Duval and
Hubrecht, which have established that the discoid placenta is
essentially " a maternal haemorrhage encysted by foetal elements."

II. STRUCTUEE AND FUNCTIONS OF THE EPITHELIAL
INVESTMENT OF THE VILLI

The cellular layer of the villi is a temporary structure, and
disappears to a great extent comparatively early in pregnancy. It
is generally looked on as the mother zone of the outer syncytial
layer. Strahl4 states, however, that in one of the new- world apes
it is not present at a stage as early as that of Peters' human ovum,
though a thick syncytial layer is present. Processes of it precede
the mesoblastic outgrowths in the formation of the villi, and by a
special proliferation of the cells at the tips of the villi, the "Zellsaulen"
of Langhans, an attachment to the decidua is effected. While present,
the cellular layer lies in the path by which the nutriment for the
foetus is carried to the villous capillaries, but it is not known whether
it exerts any metabolic influence. Peters has suggested, without any
very definite evidence, that it may have a coagulating action on
maternal blood, necessitating the interposition of the syncytial layer.

1 Winkler (F. N.), "Zur Kenntnis der menschlichen Placenta," Arch, f,
Gyniik., vol. iv., 1872.

2 Kastschenko, " Das menschliche Chorionepithel und dessen Rolle bei der
Histogenese der Placenta," Arch. J. Anat. u. Phys., Anat. Abth., 1885.

3 Hubrecht, "The Placentation of Erinaceus europceus" Quar. Jour. Micr.
Science, vol. xxx., 1889.

4 Strahl, "Ueber Placentarsyncytien," Anat. Anz., vol. xxix., Erganzungsh.,
1906.

FCETAL NUTRITION: THE PLACENTA 397

The syncytium is more permanent. In the earliest human
ovum yet examined it already constitutes a considerable mass, and
a similar thickening over the whole or part of the circumference of
the blastocyst occurs early in all the Deciduata. Where a decidua
reflexa exists, the early proliferation appears to be related to the
excavation of the cavity in which the ovum lies. In discoid placentae
the mass is vacuolated, and maternal blood is contained in the lacunae.
In the later stages of pregnancy it forms an attenuated membrane
over the villi, and may wholly disappear at parts. The nuclei are
numerous, and most of the authorities agree on the absence of mitoses,
some holding that they divide directly, others that they have lost the

I si I'

FIG. 98. — Part of an early human chorionic villus. (From Hofbauer's
Biologic der menschlicheii Plazenta, Braumiiller.)

ft, Biirstenbesatz with basal corpuscles ; *, syncytium ; /, Langhans' layer,
one cell dividing mitotically (/').

power of division. The protoplasm has a foam-like structure, and in
man it is condensed superficially to form a layer which bears the
" Biirstenbesatz " or striated border (Fig. 98). This consists, as seen
in fixed specimens, of a series of fine stria? running perpendicularly
to the surface, and its structure and function have been much
discussed since it was first described by Minot.1 Some have denied
its existence during life, and ascribed it wholly to the method of
preparation. But Hofbauer 2 has shown that the fresher a specimen
is when obtained, the easier it is to demonstrate the stria?, by
methods of staining, and, therefore, it is probably a vital structure.
Kastschenko looked on the striae as fine hairs which projected from
the surface of the cells, and by their vibrations created a stream in
the maternal blood of the intervillous spaces. In specimens stained

1 Minot, "Uterus and Embryo," Jour, of Morphol., vol. xi., 1889.

2 Hofbauer, Biologie der inenscMichen Plazenta, Leipzig, 1905.

398 THE PHYSIOLOGY OF REPRODUCTION

with iron-hsematoxylin, knobs may be seen at the bases — basal
corpuscles or blepharoblasts — and they may constitute the motor
centre for the ciliary beats. But no movements have yet been
observed, and von Lenhossek 1 calls them " stereozilien," or stationary
cilia, suggesting that they may help to break down vessel-walls
during the burrowing of the syncytium into the serotina. Sometimes
they appear not to project free on the surface but to lie in the
superficial stratum ; then lighter and darker striae alternate, and it
is this appearance which has led to the name " striated edge."
Bonnet 2 ingeniously remarks that it proves the fretal origin of
the syncytium, because, if it were uterine, the free edge would be
formed by the bases of maternal cells, and they could not possess a
" Biirstenbesatz." The same appearance has been noted in intestinal
epithelium, but its significance is unknown. In the placenta Graf v.
Spee 3 attributes the appearance to the teasing out of the surface of
the protoplasm, and looks on it as evidence of a strong flow of fluid
through the syncytium. It has also been suggested that the thin
rods may be hollow and act as pores by which nutriment may enter
the syncytium, or by which a secretion of the syncytium may pour
out in order to prepare the constituents 'of the maternal blood for
their transference to the foetus.

It is still undecided whether the syncytium possesses amoeboid
motility. V. Lenhossek examined a human ovum several minutes
after its removal from the uterus and observed, as has already been
stated, no ciliary movements ; but he considered it not improbable
that the syncytium underwent changes of form. Hofbauer tried
unsuccessfully to demonstrate such movements in a specimen
examined immediately after its removal.

The core in young villi consists of a matrix, homogeneous or
delicately fibrillated. In it are placed the blood-vessels and con-
nective tissue corpuscles with long branching processes, which form
a network in the matrix, and probably provide a series of lymph-
channels. Kastschenko also described special cells, with large nuclei,
which he took to be wandering cells. But Lenhosse'k proved that
they existed before leucocytes or lymph-cells appeared, and must,
therefore, be formed in the villi and derived from mesoblastic cells.
Hofbauer has observed them also in the lumen of the fretal vessels,
and suggests a possible transformation to leucocytes.

Our ideas upon the function of syncytia are largely based on

1 V. Lenhoss6k, Verhandl. d. anat. Kongresses in Halle, 1902. See Centralbl.
f. Gyncik., 1904, Nr. 7.

2 Bonnet, " Uber Syncytieri, etc.," Monatsschr. f. Geburtsh. u. Gyncik., vol.
xviii., 1903.

3 Graf v. Spee, " Neue Beobachtungen iiber sehr friihe Entwickelungsstufen
des raenschlichen Eies," Arch.f. Anat. u. Phys., Anat. Abth., 1896.

FOETAL NUTRITION: THE PLACENTA 399

the investigations of His : l- " They are not really specific tissue
structures, but tissue conditions requiring definite phases of proto-
plasmic vitality. They occur along with a high degree of activity—
with increased absorption and action on material — as well as with
increased motility. Favourable conditions of nutrition form the
fundamental condition for the existence of syncytia, and such
conditions are certainly well offered in the uterus." At the present
time the syncytium is regarded as of the highest importance in
foetal nutrition. Strahl2 and Heinricius,3 noting its gradual and
progressive diminution as pregnancy advanced, supposed that it
formed a part of the nutriment for the embryo, but this idea has
not been adopted. The general theory is that it is essential in
maintaining the interchange of material between mother and fcetus.
The substances necessary for the building up of the foetal body
may be divided into two groups — diffusible and non-diffusible. The
passage of the former can be explained by physical laws, but it is
different with the non- diffusible or colloid substances. This is a
difficulty which does not belong to the placenta alone, but to every
organ of the body, and authorities are divided between two theories,
the mechanical and the vital. The supporters of the mechanical
theory hold that all the processes occurring in the placenta are
possible by the laws of filtration and osmosis, and they have carried
out numerous experiments to prove that substances in solution may
pass across the placenta in both directions. Others, paying special
attention to the nature of the barrier formed by the epithelial
covering ,of the villi, deny that by such physical processes the non-
diffusible substances with large molecules, e.g. haemoglobin and other
blood proteins, can be absorbed by the syncytiimi. They postulate
a vital action on the part of the cells, by which the necessary
material is selected by the syncytium, and altered to a form in which
it may be transmitted to the foetal circulation. It is not yet settled
whether the activity of the syncytiimi is due to a phagocytic power
or to an enzyme action.

There is a third theory regarding the transmission of nutritive
material from the mother to the foetus, viz. by the actual passage of
maternal leucocytes, charged with nutriment, from the one circulation
to the other. This theory was first advocated by Eauber4 as the

result of microscopic investigations, and he instanced, as further

\

1 His, " Die Umschliessung der menschl. Frucht wahrend der f riihesten Zeit
der Schwangerschaft," Arch.f. Anat. u. Phys., Anat. Abth., 1897.

2 Strahl, "Der Bau der Hundeplacenta," Arch. f. Anat. u. Phys., Anat. Abth.,
1890.

3 Heinricius, " Ueber die Entwicklung und Struktur der Placenta beim
Hunde," Arch.f. mikr. Anat., vol. xxxiii., 1889.

4 Kauber, Ueber den Ursprung der Milch und die Erniihrung der Frucht im
allgemeinen, Leipzig, 1879. Also Zool. Anz., No. 70.

400 THE PHYSIOLOGY OF REPRODUCTION

evidence in its favour, the greater number of leucocytes in the blood
of the umbilical vein than in that of the artery. This view, which
explained satisfactorily the passage of non-diffusible materials,
subsequently received wide support. Thus Wiener l said : " It may
be held as nearly without doubt that leucocytes cross from the
maternal to the foetal blood," and Preyer 2 considered the passage of
leucocytes " indisputable." The first objection was raised in a paper
by Paterson.3 In it he recorded three cases of pregnancy complicated
by leucocythsemia in the mother, and stated that the infants appeared
quite normal and healthy, and their blood was of the usual colour
and not white like the mothers'. These results were corroborated
in similar cases by Cameron 4 and Sanger,5 who actually counted the
fetal leucocytes and found no increase. More recently, Spire and
Perrin,6 in a case where the mother had pernicious anremia, found
that the foetal blood was practically normal. These observations,
and the inability of other investigators to demonstrate healthy
leucocytes in the tissues intervening between the maternal and foetal
blood, have led to the abandonment of Rauber's theory.

But though maternal leucocytes do not pass as such straight
into the foatal blood, they may be important in another way. In
Ruminants, Bonnet7 has drawn attention to the enormous number
of degenerated leucocytes in the uterine milk, and demonstrated
their absorption by the ectoderm, and similar observations have been
recorded in Carnivores. In these orders leucocytes undoubtedly
form a part of the embryonic nutriment. In the rest of the
deciduate Mammals they seem to play a less important part.

III. THE DECIDUA

In the uterine mucosa during pregnancy the most noticeable
change occurs in the interglandular tissue of discoid placentae, in
which decAdual cells are formed. Various opinions have been held
regarding their origin. Langhans, Hennig>8 and others held that
they were enlarged and modified leucocytes, but they could not

1 Wiener, " Die Ernahrung des Fotus," Samml. Klin. Vortriige, No. 290.

2 Preyer, Specielle Physiologic des Embryo, 1883.

3 Paterson, " Cases of Acute Leucocythsemia in connection with Pregnancy,"
Edinburgh Med. Jour., 1870.

4 Cameron, " The Influence of Leucaemia upon Pregnancy," Internat. Jour, of
the Med. So., 1888.

5 Sanger, " Ueber Leukamie bei Schwangeren und angeborene Leukamie,"
Arch. f. Gyniik., vol. xxxiii., 1888.

6 Spire and Perrin, " Un Cas d'Anernie pernicieuse de la Grossesse," Bull, de
la Soc. d?0bstet. et de Gyn. de Paris, (Nov.) 1912.

7 Bonnet, "Uber Embryotrophe," Deuts. med. Wock., 1899.

8 Hennig, Studien liber den Ban der menschlichen Placenta, etc., Leipzig,
1872.

FGETAL NUTRITION: THE PLACENTA 401

support their theory by direct observation. Overlach l and Frommel 2
described them as modified glandular cells, but there is no doubt
that the true origin is, as Creighton3 first suggested, from the
interglandular tissue of the mucosa. This consists of connective
tissue of an embryonic type, which allows of a rapid transformation
of its cellular elements. Masquelin and Swaen4 demonstrated this
mode of origin in Rodents, and were supported by Minot, and Hart
and Gulland.5 Leopold's studies of early ova showed that the same
origin was most probable in man, and Peters described in the mucosa
next the ovum connective tissue cells undergoing a decidual trans-
formation.6 Their first appearance in the superficial layers of the
mucosa has suggested a stimulus for their formation arising from
the product of conception." The study of early human specimens
has effectually disproved Ercolani's8 idea that the uterine mucosa
was first entirely destroyed by the developing ovum, and then
replaced by decidual tissue formed from the cells of the vessel-walls.
Such an endothelial proliferation does, however, occur in certain
animals, e.g. hedgehog (Hubrecht 9) and bat (Nolf 10), and probably in
ectopic gestation in man.

The rapid increase in the size and number of the decidual cells,
together with the dilatation of the blood-vessels, leads to a great
increase in the thickness of the serotina. At a certain stage it
reaches its full development, and then gradually diminishes till, at
the end of gestation, it forms only a thin layer, and even disappears
entirely at parts so that the villi impinge on the muscular wall.

Individual decidual cells have probably a short life-history.
Even at a comparatively early period many of them are found in

1 Overlach, " Die pseudomenstruirende Mucosa Uteri nach akuter Phosphor-
vergiftung," Arch. f. mikr. Anat., vol. xxxv., 1885.

2 Frommel, " Beitrag zur Frage der Wachstumsrichtung der Placenta," Zeitsch.
f. (Jeburtsh. u. (tynak., vol. xxxvi.

3 Creighton, " The Formation of the Placenta in the Guinea-pig," Jour, of
Anat. and Phys., vol. xii., 1878.

4 MasquelLn and Swaen, " Premieres phases du developpement du placenta
chez le lapin," Bull, de VAcad. roy. de Belg., 1879.

6 Hart and Gulland, "On the Structure of the Human Placenta, etc. "'Labor.
Rep., Roy. Coll. Phys., Edinburgh, vol. iv., 1892.

6 Cf. Ulesko-Stroganoff, " Zur Frage von deni feinsten Bau des Decidua-
gewebes, etc.," Arch. f. Gynak., vol. Ixxxvi., 1908.

7 Under abnormal conditions the formation of decidual cells occurs even
although no ovum is present in the uterus, e.g. in tubal pregnancy in the
human female. This indicates a chemical stimulus, probably from the corpus
luteum, effected through the blood-stream (see p. 368). Moreover-, it is known
that decidual tissue is formed as a result of artificial or mechanical stimuli,
provided that an active corpus luteum is present in the ovary (see p. 374).

8 Ercolani, " Sulla unita del tipo anatomico della placenta," Mem. delV Accad.
di Bologna, 1876.

9 Hubrecht, " The Placentation of Erinaceus europ&us," Quar. Jour. Micr.
Science, vol. xxx., 1889.

10 Nolf, "Modifications de la muqueuse uterine pendant la gestation chez le
murin," Arch, de Biol., vol. xiv., 1896.

402 THE PHYSIOLOGY OF REPRODUCTION

various stages of hyaline degeneration, giving rise in part to the
layers of fibrin, and as pregnancy advances there is a gradual
extension of the fibrinous change. The degeneration of the decidual
tissue would seem to be due to the influence of the foetal epiblast, as
in man it occurs much earlier and more abundantly in the serotina
and reflexa than in the vera (Webster1). Its gradual diminution
during pregnancy indicates an absorption of the decidua. That
maternal tissues do not play a large part in this absorption is
probable from the small number of leucocytes and the absence
of lymph-channels in the neighbourhood of the nbrinous masses.
At the same time, specialised decidual cells, which have the
power of destroying the rest of the decidual tissue, have been
described in the hedgehog,2 rat, and other animals. But it is now
generally accepted that the fo3tal ectoderm from the earliest
stages of pregnancy is able to disintegrate the cells with which it
comes in contact, and to absorb the degenerate products. To that
part of the foetal epiblast which is thus adapted for the acquirement
of embryonic nutriment the name of trophoblast has been given by
Hubrecht. It forms the outer or ectodermal layer of the false
amnion or chorion (see below, p. 412).

Along with the gradual absorption of the degenerated parts of
the decidua, and the great increase in the extent of the serotinal
surface as pregnancy advances, there is probably a continued
formation of new decidual elements. Pfannenstiel attributes the
new formation to the perivascular tissue, and Webster to groups of
active cells, the " Ersatz-zellen " of Klein,3 found here and there in
the inucosa. Whatever their origin is, we may see, even in the shed
placenta at full time, well-formed and apparently healthy decidual
elements as well as the fibrinous masses containing cellular
fragments.

Within recent years there has been a tendency to belittle the
importance of the connective tissue elements of the placenta. This
has been largely due to the wider acceptance of the foetal origin of
the syncytium, and to the conception of the placenta as a maternal
haemorrhage circumscribed by foetal structures. But the same idea
has been encouraged by some who look on the syncytium as maternal,
and they adduce as evidence the obvious degeneration in the decidua
during the greater part of pregnancy. Pfannenstiel maintains that
decidual cells are, from the beginning, degeneration forms of the

1 Webster, Human Placentation, Chicago, 1901.

2 In a later memoir Hubrecht assigns to these cells, the deciduofracts of the
hedgehog, an origin from the outer layer of the trophoblast. See footnote,
p. 496.

3 Klein, "Entwicklung und Euckbildung d. Decidua," Zeitich. f. GebnrtsL ".
Gynak., vol. xxii.

FCETAL NUTRITION: THE PLACENTA 403

connective tissue cells and are of use only as pabulum to be
absorbed by the ovum. But during the whole of pregnancy, as
mentioned above, there exist in the placenta decidual cells which,
in their appearance and staining properties, show no resemblance to
degenerated cells. From their abundance and great specialisation
they have in all likelihood definite functions to perform. Their first
formation dates from the destruction of the surface epithelium when
the blastocyst comes in contact with the connective tissue, and the
earliest to appear are in the neighbourhood of the ovum. Their
position and general appearance in different orders suggested to
Turner a maternal reaction against the advance of the parasitic ovum,
and the same idea has been forced on different observers. Fothergill l
speaks of the decidua preventing the injurious invasion of the uterine
wall by the foetal elements. Chiprnan's 2 figures of the placenta of
the rabbit show that the ectoplacenta advances more rapidly where
it encounters a vessel than where it lies against decidual cells. Wade
and Watson3 have noted its resemblance to young granulation
tissue in the mucosa of the Fallopian tube in an early ectopic
pregnancy. Bryce and Teacher,4 in their description of the youngest
human ovum yet examined, say : " The decidua formation is a process
of a conservative nature, by which, during the early months of
pregnancy, the activities of the trophoblast are limited and controlled
until such time as placentation is complete." Whether or not the
decidua forms the protection to the mother, there is increasing
evidence that the trophoblast does not invade the decidua to the
extent supposed by the older authorities. This was first emphasised
by Hubrecht in the hedgehog, and has more recently been advocated
by Webster, and by Bryce and Teacher, in man.

Hoffmann5 and Ahlfeld6 considered the decidua to be of the
nature of a diffuse gland whose cells secreted a nutritive juice for
the wants of the foetus. They stated that they could demonstrate
such a secretion in the " intervillous " spaces formed by the separation
of the decidual cells ; but their observations have been discounted by
the investigations of Werth,7 who showed that the spherical globules
described by Hoffmann were never present in the fresh placenta, but

1 Fothergill, "Decidual Cells," Edin. Med. Jour., vol. v., 1899.

2 Chipman, " Observations on the Placenta of the Rabbit, etc.," Edin. Roy.
Coll. Phys. Labor. Rep., vol. viii., 1903.

3 Wade and Watson (B. P.), "The Anatomy and Histology of an Early Tubal
Gestation," Jour, of Obstet. and Gynec. of the Brit. Emp., 1908.

4 Bryce and Teacher, Contributions to the Study of the Early Development and
Imbedding of the Human Ovum, Glasgow, 1908.

6 Hoffmann, " Sicherer Nachweis der sogennanten Uterinmilch beim Men-
schen," Zeitsch. f. Geburtsh. u. Gyniik., vol. viii., 1882.

6 Ahlfeld, Berichte «. Arbeiten aus der gebiirtsh. Klinik zu Giessen, Leipzig,
1883.

7 Werth, " Beitrage zur Anatomic, Physiologic, und Pathologic der mensch-
lichen Schwangerschaft," Arch. f. Gyniik., vol. xxii.

404 THE PHYSIOLOGY OF REPRODUCTION

appeared only after its separation, and probably consisted of droplets
exuded by the dying chorionic epithelium. It may be mentioned
here that the " boules," described by Nattan-Larrier x as an internal
secretion of the syncytium, have been thought by many to be a
post-mortem appearance.

In Rodents the decidual cells have an important and definite part
to play in synthesising and storing glycogen as a supply of carbo-
hydrate for the foetus. In man also the decidual cells contain
glycogen at an early period. Pat globules infiltrate the decidual cells
of various animals at a stage when there is no question of a fatty
degeneration taking place in the cells. Finally, the cells appear to
have the power of ingesting and decomposing erythrocytes, but their
relations to the iron-metabolism of the foetus require further study.

PART II

THE FIRST STAGES OF PREGNANCY: PLACENTAL
CLASSIFICATION

I. THE OVARIAN OVUM

WHILE still in the ovary, the ovum obtains the necessary nutriment
by means not yet discovered. In the Graafian follicle it is surrounded
by the zona pellucida and externally the corona radiata.2 The origin
of the zona pellucida has been variously described. According to
some authorities it is the thickened outer edge of the ovum itself,
a true vitelline membrane, but it is more probably a deposit from the
cells of the corona radiata. Its structure is almost homogeneous,
but with the highest powers of the microscope fine stripe are seen
running from without inwards. Their appearance indicates the
possibility that they are pores or delicate canals by which protoplasmic
processes of the cells of the corona radiata, or a secretion of these cells,
may reach the ovum and nourish it (see p. 121). Whatever the
source of the food-supply of the ovum is, it not only increases in size
until it is ripe for deliverance, but stores in its protoplasm yolk
granules, the deutoplasm of Beneden, which increase in number as the
ovum approaches maturity. The granules vary in size and number
in different species, and also in their position. They may be mingled
uniformly through the cytoplasm, or be collected at the marginal
zone (sheep), or at the periphery of thfe central zone (man). During
the earliest stages of segmentation, when perhaps food is not readily

1 Nattan-Larrier, " Fonction secretaire du placenta," Comp. Rend, de VAcad.
de Sc., vol. lii., 1900.

2 Or zona radiata, i.e. the innermost layer of follicular epithelium and within
the discus proligerus.

FCETAL NUTRITION: THE PLACENTA

405

accessible, or a specialised form of nutriment is required, the granules
are used up.

II. THE FERTILISED OVUM AND ITS COVERINGS

When the ovum leaves the ovary it carries with it the zona
pellucida and cells of the corona radiata. After fertilisation, which
most probably occurs in all animals at the outer end of the oviduct
or Fallopian tube, the cells disappear and are replaced in some species
by a homogeneous sticky layer of albuminous material. According

FIG. 99. — Early blastocyst of the rabbit. (From Hertwig's Entioicklnngs-
geschichte das Menschen und der \Yirbelthiere. By permission of Gustav
Fischer.)

a, Albumen layer ; zp, zona pellucida ; £, trophoblast ; AT, segmentation
cavity ; ec, mass of embryo cells.

to Robinson,1 it is derived in part from the disintegrated cells of the
corona radiata, but most of it seems to be obtained from the secretion
of the tubal and later of the uterine glands.2 It is covered by villous
tufts, which led to its designation as prochoriom by Henson. But the
tufts are merely casts of the gland-ducts, due to the coagulation of
the secretion by the use of reagents.

The investment formed by the two layers around the ovum is
very thick in Marsupials. In Ungulates it forms a thin coat, which

1 Robinson, " On the Early Stages of Development of Mammalian Ova, and
on the Formation of the Placenta," Hunterian Lectures, Jour, of Anat. and
Phys., vol. xxxviii., 1904.

2 Bonnet, " Ueber das Prochorion der Hundekeimblase," Anat. Am., vol. xiii.,
1897.

406 THE PHYSIOLOGY OF REPRODUCTION

disappears at a comparatively early stage in the pig, sheep, and deer.
In the last named, according to Bischoff, there is no albumen layer.
In Carnivores there is invariably a firm coat of zona pellucida or
albumen layer, or both, which persists, in the dog and ferret at least,
till the appearance of the primitive streak and the commencement of
the formation of the mesoderm (Robinson). In Rodents there are
differences. In the rabbit (Fig. 99) the albuminous layer is well
marked while the fertilised ovum is still in the Fallopian tube ; on
the fourth day, when the uterus is reached, it rapidly thins but
remains up to the eighth day (Assheton1). In the rat the covering
disappears early — usually about the eight-cell stage. In the mole
the covering is thick, and, according to Heape,2 the albumen layer
is applied in the uterus and not in the Fallopian tube. It persists, as
in the shrew, till the embryonic ectoderm appears on the surface
of the ovum. In the hedgehog and bat it disappears before the
blastocyst is formed, and in 1'upaia javanica it may be already absent
in the two-cell stage. Little is known of it in the Primates ; in the
earliest ovum investigated, the four-cell stage of Macacus nemestrinus,
it had already disappeared.

With regard to its functions, there is little doubt that the
degenerating cells of the corona radiata, and later the albumen layer,
serve as food for the growing mass of the ovum in the Fallopian tube
and uterus. In the investment in the mouse, Jenkinson3 found
nutritive substances — fat, and probably also protein matter. In
addition, Bomiet has adduced strong evidence to show that it is
absorbed by the ectoderm of the blastodermic vesicle. In the rabbit
the albumen layer forms a tough, strong membrane enclosing at the
end of the third day the solid morula. Within the mass of cells a
cavity develops and rapidly increases by diffusion inwards of fluid.
" It is hardly conceivable that the delicate cells could cause expansion
of the tough albuminous wall. Rather the osmotic current is more
inwards than outwards, either simple or more probably assisted by
the vital activity of the cells" (Assheton). Heape had previously
pointed out that the increasing fluid must be secreted into the interior
of the blastocyst under considerable pressure, as the vesicle remains
spherical and extends the uterine walls before it. Once inside, the
fluid exerts a greater or less hydrostatic pressure, which is counteracted
by the albumen layer, and the rupture of the vesicle is prevented.
At the beginning of the cavity-formation in the morula, the cells are

1 Assheton, " The Attachment of the Mammalian Embryo to the Walls of the
Uterus," Quar. Jour. Micr. Science, vol. xxxvii., 1895.

2 Heape, "The Development of the Mole (Talpa europcea), etc.," Quar. Jour.
Micr. Science, vol. xxiii., 1883.

3 Jenkinson, " Observations on the Physiology and Histology of the Placenta
of the Mouse," Tijd. Nederl. Dicrk., Ver. ii., Dl. 7.

FCETAL NUTRITION: THE PLACENTA 407

not yet pressed on by the investment. Later the vesicle increases in
size, and the outer cells are pressed and flattened. At the same time
the albumen layer is thinned, and is soon hardly perceptible. Finally
it ruptures, and immediately afterwards the blastodermic vesicle is
flaccid, apparently from injury to its wall.

Besides its nutritive and protective function, the investing layer
may prevent the contact of the external cells of the blastodermic
vesicle with the cells of the uterus. Only when it has disappeared
is fusion of the maternal and foetal elements possible. Robinson has
followed out this idea in different Mammals. He suggests that in
those animals (Carnivores, rabbit) in which the embryonic ectoderm
reaches the surface, the albumen layer prevents contact with the
uterine wall till differentiation of the ectodermal cells has taken
place to such an extent that they are no longer disposed to fuse with
the uterine tissues. In those in which the embryonic ectoderm never
reaches the surface (mouse, guinea-pig, hedgehog, bat, probably
Primates), the investment disappears before the blastula is attained.

With the disappearance of the zona, the developing ovum lies
naked in the Fallopian tube or the uterus. It takes some time to
complete the journey along the tube — about eighty hours in the
rabbit, and a little longer in the sheep ; in the guinea-pig it is said
to reach the uterus on the seventh day after copulation and while in
the morula stage.1 For a further period it remains unattached in the
uterine cavity, and then, by processes which vary in different orders,
it obtains attachment — loose in Marsupials and firmer in the other
orders. Peters2 has described a human ovum of five or six days
when the decidua was still undergoing differentiation. The ovum
was sunk in it but was not as yet completely covered. Leopold 3 in
a uterus removed surgically for cervical cancer found a seven days'
ovum entirely enclosed by the decidua.

At first each blastomere is nourished separately ; but when the
blastocyst is formed, the greater part of its outer layer is set aside to
look after the nutrition of the whole, and takes no share in the
formation of the embryo or amnion. To that part Hubrecht gave
the name of trophoblast,* and the term has been generally accepted.
Already, before the embryo is elaborated, provision is in this way
made for its maintenance.

III. THE UTERINE MUCOSA
While the ovum is still in the oviduct, no obvious changes occur

1 Von Spee, " Die Implantation des Meerschweincheneies in die Uterus-
wand," Zeitsch. f. Morph. vnd AnthropoL, vol. iii., 1901.

2 Peters, fiber die Einhettung des Menschlich.cn Eies, Leipzig und Wien, 1899.

3 Leopold, Uterus und Kind, Leipzig, 1897.

4 See below, p. 412.

408 THE PHYSIOLOGY OF REPRODUCTION

in the uterus itself. In the sheep, Asshetori,1 detected no difference
except an increase in the number of the leucocytes. There was no
sign of activity in the uterine glands or blood-vessels. When the
ovum reaches the uterus changes begin — dilatation of blood-vessels
and lymphatics, widening and increased tortuosity of glands,
disappearance of cilia from the surface epithelium. The whole
mucosa is soft and oedematous, and there may even be a transudation
of lymph entering the uterine cavity and mingling with the glandular
secretion to form a supply of nutriment for the ovum before attach-
ment. Great differences, however, occur, and it is more convenient
to describe the changes in the uterine mucosa in each order.

IV. PLACENTAL CLASSIFICATION

At the outset we are beset with the difficulty of grouping
Mammals in such a way as to show how the variations in the
anatomy and physiology of the placenta have been evolved. Well-
marked differences, such as occur in other organs and serve to
differentiate Mammals into certain orders, are not always to be
observed in their placenta. In widely diverging groups there may
be striking similarities in placentation, while great differences may
exist in closely related types. On this account the most satisfactory,
and indeed the only possible, classification of Mammals for our
purpose is one based on their placental characters. Such a classifica-
tion was introduced by Huxley2 in 1864. He divided Mammals into
two great sections according as their placentae were non-decidnate or
deciduate? In Deciduates the substance of the mucosa undergoes
rapid growth and textural modification to form decidual tissue, and
the maternal and foetal parts of the placenta become firmly united.
In Non-deciduates there is no formation of decidual tissue, and at
parturition the foetal villi are simply drawn out like the fingers from
a glove, no vascular substance from the mother being thrown off.

In a later publication 4 Huxley attempted to arrange all Mammals
in one or other division. The Deciduata are classed in two groups
according to the external appearance of the placenta, which is either
zonary? as in Carnivora and Proboscidea ; or discoid, as in Rodentia,
Insectivora, Cheiroptera, Lemuridae, Simiidse, and Primates. The
Non-deciduata are the Ungulata and Cetacea. The Sirenia and

1 Assheton, " The Morphology of the Ungulate Placenta, etc.," Phil. Trans.
Roy. Soc., London, Ser. B., vol. cxcviii., 1906.

2 Huxley, The Elements of Comparative Anatomy, London.

3 Thirty years earlier Weber had suggested a similar division into caducous
and non-caducous ; but his terms, although accepted by von Baer and Eschricht,
were displaced by those of Huxley.

4 Huxley, Introduction to the Classification oj Jiammals, London, 1869.

6 When the chorionic villi are limited to an annular area the placenta is
called zonary.

FCETAL NUTRITION: THE PLACENTA 409

Edentata offer difficulties. Of the latter, Manis has a diffuse
placenta, Bradypus a poly-cotyledonary, and Orycteropus a zonary and
deciduate placenta. One of the Sirenia, the dugong, which possesses
a zonaiy but not deciduate placenta, illustrates a type not repre-
sented at all in Huxley's classification. No maternal tissue is lost at
birth; but, in addition, part of the foetal tissue remains attached to
the uterus and is absorbed (Turner1). The placenta of the mole
is not shed at birth, but becomes gradually absorbed by the mother.
For such Hubrecht 2 suggested the term contra-deciduate.

The classification of Strahl3 does not promise to be any more
satisfactory. He divides Mammals into two groups, one having a
" Halbplacenta " and the other a " Vollplacenta." In the former no
maternal vessels are opened and the connection is less intimate, while
in the latter haemorrhages occur during pregnancy. But in a
physiological sense the half placenta is certainly as efficient an
organ of nutrition as the whole placenta.

In view of the more recent work on the placenta, it is obvious
that Huxley's classification fails in taking no account of the
trophoblast, the most active constituent of the placenta, and in laying
too much stress on the differences at birth, i.e. on the shedding of an
organ which is of no more use, and may be considered as physio-
logically dead. Moreover, it would appear that in many of the
deciduate Mammals almost no maternal tissue except blood is lost at
birth, and maternal blood is also lost in the non-deciduate sheep. A
perfect classification must take account of the structure and behaviour
of the trophoblast during the whole course, or at least the earlier
part, of pregnancy. Without it a clear insight into the processes
which regulate foetal nutrition cannot be obtained. Eobinson 4 and
Assheton 5 have made efforts in this direction, the former emphasising
the methods of attachment of the trophoblast to the uterus, and the
latter the anatomical condition of the trophoblast at the time of its
first attachment. Hubrecht, on the basis of Huxley's statement that
Insectivora are among the most archaic of Mammals, has investigated
several members of this order as showing probably the most ancient
type of placenta, and thus affording a starting-point for a classifica-
tion. According to Huxley, the least differentiated types, the
hedgehogs and Gymimm, occupy a central position, while shrews
show resemblances to Rodents, and Tnpaicu to lemurs ; moles and
GcUeopitheci vary in other directions, while the whole order shows

1 Turner, "On the Placentation of Halicore dugong" Trans. Roy. Soc. Edin.,
vol. xxxv., 1889.

2 Hubrecht, " Spolia Nemoris," (fitar. Jour. Micr. Science, vol. xxxvi., 1894.

3 See Hertvvig, Entwicldungsgeschichte des Men»ch«n undder Wirbelthicre, 1900.

4 Robinson, Hunterian Lectures, loc. cit.

* Assheton, " The Morphology of the Ungulate Placenta," Phil. Trans. Roy.
•S'or., London, Ser. B., vol. cxcviii., 1906.

410 THE PHYSIOLOGY OF REPRODUCTION

more general relationships to Carnivores and Ungulates. But at
present these relationships are not understood. It seems impossible
to trace any connection between the placenta of the sheep, in which
there is no circulation of maternal blood in the foetal parts of the
placenta but the fcetus is nourished by uterine milk, and that of the
hedgehog, in which maternal blood circulates in the trophoblastic
lacuna? and forms the main source of nutriment.

Hubrecht3 has contributed an important memoir setting out in
some detail his views on the phylogeny of the placenta and its
classificatory value, and Assheton 2 has expressed himself as in
agreement with the general trend of Hubrecht's ideas. According
to these authorities we have on the one hand in the Ungulata,
Sirenia, Cetacea, and some Edentata a great lateral expansion of
the trophoblast, leading to the "plicate" type of placenta, and on
the other hand in Insectivora, Cheiroptera, and Primates cell
proliferation of the trophoblast producing thickenings thereof and
leading to the "cumulate" type of placenta. The differences between
the two types are summarised by Assheton as follows : —

CUMULATE PLACENTA. PLICATE PLACENTA.

Great radial proliferation of tropho- Great tangential proliferation of

blast, leading to thickening of the trophoblast, leading to folding of

membrane. the membrane.

Greater destruction of maternal tissue. Lesser destruction of maternal tissue.

Much bleeding of mother. Little bleeding of mother.

Lacunisation of trophoblast. No lacunisation of trophoblast.

Secretion of uterine glands of less use, Secretion of uterine glands of prime

or in some cases of no use, to the importance.

foetus.

Degeneration of uterine epithelium Little or no degeneration of uterine

and glands severe. epithelium and glands.

Embryo or embryos seldom fill the Embryo or embryos usually fill the

whole cavity of the uterus. whole cavity of the uterus.

According to Assheton the reason for the causatjpn of the latter
character is that " fixation is brought about or other intimate
connection in the cumulate type, while fixation in the plicate type
depends more upon the internal hydrostatic pressure of the blastocyst
upagainst the uterus — much as a pneumatic tyre retains its position
in the iron rim of a bicycle wheel."

The Carnivora are regarded as a central group with respect to
plaeentation from which either cumulate or plicate type could be
evolved. In this connection it may be recalled that in the (jestrous
cycle of the dog there is a normal pseudo-pregnant period in the
absence of gestation, and that this is to be regarded as a primitive
characteristic.

1 Hubrecht, " Early Ontogenetic Phenomena in Mammals," Quar. Jour. Nicr.
Science, vol. liii., 1908.

2 Assheton, " Professor Hubrecht's Paper, etc.," Quar. Jour. Micr. Science,
vol. liv., 1909.

FCETAL NUTRITION: THE PLACENTA 411

Hubrecht considers the extreme cumulate placenta to be more
primitive than the extreme plicate one, but his view is based on
the assumption of a non-Sauropsidan origin of Mammals with which
Assheton is unable to agree. The Lemurs are described by Assheton
as " pseudo-plicate," having been derived separately from Mammals
with a cumulate placenta. The Marsupials are regarded as being
specialised descendants of placental Mammals (Hubrecht).1

In this chapter we must be content with a review of the processes
occurring in several Mammals which have been more particularly
investigated, without straining to find how such processes have
arisen in the course of placental evolution. The arrangement of
the mammalian orders is more in accordance with the older views
of placental classification, but nevertheless an attempt has been made
to emphasise the trophoblastic characteristics.

PART III

THE FGETAL MEMBRANES, THE YOLK-SAC,
AND THE PLACENTA

I. GENERAL ANATOMY OF THE FCETAL MEMBRANES

So far no reference has been made to the part played by the
mesoblast in the nutrition of the embryo. The placenta has been
described as an organ consisting of maternal and foetal elements —
of modified uterine mucosa, and trophoblast which absorbs nutritive
material from the mucosa and from the maternal blood. The
nutriment serves in part for the nutrition of the trophoblast itself,
and in part for the growth and development of the embryo. In
the earliest stages there are as yet no embryonic vessels, and the
nutriment is transmitted from cell to cell. But as the embryo
increases in size and its requirements grow in proportion, such a
path becomes inadequate, and a vascular channel is developed in
connection with the two foetal membranes — the yolk-sac or umbilical
vesicle, and the allantois.

The mammalian yolk-sac has only a secondary importance for the
nutrition of the embryo. The blastodermic vesicle at an early stage
of development is divided into an embryonic and a non-embryonic
area. The latter is the yolk-sac which gradually becomes folded off
from the embryo. Its relations are the same as those of the yolk-sac
in Sauropsida, but the contents are an albuminous fluid instead of
yolk. It is commonly believed that the placental Mammals are

1 See also Hubrecht, '; Is the Trophoblast of Hypoblastic Origin, as Assheton
will have it ? " and " The Foetal Membranes of the Vertebrates," Quar. Jour.
Micr. Science, vol. lv., 1910.

412 THE PHYSIOLOGY OF REPRODUCTION

descended from ancestors in which the ovum had a large supply of
yolk, but that, when the fertilised ovum found a new supply of food
in the uterus, the yolk was reduced and ultimately disappeared. At
the same time the envelopes, which were developed under the
influence of the vitelline contents, have been preserved and modified
in different ways to aid uterine nutrition.1

In the early stages the development proceeds, as in birds and
reptiles, with the gradual extension of the hypoblast round the wall
of the blastocyst, which thus becomes didermic. The mesoblast grows
out between the epiblast and hypoblast, starting at the embryonic
area and gradually extending for a variable distance round the wall
of the blastocyst. Near the embryo appears the area vasculosa,
in which blood-vessels and blood are developed from the cells of
the mesoblast, while at the same time the embryo begins to be
folded off from the yolk-sac by anterior and posterior folds. The
area gradually extends further and further round. Its outer boundary
is marked by the sinus terminalis which communicates with the
vitelline veins. The blood is brought from the dorsal aortse by a
series of lateral vitelline branches. These arteries break up into a
deeper arterial network, from which the blood is collected into the
sinus terminalis and the superficial venous network, and in this way
reaches the vitelline veins and so passes to the heart.

During the spread of the mesoblast, it splits into an external
layer or somatopleur, and an internal layer or splanchnopleur. The
former is non-vascular and adheres to the inner aspect of the
trophoblast which is ectodermal, forming with it the diplo-trophoblast,
otherwise called the false amnion or chorion, and the splanchnopleur
is applied externally to the hypoblastic wall of the yolk-sac. By the
splitting a space is formed between the two layers. This is the extra-
embryonic ccelom, which thus intervenes over a larger or smaller area
between the diplo-trophoblast and the yolk-sac.

The amnion in the rabbit arises by the formation of folds of
extra-embryonic ectoderm, together with the somatopleur which is
in conjunction with it, the yolk-sac and the splanchnopleur taking
no part in the process.2 The extra-embryonic coelom is continued
into the folds, each of which contains two layers. The folds grow-
up over the dorsal surface of the embryo and eventually meet and
fuse, and when the union is complete the outer and inner layers

1 According to Hubrecht's views, the mammalian ovum is not descended from
the ovum of Sauropsida.

2 In the guinea-pig and many other species of Mammals, including probably
man, the amniotic cavity develops as a closed sac from its inception. It is
formed inside the embryonic knot, which comprises the material for both
amnion and embryo. For an account of the various ways in which the foetal
membranes are formed in the different animals see Jenkinson, Vertebrate Em-
bryology, Oxford, 1913 (see below, footnote, p. 490).

a.tr.

FIG. 100. — Formation of the amnion in the rabbit. (After van Beneden, from
Jenkinson's Vertebrate Embryology, Oxford, at the Clarendon Press.)

h.am, Head amnion fold ; (.am, tail amnion fold ; c, embryo ; all, allantois ; a.tr,
allantoidean trophoblast ; i/.s, yolk-sac ; o.tr, omphaloidean trophoblast ;
c, extra-embryonic coelom ; s.t, sinus terminalis of area vasculosa.

FIG. 101. — Foetal membranes of horse, later stage. (After Bonnet, from
Jenkinson's Vertebrate Embryology, Oxford, at the Clarendon Press.)

<•, Villus ; ep.th, epithelial thickenings of amnion ; h, hippomanes ; am.c,
amniotic cavity ; all, allantois ; y.s, yolk-sac.

4H THE PHYSIOLOGY OF REPRODUCTION

(each of which is composed of ectoderm and somatopleur) are
separated by the coelorn. The outer layer becomes the false amnioii
or chorion,1 and the inner layer the true amnion. Within the latter
and immediately surrounding the embryo is the liquor amnii. This
fluid protects the embryo from injuries and changes of temperature
besides affording freedom of movement ; moreover, it acts as a
dilating wedge during parturition. It supplies water to the embryo
but not nourishment.2

While the changes above described are taking place, the allantois
grows out (on the tenth day in the rabbit) from the hind- gut as a
vesicle lined by hypoblast, and covered externally by a layer of
splanchiiopleur.3 In some Mammals the cavity of the allantois is not
continued beyond the body-wall of the embryo, the extra- embryonic
portion consisting of a solid rod of inesoblast. In all orders below
the Primates, however, it projects free for a time into the coalom, and
later fuses, except in the Marsupials, with the whole or part of the
outer wall of the blastocyst. In the allantoic mesoblast many vessels
are developed, and branches extend into the projections which form
the cores of the villi. The blood is brought by two allantoic arteries
continued from the terminal bifurcation of the dorsal aorta, and
returned by one, or more rarely two, allantoic veins. " While the
placenta is being developed, the folding off of the embryo from the
yolk-sac becomes more complete, and the yolk-sac remains connected
with the ileal region of the intestine by a narrow stalk, the vitelline

1 See p. 476, footnote 3, and p. 490.

2 That the liquor amnii supplies water to the fcetus, according to Feldman,
is shown by the fact that hair, epidermal scales, etc., have been found amid the
intestinal contents of the newly born. On the other hand, a well-nourished
foetus may be found with almost complete absence of liquor amnii or with the
oesophageal lumen occluded, and so preventing it from swallowing the fluid.
The liquor amnii is slightly alkaline in reaction; it consists chiefly of water,
b.ut contains slight quantities of albumen, fats, and inorganic substances.
Urea and creatinin have been found in it, indicating that it may receive pro-
ducts of excretion by the foetal kidney ; moreover, benzoic acid administered to
a pregnant animal led to the appearance of hippuric acid in the liquor amnii.
As evidence that the fluid is partly of maternal origin are the facts that
potassium iodide, etc., given to the mother appears in the liquor amnii but not
in the fetal urine, and that sugar is present in the fluid if the mother has
diabetes (see below, p. 463). Jenkinson, however ( Vertebrate Embryology, Oxford,
1913), describes glucose as present normally in the liquor amnii of the cow, and
says that it increases towards the end of pregnancy, while glycogen, stored up
in the stratified epithelium on the inner surface of the' amnion, at the .same time
diminishes. For further evidence see Feldman, Principles of Ante-Natal and
Post- Natal Child Physiology, London, 1920.

3 Morphologically, therefore, the allantois is an extra-embryonic bladder.
The fluid has been found to contain glucose ('3 per cent.), albumen, mucin,
magnesium, sodium and calcium phosphates, sodium chloride, sodium sulphate,
and crystals of calcium oxalate, besides a yellow pigment, and allantoin, a sub-
stance chemically related to uric acid. It seems, therefore, that the allantois,
besides its more important function in connection with the formation of the
placenta, acts as a receptacle for foetal excretory products. See Jenkinson, loc. cit.

FCETAL NUTRITION: THE PLACENTA 415

duct. While the true splanchnic stalk of the yolk-sac is becoming
narrow, a somatic stalk connecting the amnioii with the walls of the
embryo is also formed, and closely envelops the stalk both of the
allantois and yolk-sac. The somatic stalk, together with its contents,
is known as the umbilical cord " (Balfour x). The yolk-sac atrophies
completely in some, but in others it is only removed at birth.

II. THE NUTRITIVE IMPORTANCE OF THE YOLK-SAC

When the blastodermic vesicle becomes adherent to, or sinks into,
the uterine mucosa, the wall of the yolk-sac in some orders becomes
intimately related to the uterine mucosa and is nourished by it.
Even in the non-mammalian Vertebrata the latter condition has been
observed. In the Lacertilia the yolk-sac absorbs nutriment from the
uterus through the porous shell. In Mustelits Icevis the embryos lie
in a fluid derived from the surface secretion and a lymphoid transudate
of the uterine mucosa. It passes through the porous shell to reach
the yolk-sac (Brinkmann 2). In Seps chalcides, a reptile, the insufficient
supply of yolk is added to by a uterine secretion containing
degenerated cells and blood derivatives, the outer layer of the
blastocyst being distinctly phagocytic (Giacomini 3). But in the
Sauropsida no union takes place between the maternal tissues and
the foatal membranes, and so in one order of Mammals, the
Ornithodelphia,4 where the young develop outside the body. In all
the other orders the wall of the yolk-sac comes into relation with the
uterine wall over a greater or less area, depending on the extent to
which the mesoblast, spreading round the wall of the blastocyst,
splits into two layers. In the non-mammalian Vertebrates, the
mesoblast and the ceelom extend completely round and the yolk-sac
is entirely separated from the surface layer; so in the sheep and
man. In others (e.g. the rabbit) the coelom does not spread so far.

It still remains to consider the path by which the nutriment is
conveyed to the embryo. In partial extension of the area vasculosa,
the wall of the yolk-sac consists of three parts, each with different
relations (see Fig. 102) : (1) The non-vascular part, with a two-
layered wall of epiblast and hypoblast ; (2) the vascular part, where
the mesoblast is unsplit, e.g. in the opossum — the mesoblast splits in
its entire extent in the rabbit ; (3) the part opposite the ceelom. In
all three parts the trophoblast is bathed by the uterine secretion

1 Balfour, Comparative Embryology, London, 1881.

2 Brinkmann, " Histologie, Histogenese und Bedeutung der Mucosa Uteri
einiger Viviparer Haie und Rochen," Mitt. a. d. Zool. Stat. z. NeapeL, vol. xvi.,
1903.

3 Giacomini, " Ueber die Entwicklung von Seps Chalcides," Anat. Anz., vol.
vi., 1891.

4 Or Monotremata.

416 THE PHYSIOLOGY OF REPRODUCTION

after the disappearance of the prochorion. In the non-vascular part
it is probably transmitted through the liypoblast cells to the yolk-sac,
whence, in turn, it reaches the embryo either by the vitelline vessels
or the developing alimentary canal. In the vascular part the same
may occur, or the nutriment may be conveyed to the embryo directly
by the vessels of the area vasculosa. It is in this region that the
foetal circulation is brought close to the maternal, and gaseous
exchanges may be effected. Opposite the coelom the trophoblast is
lined by a thin layer of non-vascular somatopleur, through which

transference of material to the
coalomic cavity is possible. This
part is subsequently connected
with the embryo by the allantoic
vessels. When the yolk-sac is
entire!}' separated from the
outer wall, nutritive substances
may also be transmitted to the
coalomic cavity and then to the
embryo or yolk-sac.

The nutritive importance of
the yolk-sac may now be con-
sidered in greater detail in
several orders of Mammals.

-Mes.

FIG. 102. — Diagram to illustrate the
three parts of the wall of the yolk-
sac in the rabbit. (From Minot's
Human Embryology, by permission
of William Wood & Co.)

. 1 1, Allantois ; Apl, area placentalis ;
EC, ectoderm ; Mes, mesoderm ;
Ent, extra - embryonic entoderm ;
C'ce, coelom ; En, entodermic cavity
of the embryo ; pro. A, proamnion.1

MABSUPIALS. — In the opossum
the mesoblast spreads about
half-way round the wall of the
blastocyst, but it does not split
over its whole extent. Hence
the ccelom is small, and cor-
respondingly the separation of
the yolk-sac and trophoblast is insignificant (Fig. 103), The
allantois grows out into the coelom only to impinge on and
invaginate the wall of the yolk-sac. It never comes in contact with
the outer wall of the blastocyst. The part of the wall where the
mesoblast is unsplit is thrown into folds which fit into corresponding
furrows of the mucosa. Hence an avillous yolk-sac placenta is formed
(Selenka2). The nutrition in the uterus is very primitive. The ova
contain a comparatively large supply of yolk granules for the initial
stages of development. As they travel along the oviduct and into
the uterus, they are invested with a thick nutritive layer, derived

1 The name proamnion is given to that region of the amnion below the head
of the embryo from which the mesoderm is absent. In Marsupials this may

]>ersist

2 Selenka, Studien iiber die Entuicklungsgewhiehte dcr T/tiere, Wiesbaden.

FCETAL NUTRITION: THE PLACENTA 417

from the secretion of the tubal and uterine glands. Later the
embryos are also nourished by the primitive placental structures for
a period short in duration, but long enough to allow of the differentia-
tion of their main organs and systems. In the mucosa the surface
epithelium remains intact. The only change is an oedema of the
layers, and the sole nutritive material is a watery fluid, composed of
glandular secretion and a lymph transudate almost devoid of cells.
It is absorbed by the trophoblast cells, which here and there enlarge
to enormous " Nahrzellen " and so increase the absorbing surface.
After eight days the food supply becomes inadequate for the developing
embryos, and they are transferred to the pouch and nourished by the
mammary secretion.

EC mes

Cho

J\— Pro.am

Ent

FIG. 103. — Diagram of an opossum embryo and its appendages. (From Minot.)

All, Allantois ; Yk, cavity of yolk-sac ; Coe, coelom ; Am, amnion ; Pro.am,
proamnion ; Emb, embryo ; EC, ectoderm ; Ent, entoderm ; mes, rneso-
derm ; s.t, sinus terminalis ; Cho, chorion (diplo-trophoblast).

In Dasyurus the allantois is vascular over a small area and comes
in contact with the diplo-trophoblast (Fig. 104). But the allantoic
vessels degenerate rapidly and completely, and the allantois .again
lies free in the coelom. In the region of the area vasculosa the wall
of the yolk-sac adheres to the uterine epithelium, and, as in the
opossum, forms a simple yolk-sac placenta. The superficial capillaries
of the mucosa, which are slightly dilated, are separated from the
vitelline vessels by the uterine epithelium and a thin layer of foetal
ectoderm. Through the two layers the gaseous exchange probably
takes place. Beyond the sinus terminalis, the non-vascular part of
the wall unites over an annular zone with the uterine epithelium by
enlarged ectodermal cells. These syncytial "Nahrzellen" are
phagocytic, and enclose fragments of epithelium and superficial
capillaries. Maternal blood is effused and lies in a space between

4i8

THE PHYSIOLOGY OF REPRODUCTION

the ectoderm and eutoderm, whence it is transmitted to the cavity
of the yolk-sac and serves for nutriment (Hill1). The gestation
period is about eight days, as in the opossum.

In Perameles the placental structures are better developed (Hill 2).
Before the attachment of the blastocyst, the uterine mucosa under-
goes preliminary changes. The capillaries increase in size and new
vessels are formed ; the interglandular tissue is composed of a loose
network of anastomosing cells and 'the inter-spaces are filled with

bil ompli

proa I

vascomph.
amn.

-yspl

all

FIG. 104. — Diagram showing the arrangement of the foetal membranes in DosyunM.
(From Hill, " On the Fretal Membranes, Placentation, and Parturition of
the Native Cat (Dasyurus viverfimis)" Anat. Anzeig., vol. xviii., 1900.

amn, Trunk amnion ; all, allantois ; bil.omph, bilaminar omphalopleur ; ck,
chorion (diplo-trophoblast) ; coe, extra-embryonic splanchnocele ; proa,
proamnion ; proa.l, posterior limit of proamnion ; s.t, sinus terminalis ;
vasc.omph, vascular omphalopleur ; y.c, cavity of yolk-sac ; y.s, yolk-stalk ;
y.spl, invaginated yolk-sac splanchnopleur : the ectoderm is represented by a
thin line, the entoderm by a dotted line, and the mesoderm by a thick line.

lymph, the glands increase in length and diameter, and the cells of
the surface epithelium lose their boundaries, and fuse to form a
syncytium analogous to the symplasma of higher forms (see p. 445).

Opposite the coelom, the blastocyst becomes attached to a discoidal
area of the uterine symplasma by means of enlarged ectodermal cells,
and later its wall is vascularised by the allantois. Outside the disc,
the part corresponding to the area vasculosa is also attached by an
annular zone, and a yolk-sac placenta is formed. The non- vascular

1 Hill, " On the Foatal Membranes, etc., of the Native Cat (Dasyurus viver-
rinus)" Atiat. Am., vol. xviii., 1900.

4 Hill, " The Placentation of Peram/iles," (^uar. Jour. Micr. Science, vol. xl.,
1898.

FCETAL NUTRITION: THE PLACENTA

419

part of the wall is bathed by the uterine fluid as in the opossum
(Fig. 105).

In the discoid area a fuctional allantoic placenta is developed.
The ectodermal giant-cells, like the early trophoblastic proliferation
in man, disappear, and the allantoic vessels become firmly attached
to the symplasma into which the maternal vessels penetrate. A
regular interlocking of maternal and fo?tal tissues is produced, and

amn

coe

vase.

omph I'

st

bil omph.

FIG. 105. — Diagram showing arrangement of foetal membranes in Peram-eles.
(From Hill, "The Placentation of Perameles," Quar. Jour. Micr. Science,
vol. xl., 1897.)

amn, Amnion ; all.c, allantoic cavity ; all.mes, allanto-chorionic mesenchyme ;
all.s, allantoic stalk ; bil.omph, bilaminar omphalopleur ; ch, marginal zone
of true chorion around the allanto-chorionic area ; coe, extra-embryonic
coelom ; coe.w, inner or chorionic wall of allantois ; proa.r, persistent
remnant of proamnion ; st, sinus terminalis ; vasc.omph, vascular omphalo-
pleur ; y.c, yolk-sac cavity ; y.spl, invaginated yolk-sac splanchnopleur ;
ectoderm represented by thin line, mesoderm by dotted line, entoderm by
thick line.

the two systems of blood-vessels are separated at the most by a thin
layer of symplasma. It is not yet determined whether the yolk-sac
placenta is functional till birth. According to Hill the wall probably
breaks up before the end of pregnancy. The allantoic placenta, on
the other hand, remains active, and at the time of birth some
maternal tissue is shed, while part of the foetal tissue is left behind.
The gestation period is about eight days.

The allantois in Perameles is of greater importance than in the
opossum or Dasyuriis ; but, relatively to the yolk-sac, it plays a small

420 THE PHYSIOLOGY OF REPRODUCTION

part in the nutrition of the embryo, as evidenced by the fact that the
vitelline vein is thrice as large as the allantoic vein.

UNGULATA. — In the sheep the blastocyst elongates early, and
contains at one part the thickened embryonic area or shield (Fig. 106).
From it the mesoderm reaches out on all sides. As it spreads between
the epiblast and hypoblast, the coelom is developed in it. By the
thirteenth day one-third of the circumference is surrounded by
coelom, and in this area the yolk-sac is separated from the outer wall.
At the seventeenth day the separation of the yolk-sac is complete all
round (Bonnet1). It continues, however, to grow pari passu with
the blastodermic vesicle, and is gradually pushed to one side by the
enlargement of the coelom. At the twenty-fifth day it is reduced to
a solid rod of cells with a few blood-vessels on its outer surface
(Fig. 107), and it disappears before the end of pregnancy (Assheton 2).
The allantois grows out into the coelom very early and expands with

FIG. 106. — Elongated blastocyst of sheep at thirteenth day of pregnancy. (From
Hertwig's Entwicklungsgeschichte des Menschen und der Wirbelthiere, by per-
mission of Gustav Fischer.)

bl, Blastocyst ; e, embryonic shield.

extraordinary rapidity, occupying most of the cavity of the blasto-
dermic vesicle. Its further developments are described later (p. 430).
Hence in the sheep, and in the pig and cow, in which the conditions
are similar, the yolk-sac is functional only from the first appearance
of the vessels in the area vasculosa till about the twentieth day
of pregnancy.

In the horse there is no indication of an allantoic diverticulum
at the middle of the third week, but at the end of the third week
there is a considerable mass of. vascularised allantoic mesoderm at
the caudal end of the embryo into which a small allantoic diverti-
culum extends from the hind gut (Ewart 8).

CARNIVOEA. — The mesoblast and coelom extend completely round
the blastocyst, and the vitelline circulation is active only in the early

1 Bonnet, "Beitrage zur Embryologie der Wiederkauer," Arch. f. Anat. u.
Physiol., 1889.

2 Assheton, " The Morphology of the Ungulate Placenta," Phil. Trans. Hoy.
>S'oc., London, Ser. B., vol. cxcviii., 1906.

3 Ewart, "Studies on the Development of the Horse : I. Development during
the Third Week," Trans. Roy. Soc. Edin., vol. li., 1915.

FCETAL NUTRITION: THE PLACENTA

421

Tr

AS

A.

stages. In the dog the yolk-sac is large and extends -at first to the
end of the citron-shaped ovum (Fig. 123). According to Bischoff *• it
persists till birth, but this is denied by Duval.2 The allantois grows
out on the dorsal side of the embryo, and fuses with the diplo-
trophoblast over a small discoidal area. Later, as the cavity of the
allantois enlarges, it adheres to the whole of the blastocyst wall
except the poles. Subsequently the
zone of adhesion is reduced in extent
(see p. 444).

PROBOSCIDEA and HYRAX. — The
elephant and the aberrant genus Hi/rax
have at full-time, like the Carnivores,
a zonary placenta, but little is known
regarding the development of the foetal
membranes. Assheton3 has recently
given an account of two early embryos
of Hyrax. In the younger, the yolk-sac
occupied about three-quarters of the
surface of the blastocyst, and the
allantois the remaining quarter, the
ovum possibly being wholly embedded
in the uterine inucosa. The yolk-sac
was covered with a network of vessels,
and the head of the embryo dipped

into it. It was invested externally FIG. 107.— Transverse section
with a mass of trophoblastic cells,
honeycombed with spaces and filled
with maternal blood, but no villi were
developed. In the second embryo the
yolk-sac was much reduced, and was
" presumably enveloped by the allantois."
It had previously been shown by Turner
that the yolk-sac disappeared at an
early period.

through the blastocyst of
the sheep at the twenty-
fifth day. (From Assheton,
"The Morphology of the
Ungulate Placenta," Phil.
Trans. Roy. Soc., London,
Ser. B., vol. cxcviii., 1906.)

A., Allantois ; A.S, splanch-
nopleur of allantois ; A.V,
allantoic blood-vessel ; C,
crelom; V, commencing' folds
from which villi spring ;
Y, solid yolk-sac.
RODENTIA. — In Rodents the condi-
tions are entirely different. The mesoblast never extends, in the
rabbit, rat, or mouse, completely round the ovum, and the yolk-
sac hypoblast remains long in contact with the trophoblast, and
carries on the nutrition of the embryo till the tardily formed
allantoic placenta is developed. Regarding the partial extension

1 Bischoff, Entwickdungsgeschichte der Saugethiere und des Menschen, 1842.
Duval, "Le Placenta des Carnassiers," Jour, de PAnat. et de la Phys.,

1893.

3 Assheton, Phil. Trans. Roy. Soc., London, loc. cit.

422

THE PHYSIOLOGY OF REPRODUCTION

Ent

of the mesoblast, Minot l says : " That it represents a modified
condition is evident, since in all non-mammalian Vertebrates both
mesoderm and coelom extend completely round the yolk. Hence
the complete separation of the yolk-sac in man and the sheep is
nearer the ancestral type than the relations of the extra-embryonic
germ-layers to one another in the rabbit and opossum."

In the rabbit the mesoblast begins to spread out from the
embryonic region about the end of the first week of gestation, and
it gradually reaches half-way round the circumference of the blasto-
cyst. It splits into two layers over its whole extent, and it is
limited below by the sinus terminalis (Fig. 108). The lower half
of the yolk-sac is non-vascular,' and its wall of hypoblast is closely

invested by trophoblast. Later the
yolk-sac begins to shrink, taking a
mushroom shape, and its vascular
*half conies against the non-vascular
half (Fig. 109). The specially large
coelomic 'space, thus left by the
shrinking of the vesicle, is filled
with fluid through which the
allantois extends to reach the part
of the wall not covered by the
yolk-sac. Hence at this stage the
whole wall of the blastocyst is
vascularised, one-half by the vitel-
coe, Coelom ; Cho, chorion (diplo- line and the other half by the
trophoblast) ; Yt, yolk-sac ; me*, allantoic vessels.2
, mesoderm ; v.t, vena terminalis ;
Ent, entoderm ; EC, ectoderm. From an investigation of the

early stages in the mouse and rat,

Robinson3 attaches much importance to the yolk-sac in providing
for the nutrition of the embryo. On the seventh day the yolk-sac
is large, and becomes invaginated with the inversion of the germinal
layers (see p. 468). Outside its thin .wall lies extravasated maternal
blood, which is absorbed into the cavity. Over a large area the
wall of the yolk-sac becomes villous with a covering of columnar
hypoblast. Over a small area the trophoblast is thickened and
maternal blood circulates in its spaces. But the allantois has not
yet come in contact with it, and the blood " must serve only for
the nutriment of the trophoblast itself." At the eleventh day the
trophoblast is vascularised by the allantoic vessels, by which the
nutriment is now transmitted as well as by the vitelline vessels in

1 Minot, Human Embryology, Boston, 1892.

2 Hertwig, Entwicklungsgeschichte des Menschen und der Wirbelthiere, 1906.

3 Robinson, "The Nutritive Importance of the Yolk-Sac," Jour, of Anat. and
Phys., vol. xx vi., 1892.

EC

FIG. 108. — Blastodermic vesicle of
the rabbit. (Minot.)

FCETAL NUTRITION: THE PLACENTA

423

the yolk-villi. Then the yolk-sac becomes less important. The
circulation in the decidua reflexa, which surrounds it, decreases and
ceases altogether on the sixteenth day, and the wall of the yolk-sac
becomes thin and bloodless. " At the same time numerous diverticula
grow out from the entodermal sinus into the hilum of the allantoic
placenta, and these may still absorb nutriment though they are more
probably excretory." Later the outer wall of the invaginated yolk-
sac undergoes atrophy and completely disappears. The remains of
the yolk-sac cavity are in
this way bathed in the uterine
fluids. At the same time the
villi of the inner wall increase
in size and complexity, but
whether they absorb the fluids
or are entirely excretory is
uncertain.

In the spiny mouse
(Acomys caharinus), Assheton l
found in a well-advanced
pregnancy that the yolk-sac
was still extremely vascular,
and covered with a columnar-
celled epithelium which was
much folded. The blood-

A •

vessels lay in the folds, and
so approached closely to the
placenta. The yolk-sac was
firmly attached to the
placenta over the peripheral
area, but not so closely as
described above for the rat

FIG. 109. — Diagram of the blastodermic
vesicle of the rabbit in longitudinal
section. (From Hertwig's Entwick-
IwngsgescJiichte des Menschen und der
Wirbelthiere.}

e, Embryo ; a, amnion ; a^, allantois with
blood-vessels ; f.d, vascular layer of
mushroom-shaped yolk-sac ; d.s, cavity
of yolk-sac; s.t, sinus terminalis; y,
large space filled with fluid.

and common mouse. In the

spiny mouse the folds do not become involved in the placental

tissues.

The preplacental blastocyst in the beaver has been investigated
by Willey2 who states that its most conspicuous feature is the
presence of a deep tract of mesoblastic origin along the length of
its embryonic side. This is comparable to the " Haftstiel " of Tarsius,
monkeys and man (see pp. 490 and 500). This structure continues
to grow in later stages, and by accession of material from the uterine
mucosa becomes converted into the definitive umbilico-uterine con-

1 Assheton, " On the Foatus and Placenta of the Spiny Mouse," Proc. Zool.
Soc., London, 1905, vol. ii.

2 Willey, " The Blastocyst and Placenta of the Beaver," Quar. Jour. Micr.

-<>, vol. lx., 1914.

424 THE PHYSIOLOGY OF REPRODUCTION

necting membrane. In origin it is a non-vascular somatopleur or
diplo-trophoblast, but in the mature foatal sac there are intrusive
capillaries proceeding into it from the vascular area. Willey suggests
that the reason for the existence of the connecting membrane supple-
menting the placental implantation in the attachment of the foetal
sac is to be sought in the semi-aquatic habits of the beaver, which
retains its activity, swimming under the ice to procure food from
the submerged stock of winter provender throughout the period of
gestation. Were it not for the additional support of the connecting
membrane the narrow deciduous root of the massive placenta might
be torn asunder.

INSECTIVOKA. — In the hedgehog the yolk-sac forms a placenta
which nourishes the embryo until the mesoblast splits into two
layers and the allantoic placenta is formed. At a very early stage
the epiblastic wall of the blastocyst has spaces in which maternal
blood appears. As the mesoblast spreads out in a single layer, the
area vasculosa develops, and its branches, contained in mesoblastic
warts and ridges, interlock with the adjacent trophoblast to form
yolk-villi (Fig. 110). The yolk-sac or omphaloidean placenta reaches
its full development at the time when the allantois comes in contact
with the trophoblast (see p. 480). Then the yolk-sac is gradually
separated from the wall, more and more of its villi being peeled out
from the trophoblast as the separation increases. The vitelline
circulation .at the same time diminishes, though it never ceases
entirely (Hubrecht 1).

In the shrew the yolk-sac adheres by a zonary strip to lateral
cushions of proliferated mucosa, but the resulting yolk-sac placenta
is avillous (Hubrecht 2). The trophoblast is again thickened, and in
its spaces maternal blood appears, but at a later date than in the
hedgehog. The maternal blood is bodily absorbed, and at the same
time the yolk-sac contains a characteristic yellowish-green, glassy
coagulum with granules in it. Later the mucosal cushions disappear
and the adjacent trophoblast thins (see p. 483).

In the mole a simple yolk-sac placenta persists throughout
pregnancy (Robinson3). Unlike the hedgehog and the shrew, in
which the gland lumina are plugged by the trophoblastic syncytium,
there is in the mole a copious glandular secretion containing
degenerated cells, which is absorbed by the trophoblast (see p. 484).

Tupaia javanica differs from the other Insectivora in having a
temporary yolk-sac placenta formed in the same situation as the

1 Hubrecht, "The Placentation of Erinaceus europceus" Quar. Jour, ^ficr.
Science, vol. xxx., 1889.

2 Hubrecht, " The Placentation of the Shrew," Quar. Jour. Micr. Science, vol.
xxxv., 1894.

3 Robinson, Hunterian Lectures, loc. cit.

FCETAL NUTRITION: THE PLACENTA

425

allantoic placenta subsequently occupies (see p. 486). The same
occurs in the bat (p. 489).

PRIMATES. — In monkeys, old- and new-world, there is no decidua
reflexa, and a portion of the trophoblast is in contact with the
uterine fluids. But even in Selenka's earliest specimens of monkeys
and apes, the yolk-sac is a small, closed sac attached to the ventral
surface of the embryonic area, and is entirely separated from the
trophoblast. The embryonic area is connected with the inner surface

; , ,, . 1 llantoidean region

of trophosphere

Omphcdoidean

region of
trophosphere

Decidua reflexa

__ Uterine
**"'' lumen

FIG. 110. — Diagram to illustrate the fcetal membranes of Erinacev.s. (From
Hubrecht's "The Placentation of Erinacetis europreus" Qtuir. Jovr. Micr.
Science, vol. xxx., 1889.)

of the chorion by a short stalk of mesoderm, in whicli the
vessels run.

In the youngest human ovum yet examined, the yolk-sac is also a
small, closed vesicle, separated from the trophoblast by a single thick
layer of mesoblast (Fig. 111). The splitting of the mesoblast occurs
very early, even before the appearance of the primitive streak, and
the ccelom spreads round the whole circumference of the ovum. The
earliest vessels appear 011 the under surface of the sac, and gradually
extend over its upper pole, until the whole sphere is covered by a
vascular network. The vessels are in direct continuity with vessels
which develop in the connecting-stalk (see p. 490), and through them
with the vessels of the chorion by a vascular loop, the sinus ensiformis

14 A

426

THE PHYSIOLOGY OF REPRODUCTION

of Eternod (Bryce1). This communication appears to exist before
any vessels appear in the embryo itself. From the third week
onwards, saccular dilatations of the entodermal lining of the yolk-sac
are produced, and from their walls solid masses of cells are budded
off, resembling liver-tissue in its simplest form and perhaps function-
ing as such (von Spee 2). The sac grows up to the end of the fourth

FIG. 111. — Hypothetical section of the human ovum embedded in the decidua,
somewhat younger than Peters' ovum. The trophoblast is greatly
thickened, and lined with mesoderm, which surrounds also the embryonic
rudiment, with its yolk-sac and amnio-embryonic cavity (T. H. Bryce in
Quain's Anatomy). The embryonic rudiment is proportionally on too
large a scale.

week. It is then pear-shaped, and is united to the intestine by a
long neck in which the cavity is obliterated. The vesicle persists
throughout pregnancy. Little is known of its contents ; at the end
of pregnancy it contains variable quantities of fatty substances and
carbonates (Schultze 3).

1 See Quain's Anatomy, vol. i., Part I., 1908.

2 Ibid.

3 Schultze, " Ueber die Embryonalhiillen und die Placenta der Saugethiere
und des Menschen," Sitzungsb. d. Wiirzbvrger physik.-med. (resell., 1896.

FCETAL NUTRITION: THE PLACENTA 427

III. THE PLACENTA IN INDECIDUATA

In the placental Mammals an. attachment takes place between
maternal and foetal tissues in the uterus, and the trophoblast is
vascularised, except in the Primates, by the allantois. The method
of attachment varies in different orders, and sometimes in different
groups of an order. In the Indeciduata, however, the first attach-
ment is always obtained by an apposition of the trophoblast to the
surface of the mucosa.

UNGULATA : Pig. — In the pig the blastocysts are spherical till the

FIG. 112. — Portion of the injected chorion of the pig. The figure shows a
minute circular spot (ft), enclosed by a vascular ring, from which villous
ridges (?•, r) radiate (Turner). (From Balfour's Comparative Embryology,
vol. ii. By permission of Messrs. Macmillan & Co. Ltd.)

tenth day. Then they rapidly elongate, and by the fourteenth day
they fill the whole length of the uterus. Subsequently they obtain a
greater surface of contact by a series of concertina-like foldings
(Assheton :), which fit between ridges of the uterine mucosa. The
ridges are inter-glandular in position (Fig. 112), radiating from small
circular spots, twenty or thirty to the square inch, which represent
the gland-mouths (Turner2). It is usually stated that the uterine
surface epithelium remains intact ; but Assheton has recently proved
that it shows signs of degeneration as early as the eighth day,
and at the eighteenth day is reduced to a thin layer. Three days
later, however, it again appears normal and is formed of long
columnar cells, to the ends of which the trophoblast fits closely,

1 Assheton, Phil. Trans., loc. cit.

2 Turner, Lectures on the Comparative Anatomy of the Placenta, Edinburgh,
1876.

428

THE PHYSIOLOGY OF REPRODUCTION

sending protoplasmic processes between the cells (Fig. 113). These
processes may even reach past the epithelium to the underlying layer
of dilated capillaries (Robinson), and absorb nutritive material or
effect gaseous exchanges.

The trophoblast is single-layered throughout, and, after the first
three weeks, forms a syncytium. Internally to it lies the mesoblast,
which in the main follows its ridges and furrows, but occasionally
bridges across a fold. It is vascularised by the vessels of the
allantois, which completely surrounds the embryo. The gland-
mouths lie along the course of the vessels (Assheton). No formation
of villi takes place, and the attachment never goes beyond the
stage of apposition except for the protoplasmic extensions of the
trophoblast (Fig. 114).

Blv

mes

EP

FIG. 113. — Section through the wall of the uterus and the blastocyst of the
pig at the twentieth day of pregnancy (Assheton).

mes, Mesoblast ; BLv, foetal vessel ; TV, trophoblast ; Ep, long columnar
epithelium of uterine surface.

The uterine mucosa contains no special cotyledonary areas such
as are found in the sheep and cow. The surface epithelium, though
it shows the degenerative changes already referred to, is apparently
never completely destroyed. The glandular epithelium does not at
any time show signs of degeneration. It secretes actively during
the early stages, and probably during the whole of pregnancy. As
in the sheep and one of the lemurs (Galago agisymbanus), the glandular
orifices are covered by domes of trophoblastic cells, which absorb the
secretion and transmit it as nutriment for the developing embryo by
the allantoic vessels. The sub-epithelial tissue is gelatinous, and
early in pregnancy it begins to increase in thickness by a widening
of the lymphatics and blood-vessels and a new formation of capillaries.
The constituents of the nutriment provided for the embryos are
referred to later (see p. 432).

Mare. — In the mare the details of placental development are not

FCETAL NUTRITION: THE PLACENTA 429

yet known. In the early stages the blastodermic vesicle is attached
to the uterine mucosa by the trophoblast covering the lower pole of
the ovum. The trophoblast at the end of the third week differs from
that of the sheep and pig and other Ungulates. Up to the sinus
terminalis it consists of typical columnar cells; beyond the sinus
there are (1) groups of tall columnar cells arranged to form discs
which probably help to fix the blastocyst to the lining of the uterus ;^
(2) groups of columnar cells in process of elongation ; and (3) phago-
cvtic columnar cells with sac-like processes placed around the discs
and especially in shallow depressions beyond the sinus terminalis
which probably lie opposite the openings of the uterine glands and
are concerned in taking up the more solid particles of uterine milk
(Ewart1).

Uff

FIG. 114. — Diagram representing a stage in the formation of the placenta of
the pig. (From Eobinson, Hunterian Lectures, Jour, of Anat. and
Phys., vol. xxxviii., 1904.)

UM, Uterine muscle ; MB, maternal blood-vessel ; UG, uterine glands ;
UE, uterine epithelium ; FE, foetal ectoderm ; FM, foetal mesoderm.

Villi are formed in the allantoic region, and they fit into crypts
which are probably lined with maternal epithelium. Between the
foetal and maternal tissues in the crypt is a space filled with secre-
tion. The lymphatic system of the mucosa is enormously developed
(Kolster 2).

Sheep. — In the sheep and cow the poly-cotyledonary type of
placenta is found. The former is determined by the presence from
an early period, and independently of pregnancy, of numerous
prominences or cotyledonary burrs, which project as thickened knobs
of the sub-epithelial tissue into the uterine lumen. During preg-
nancy they form connections with localised proliferations of the
trophoblast. The burrs vary in number from fifty or sixty in the
sheep to five or six in the roe-deer.

The ova of the sheep reach the uterus four or five days after

1 Ewart, Critical Period in the Development of the Horse, London, 1897 ; and
i' Studies in the Development of the Horse," Trans. Roy. Soc. Edin., vol. li.,
1915.

2 Kolster, " Die Embryotrophe placentarer Sauger, mit besonderer Beriick-
sichtigung der Stute," Anat. ffefte, vol. xviii., 1902.

430

THE PHYSIOLOGY OF REPRODUCTION

coitus, and the blastodermic vesicles remain free till the seventeenth
day. Then the attachment to the mucosal surface begins, and it is
completed by the thirtieth day (Assheton). After the ninth day,
when the prochorion ruptures, the trophoblast comes in contact with
the uterine epithelium. Apparently, as the result of this, the
absorption of nutriment is easier, and the blastodermic vesicle
increases rapidly in size so as to fill the uterine horn, or both horns
if only one embryo is present.

Certain changes occur in the mucosa before attachment. The
leucocytes, which in the non-pregnant uterus are situated at the
base of the lining epithelium, increase in number and penetrate
between the epithelial cells. The glandular sacs, situated at the
junction of the branches with the main ducts, expand greatly and
actively secrete. It is generally held that the surface epithelium

sir

FIG. 115. — Section through the uterine and embryonic parts of a cotyledon of the
sheep at the twentieth day of pregnancy. Folds in the trophoblast fitting
into sulci of the cotyledonary burr. (Assheton.)

mes, Mesoblast ; tr, trophoblast ; us, degenerated uterine epithelium ;
str, uterine stroma.

is not destroyed, but Assheton has shown that on the cotyledonary
burrs it is distinctly degenerated by the seventeenth day, and he
has also brought forward strong evidence that it is not subsequently
regenerated, but is replaced by binucleate cells of the foetal ectoder-m.
In the cotyledonary areas of the trophoblast, villi are developed
as buds of epiblast, which afterwards contain cores of mesoblast with
branches of the allantoic vessels (Fig. 115). They fit into depressions
or crypts on the surface of the cotyledons, increase in length, and
branch in different directions. Whether they literally grow into
the maternal tissues either mechanically or by a phagocytic action
is uncertain.1 It seems more likely that very little, if any, further
penetration occurs, but that the sub-epithelial tissue swells and keeps
pace with the villi as they increase in length. The crypts, if their
lining cells really belong to the foetal ectoderm, are not secretory,

1 At this stage Assheton did not observe any actual engulfuient of cells, but
considered that nutriment might be transmitted by fine processes of the binu-
cleate cells which united with similar processes of the connective tissue cells of
the mucosa.

FOETAL NUTRITION: THE PLACENTA

431

and there is no free space, such as is described in the mare, between
them and the villi. The sub-epithelial tissue is represented in the
non-pregnant uterus by a thin layer of dense connective tissue, with
localised thickenings in the burrs. With the onset of pregnancy
occur an infiltration of lymph between the more superficial cells
of the sub-epithelial layer, and an increase in the number and size
of the blood- capillaries and lymphatics. Thus the layer becomes
spongy and swells up around the foetal villi, producing the cotyle-
donary interdigitation. At the fimdus of the crypts the lining cells

m.v

Tr

FIG. 116. — Section through the base of a foetal villus and the apices of two inter-
crypt columns. Sheep. The surfaces of the columns are traversed by
large blood-vessels, which later rupture and form the blood-extravasations.
(Assheton.)

Tr, Trophoblast dipping into crypt ; Ic, inter-crypt column ; m.v, maternal

blood-vessel.

become syncytial. At the apices of the inter-crypt columns lacunae
of maternal blood are formed by repeated small haemorrhages from
the superficial capillaries (Fig. 116).

In the inter-cotyledonary area, the epithelium, whether or not it
degenerates over large areas in the early stages as Assheton supposes,
is later healthy and vigorous. There is no formation of a spongy
layer in the sub-epithelial tissue as in the burrs. But a great change
occurs in the glands, which are wholly inter-cotyledonary in position.
They increase in length and complexity, and secrete actively. Towards
the end of pregnancy, however, the greater part of the uterine glands
is destroyed, but the surface epithelium still secretes. At the upper
end of each horn the wall of the blastocyst forms a crumpled

432 THE PHYSIOLOGY OF REPRODUCTION

structureless membrane with no trace of nuclei, while the uterine
mucosa in this region is thrown into folds and covered with a high
columnar epithelium which is very active. The secretion is apparently
transmitted by transfusion through the membranous wall, and is
found inside the sac. At full time this part of the mucosa shows
signs of great degeneration, resembling the pulpe diffluente of Duval
in the guinea-pig (Assheton). The inter - glandular cells also
hypertrophy like the connective tissue cells of Rodents.

The development and structure of the placenta of the sheep have
been described at some length because the formation of the special
nutriment for the foetus has received close attention in that
animal.1

C.ow. — In the cow (Fig. 117) the placenta has essentially the same
form as in the sheep, but the interlocking is not so firm. On separation
of the maternal and foetal parts of the cotyledons, the former are
found to comprise the larger part. In the fully developed sheep's
placenta the foetal parts constitute the main mass of the cotyledon.
The various stages of development have not been completely investi-
gated, but one other difference has been noted, viz/ the absence of
lacuiue of maternal blood at the bases of the villi (Ledermann 2).

The chorionic sac extends into both uterine cornua.

The inter-cotyledonary trophoblast is avillous in the sheep and
cow. In the giraffe, however, there are rows and clusters of villi in
addition to the cotyledonary villi. Simple villi between the cotyledons
are also found in Ccrvus, Orcas, and Tetraceros?

The Uterine Milk •

The existence of a nutritive juice in the uterus of Ruminants
during pregnancy has been recognised since the days of Harvey. He
spoke of an albuminous fluid, which might be squeezed out from the
cotyledons of the placenta, as a source of nutriment for the foetus.
As to its origin, he says in one of his Letters : " It might be transported
by the uterine arteries and distilled into the uterus." The fluid was
first called uterine milk by Needham in 1667. Haller described it as
a secretion of the utricular glands, and this view was supported by
Bischoff, Sharpey, and others, who considered it the immediate store

1 For the above account of the development and structure of the sheep's
placenta, we are largely indebted to the important memoir of Assheton. Differ-
ing in many respects from previous descriptions, it alone brings forward evidence
that the Ungulate placenta may be "secondarily simplified" in Hubrecht's
sense (see Quar. Jour. Micr. Science, ] 908).

2 Ledermann, " Ueber den Ban der Cotyledonen im Uterus von Bos, etc.,"
Inaug.-Dis., Berlin, 1903.

3 Turner, "On the F<etal Membrane of the Eland (Oreas canna)" Jour, of
Anat. and Pkys., vol. xiv., 1879. Weldon, " Note on the Placentation of
Tetraceros quadricomis" Proc. Zool. #oc., 1884.

FCETAL NUTRITION: THE PLACENTA

433

of foetal nutriment. It was analysed by Gaingee,1 who showed that
the fluid contained a large amount of protein and fat and some salts,
and was thus well adapted for nutrition.

• But Haller's view of its origin was not accepted by Turner 2 and
Ercolani.3 Turner showed that during pregnancy new crypts were
formed in the cotyledons, and he supposed that the uterine milk
represented the secretion of these crypts. Ercolani went even further
and stated that such a secretion existed in all placenta?, but Turner
was strongly opposed to this : " That such a fluid (uterine milk) is

FIG. 117. — Columnar trophoblast-cells from the base of a fa-tal villus of the
placenta of the cow at the third month of pregnancy, to show phago-
cytosis. (From Jenkinson's " Notes on the Histology and Physiology
of the Placenta in Ungulata," Proc. Zool. Soc., London, vol. i., 1906.)

produced in all placenta?, where utricular glands or follicles continue
to secrete during the whole period of placental formation, is very
probable. But in the placenta? of the sloth, the apes, and the human
female, where an unusual development of the maternal blood-vessels
into larger sinuses takes place, a modification in the anatomical
structure is produced which seems to render the presence of such a
secretion unnecessary. The nutritive changes in all probability take
place directly between the maternal and foetal blood."

1 Gamgee, " On the Chemistry and Physiology of the Milky Fluid found in
the Placental Cotyledons of Ruminants," Brit, and For. Med.-Ckir. Review, 1864.

2 Turner, "The Placentation of the Sloths," Jour, of Anat. and Phys.,\o\.
viii., 1874.

3 Ercolani, "SulP unita del tipo anatomico della placenta," Mem. delP Accad.
di Bologna, 1876.

434 THE PHYSIOLOGY OF REPRODUCTION

More recent investigations have thrown fresh light on the origin,
composition, and absorption of uterine milk. It must be recognised
that, even before the onset of pregnancy, changes occur in the uterus
which are important for the nourishment of an embryo developing
later. Shortly before the first oastrous period, the mucosa " matures "
by the formation of the richly cellular sub-epithelial layer of connective
tissue already referred to (see p. 431). Among Indeciduates it is
specially well marked in the cotyledonary types. With the first
prooastrum the mucous membrane becomes cedematous, and the super-
ficial capillaries are dilated. Many of them rupture and give rise to
miliary hiemorrhages, which later undergo changes such as occur in
haemorrhages elsewhere. Whether the changes are caused by an
enzyme action on the part of the leucocytes is uncertain ; but in any
case the white corpuscles take up the pigmented products of dis-
integration, and then arrange themselves in a row, or in groups, close
under the surface epithelium in the manner described in an earlier
chapter (Chapter III., p. 105). Some of the leucocytes contain
unaltered haemoglobin, as is shown by the characteristic reaction with
eosin ; others contain derivatives of it, in which iron may often be
demonstrated. With the onset of pregnancy these cells wander out
between the epithelial cells, and mingle with the secretion lying in
the uterine cavity. This secretion is poured out by the superficial
and glandular epithelium, which becomes more active at the beginning
of pregnancy with the increased How of blood and lymph through the
mucosa. It forms the more fluid part of the uterine milk in which
the formed constituents lie. It is necessarily found only in the extra-
cotyledonary regions since no glands exist in the burrs.

Besides the intracellular pigments, there is another source of iron,
though in widely varying amounts. In all placental Mammals a
greater or less amount of maternal blood is in direct contact with the
trophoblast. In the pig and mare it is restricted to individual red
blood corpuscles, which find their way to the surface and mingle with
the gland secretion. In the ass Strahl * has found blood in greater
amount, forming small effusions. In the sheep its presence has often
been noted by Tafani,2 Bonnet,3 and others. The position of the
extravasations in the placenta has been already referred to (see p. 431).
In the cow they are apparently not a constant phenomenon, the
supply being often restricted, as in the mare, to a few single
erythrocytes. In the deer, blood is effused into the glands, but no
extravasations take place in the cotyledons. Here the whole of the

1 Strahl, see Hertwig's Handb. d. vergl. u. exp. Entwickelungsg. d. Wirbel-
thiere, 1902.

2 Tafani, "Sulle Condizioni utero-placentari della Vita Fetale," Arch, della
Scuola cFAnat.-Pat/t., Firenze, 1886.

3 Bonnet, " Ueber Embryotrophe," Deut. nied. Wock., 1899.

FCETAL NUTRITION: THE PLACENTA

435

maternal part of the burr appears to be digested and absorbed by the
trophoblast. The greater activity of the foetal ectoderm in the deer
is also shown by the destruction of the epithelium over the whole
tmrface of the uterus (Strahl l).

FIG. 118. — Histology of the placenta in the cow and sheep. (From Jenkinson,
Vertebrate Embryology, Oxford, at the Clarendon Press.)

1. Festal and maternal tissues in a cotyledon, tr, Trophoblast of a villus ; the

cells are absorbing fat (black). In the trophoblast are binucleate cells.
Behind it are the connective tissue and blood-vessels of the allantois.
ep, Uterine epithelium lining a crypt. Fat secretion is going on, the ends
of the cells with fat globules being pinched off and thrown into the crypt's
lumen. Below the epithelium are maternal capillaries and connective tissue.

2. Columnar trophoblast cells form between the bases of the cotyledonary villi.

The cells contain ingested matter (corpuscles, nuclear, and cell debris).

3. Ingestion of extravasated maternal corpuscles by the trophoblast in the

sheep. The cells contain pigment besides corpuscles.

4. Deposition of pigment derived from haemoglobin of ingested corpuscles in

trophoblast cells of cow. The pigment granules (black) are deposited in
irregular masses.

In addition to blood, the uterine milk contains fat in large
quantities. Before pregnancy it may be demonstrated in the sub-
epithelial leucocytes which later migrate to the surface. Fat globules
are also contained in large amount in the epithelial cells of the

1 Strahl, "Ueber die Semiplacenta multiplex von Cervus elaphus," Anat.
Hefte, H. xciii., 1906.

436 THE PHYSIOLOGY OF REPRODUCTION

surface and glands. According to Bonnet, it cannot be considered
as a fatty degeneration because the cells are otherwise healthy; it
is rather a fatty infiltration, the epithelium secreting it from the
lymph or blood-plasma, storing it and later giving it off to the
uterine milk. %

Kolster1 has described a process by means of which cellular
elements are added to the " Embryotrophe." 2 The gland epithelium
proliferates so strongly that the cells cannot find room in the wall,
and tracts of them are invaginated into the lumen. Later the
cellular projections, sometimes along with some of the underlying
connective tissue as in the mare, are cut off' and added to the
embryotrophe (Fig. 119).

Traces of glycogen may be extracted from both the maternal and
foetal parts of the cotyledons, but it is too small in amount to be
demonstrated histologically. It is also present in small amounts in the
extra-cotyledonary areas — in the uterine epithelium both superficial
and glandular in the cow, in the sub -epithelial connective tissue in
the sheep, and in the uterine milk (Jenkinson 3). Large quantities
of glycogen are stored in the plaques amniotiques, localised masses of
cells on the internal surface of the anmion, and later on the umbilical
cord. In the calf embryo the plaques reach their full development
about the sixth month, and then gradually atrophy.

It is obvious that the uterine milk must contain many elements
which have not been mentioned individually. The product of
conception requires numerous other substances for its development
besides protein, fat, carbohydrate, and iron. Organic phosphorus
compounds are furnished by the nuclei of cells, and these may also
contain iron. In general the fixation of mineral elements is slight
at the beginning of pregnancy, but becomes active towards the end.
But the requirements vary at different periods of pregnancy. For
example, sodium decreases and calcium increases with the replace-
ment of cartilage by bone, and potassium increases with the
increased manufacture of red blood corpuscles. These and many
other substances are present in uterine milk though not demonstrated
histologically. Either they have been dissolved by the fixative, or
have remained unstained by the methods hitherto employed.

One other constituent has been described by various observers,

1 Kolster, "Die Embryotrophe placentarer Sauger, etc.," Anat. Hefte, vols.
xviii. and xix., 1902 and 1903.

2 Objections have been raised to the term " uterine milk " because the fluid
contains cellular elements, pigment granules, etc., which are not present in the
mammary secretion. Bonnet and his followers have employed the convenient
term "Embryotrophe," but it must be noted that in the sheep it forms the
nutriment long after the embryonic stage of the developing ovum is past.
The two terms are used indiscriminately in this chapter.

3 Jenkinson, " Notes on the Histology and Physiology of the Placenta in
Ungulata," Proc'Zool. Soc., London, 1906, vol. i.

FCETAL NUTRITION: THE PLACENTA

437

but its composition and significance are unknown. Besides the
leucocytes that contain pigment granules and fat, others are filled
with r'od-like bodies, the
" Uterinstabchen " of Bonnet.1
Later they appear in the uterine
milk. Rods have also been de-
scribed in the trophoblast of
the rabbit by Beneden, and
in the uterine mucosa by
Schmidt,2 who stated that they
were composed of calcium oxa-
late. In Ruminants they are
found in enormous numbers, but
whether they form a supply of
calcium for the foetus is not
known (Fig. 121). There is at
present no evidence that they
are "protein crystals," a name
sometimes applied to them.3

1 Bonnet, "Beitra'ge zur Embryo-
logie der Wiederkauer gewonnen am
Schafe," Arch.f. Anat. u. Phys., Anat.
Abth., 1884.

2 Quoted by Bonnet, " Ueber Em-
bryotrophe," Munch, med. Woc/i., 1899.

3 Jenkinson ( Vertebrate Embryo-
logy, London, 1913) has described
" the curious, rounded or elongated,
often flattened, bodies, sometimes
soft, sometimes hard and brittle,
found floating in the allantoic fluid,
and familiar for many centuries
under the title of ' hippomanes.' In
the cow they are white or pale
yellow, in the sheep a dirty brown.
In the sheep they are formed by
local accumulations of the viscid
uterine milk, which get into pockets
of the trophoblast between the
cotyledons. Gradually, pushing the
trophoblast and allantois in front of
them, they make their way into the
cavity of the latter, in which they
lie attached by a stalk to the wall ;
the stalk narrows and breaks, and
they are free in the cavity. At first
they are surrounded by a membrane

— the remains of their covering of allantois and trophoblast — and are soft ; they
are composed of granular coagulable material, full of cell-detritus, degenerating
nuclei, globules of fat and glycogen, and leucocytes. Later the membrane
disappears, and the bodies become hard by being saturated with calcium oxalate
in the form of ' envelope ' crystals. In the cow, when outside the chorion and
still soft, they are a bright orange colour, due to the presence of bilirubin,
doubtless derived from the extravasated corpuscles eaten by the trophoblast ;

FIG. 119. — First stage of cellular secre-
tion in the placenta of the cow.
Invagination of glandular epithe-
lium and some of the underlying
connective tissue. (From Kolster,
" Die Embryotrophe placentarer
Sa'uger," Anat. Jfefte, vols. xviii. and
xix., 1902-03.)

438 THE PHYSIOLOGY OF REPRODUCTION

The uterine milk has thus the following constituents — the
secretion of the superficial and glandular epithelium, perhaps mingled
with lymph transuded from the oedematous mucosa; leucocytes
containing haemoglobin derivatives, fat globules, and " Stabchen " ;
glycogen; tracts of glandular epithelium set free by a process of
"cellular secretion"; red blood corpuscles and their derivatives;
connective tissue elements ; salts, etc., which are in solution and not
recognisable by ordinary histological methods.

While lying free in the uterine cavity, the uterine milk under-
goes changes which consist largely in a disintegration of its cellular
elements. The leucocytes degenerate and their cytoplasm, with the
pigment granules, fat globules, and " Stabchen," is set free. The
tracts of glandular epithelium are also transformed into a mass of
de'bris, and their contents lie free in the embryotrophe. The red
blood corpuscles may be ingested almost unaltered by the trophoblast,
or they may first be laked, and the haemoglobin may. be absorbed as
such, or undergo changes before absorption. According to Jenkinson,
haemoglobin is broken up into an iron-containing and iron-free part.
The former is carried away by the foetal blood-vessels and stored in
large quantities, principally in the foetal liver, as a reserve for use
during lactation. The iron-free part is deposited in the cells as a
pigment, occurring in such amount as to give, especially in the later
stages of pregnancy, a deep brown colour to the fostal cotyledons.
It collects at the apices of the villi, and its presence suggests that
the cotyledons are actively engaged in excretion (Assheton). The
histological changes in the red blood corpuscles absorbed by the
trophoblast have been described by Jenkinson. They are engulfed
by amceboid processes of the cells, and gradually become paler
in colour and irregular in outline ; often they clump together.
Gradually yellowish-brown granules are deposited on the surface
of the included cells, and this process continues till the whole is
converted into a dark brown mass. Bonnet called the granules
hrematoidin crystals, but Jenkinson was unable to demonstrate this
pigment in alcoholic extracts of the placenta. He found two other
pigments, one absorbing a small part of the violet end of the
spectrum, and the other showing two absorption bands, which
differed slightly from those of oxyhaemoglobin in neutral solution
and of haematoporphyrin in acid solution. This pigment is obviously
a haemoglobin derivative, and from it bilirubin may be formed. It
is present in the sheep and cow during pregnancy, but not in the
virgin uterus of the sheep. A similar yellowish -brown pigment

they are, indeed, found at the bases of the villi, just where these extravasations
occur. Large allantoic bodies impregnated with calcium oxalate are found in
the horse'.' (see Fig. 101 above).

FCETAL NUTRITION: THE PLACENTA

439

occurs in the crypts and the tissues outside them, and also, according
to Assheton, in the maternal blood-stream. It is not yet possible
to explain the exact significance of these changes. The iron-free
pigment is apparently a waste product, and the iron-containing part
is stored in the foetal organs. Whether the foetus subsequently
synthesises part of the organic iron compound into hemoglobin, or
absorbs minute quantities of haemoglobin as such, according to its
requirements, is unknown.

The cotyledonary and inter-cotyledonary parts of the placenta
present differences both anatomically and physiologically. In the
inter-cotyledonary region are the glands, and here only are found
the gland-secretion and the " cellular "
secretion. In the cotyledonary parts the
glands are absent. Here the villi are
formed, and they effect an attachment to
the mucosa by the greater activity of the
trophoblast. Assheton has suggested that
this hyper-activity may be stimulated by
the absence of glands and consequently of
uterine milk in the cotyledons, the foetal
ectoderm attacking the mucous membrane
more vigorously in order to obtain food.
The blood effusions are also cotyledonary,
and the eosin and iron reactions are
obtainable in the adjacent trophoblast,
and not at other places. Finally, it is
probable that the exchange of oxygen
and carbonic dioxide is carried out in
the cotyledons. Here the maternal capillaries are more dilated
than outside the burrs, and they come close up to the surface,
some of them even impinging on the lining membrane of the
crypts. Between them and the allantoic vessels in the villi inter-
vene only a small amount of mesoblast, the cellular trophoblast, and
the lining of the crypts which, according to Assheton, corresponds
to the plasmodiblast of the bat. In the inter-cotyledonary regions,
on the other hand, the foetal vessels are related to the orifices of the
glands, and appear to be concerned principally with the absorption of
their secretion. As already mentioned, the villi may also be concerned
with the excretion of waste products of haemoglobin.

Bonnet was the first to show that the trophoblast in Ruminants
was actively phagocytic and absorbed the constituents of the uterine
milk (Fig. 120). He demonstrated the presence of fat globules,
haemoglobin and its derivatives, degenerated leucocytes and "Stabchen "
(Fig. 121) — in short, all the histologically demonstrable constituents

FIG. 120. — Ingestion and dis-
integration of red blood
corpuscles by the tropho-
blast of the sheep. (From
Jenkinson's " Notes on the
Histology and Physiology
of the Placenta in Ungu-
lata," Proc. Zool. Soc,., Lon-
don, vol. i., 1906.)

440 THE PHYSIOLOGY OF REPRODUCTION

«

of the embryotrophe — in the trophoblast. Many, if not all, of the
cellular elements are partially degenerated before absorption. The
appearances suggest an enzyme action on the part of the trophoblast.
and perhaps also the leucocytes, but no proteolytic or lipolytic enzyme
is contained in glycerin extracts of the maternal or foetal part of the
cotyledon.

After their absorption, the disintegration of the cellular constit-
uents is completed in the trophoblast, and they are no longer
recognisable as individual elements. Their products are transmitted
to the foetal vessels, though they may first be elaborated in the
trophoblast into a form or forms suitable for the use of the embryo
in the development of its various organs.

LEMUROIDEA. — Many of the lemurs have a simple avillous diffuse
placenta, as Turner l first pointed out in specimens from Madagascar.
Hubrecht has investigated two others found in the East Indies —
Tarsiusz and Nydicebus? The latter has also a diffuse placenta.
Yilli develop over the whole of the chorion, and fit into vascular
crypts in the uterine mucosa from which they are easily retracted at
birth. The epithelium of the crypts .persists as in the cow, and the
" osmotic interchange takes place through two cell-layers of different
origin, and of different physiological significance (phylogenetically).
Tarsius approaches more closely to the Insectivora and Primates.
The trophoblast proliferates and penetrates into the mucosa, and
maternal blood circulates in its spaces. The mesoblast grows
profusely, and forms with the trophoblast a true chorion in Hubrecht's
restricted sense. The placenta is discoid. In Galacjo agisi/mbanns,
Strahl 4 has shown that a layer of secretion lies between the uterus
and the ovum from the beginning of pregnancy. It is absorbed by
the ectoderm, the cells of which are vesiculated over the gland orifices.
Many blood extravasations occur in the connective tissue of the
mucosa, and the red blood corpuscles undergo changes as in the sheep,
the glandular cells and embryotrophe containing granules which give
an iron reaction. At the extremity of each chorionic villus is a slight
pit the cells surrounding which contain a granular greenish substance
derived presumably from hiemoglobin. Turner 5 had previously noted
in lemurs the intense brown staining of the glands from effused
blood.

1 Turner, "On the Placentation of the Lemurs," Phil. Trans. Roy. <S'oc.,
London, vol. clxvi., 1876.

2 Hubrecht, " Ueber die Entwicklung des Placenta von Tarsius, etc.," Internal.
Congr. of Zool., Cambridge, 1898.

:* Hubrecht, "Spolia Nemoris," Quar. Jour. Micr. Science, vol. xxxvi., 1895.

4 Strahl, " Die Verarbeitung von Blutextravasaten durch Uterindriisen,"
Anat. Anzeig., vol. xvi., 1899.

r> Turner, "The Placentation of Lemurs," ./o>n: of Aixit. <in<l /'/>//.<., vol. xii.,
1878.

FOETAL NUTRITION: THE PLACENTA

441

Jenkinsoii1 has lately investigated the placenta in a species of
Lepilemur and found that it conforms in structure to those of other
members of the Lemuroidea excepting Tarsius. " In the Lemuroid

3

>>

s

placenta the relation between foetal and maternal circulations is
brought about by the production of vascular trophoblastic villi, which
fit into crypts lined by a persistent uterine epithelium. So the
placenta, therefore, resembles that of an ungulate: it is of the so-
called ' Indeciduate ' type. The allantois is large and occupies a great

1 Jenkinson, " The Placenta of the Lemur," Quar. Jour. Micr. Science, vol. Ixi.,
1915.

442 THE PHYSIOLOGY OF REPRODUCTION

deal, if not the whole, of the space between the amnion and the
chorion."

CETACEA. — There is a diffuse indeciduate placenta in Orca, uniformly
studded with branched villi which are absent only at the ends of the
chorionic sac, that is, opposite the os uteri and the Fallopian tubes.
The sac extends into both cornua.

SIREXIA. — The placenta in Halicore is diffuse, indeciduate, and
zonary (see above, p. 408). The uterine epithelium persists in the
crypts. " Stabchen " or hippomanes (see p. 437) have been found.

EDENTATA. — The placenta is said to be zonary and deciduate in
Orycteropus (unlike most Edentates), bell-shaped in Myrmecophaga
and Tamandua, poly-cotyledonary in Bradypus, oval in Dasypus, and
diffuse in Manis and Cholcepus.1 The details of placental development
have not been worked out in any of these animals and the constitution
of the embryotrophe is unknown.

IV. THE PLACENTA IN DECIDUATA

In the Deciduata three modes of attachment between embryo and
mother are found : Centric, in which the blastocyst rests in the cavity
of the uterus, attains a large size, and comes in contact with the \vall
over its whole circumference ; Excentric, in which the blastocyst remains
small and lodges in a furrow of the uterine mucosa, and later a
decidua reflexa is formed ; Interstitial, in which the small blastocyst
attacks the mucosa at one point and reaches the connective tissue.
In this form also a decidua reflexa is formed.

In the neighbourhood of the attachment the mucosa degenerates,
but the connective tissue cells usually enlarge to form decidual cells
before degeneration sets in.2 The capillaries dilate and come in
contact with the trophoblast. The mucosa interlocks so closely with
the total villi that the two tissues cannot be separated without injury.

CARNIVORA.— The Carnivora are characterised by a zonary form
of deciduate placenta. The following account of its development
refers particularly to the dog and cat, which have been most
frequently investigated. The gestation period in the cat is on ah
average sixty days, and in the dog fifty-eight to sixty-three days. In
both the ovum takes a comparatively long time to traverse the
oviduct. On reaching the uterus the blastocyst is covered by a thick
prochorion which prevents adhesion for a considerable period.

The mucosa is matured, as in Ungulates, at the first procestruin
by the development of a well-differentiated sub-epithelial cellular
layer, and of the glands and crypts (see p. 430). The crypts provide

1 Jenkinson, Vertebrate Embryology, Oxford, 1913.
'- But see p. 457.

FCETAL NUTRITION: THE PLACENTA

443

an increase of superficies and of secreting epithelium, and are later
concerned in the attachment of the ovum. They have been recognised

Sp

FIG. 122. — The uterine mucosa of the dog about the twenty-third day of
pregnancy. (From Duval's " Le Placenta des Carnassiers," Jour. (b>
UAnat. et de la Phys., 1893.)

mes, Mesoblast ; tr, trophoblast ; <\ capillary layer ; e?, layer of glandular
detritus ; g, glands' of compact layer ; ftp, dilated glands of spongy layer.

by all the authorities with the exception of Robinson,1 who states that
he can find no evidence that any of the crypts are other than the ducts
of the uterine glands. At the first and each succeeding prooestrum
there is a marked hypenemia of the mucosa, and from the rupture of

1 Robinson, Hunterian Lectures, Jour, of Anat. and Phys., vol. xxxviii., 1904.

444 THE PHYSIOLOGY OF REPRODUCTION

some of the superficial capillaries miliary haemorrhages occur (see
Chapter ILL).

At the beginning of pregnancy, blood effusions are found close
under the surface of the mucous membrane, but bleeding into the
uterine cavity, which took place during the procestrum, has entirely
ceased. The epithelium of the surface glands and crypts is swollen
and pervaded with minute fat globules in the dog (Bonnet x) and cat
(Melissenos 2). The glands widen quickly into "chambers," and
tracts of their proliferated epithelium are invaginated, and often
obliterate the lumen. The widening of the glands and crypts makes
the deep layer spongy. The capillaries increase and form practically
the whole of the sub-epithelial layer. Immediately below it lies the
layer of glandular ducts which are obliterated by debris resulting from
the degeneration of the proliferated epithelial cells. Between it and
the spongy layer is the compact layer, also formed from the sub-
epithelial layer. In it the glands are not so widely dilated and the
connective tissue is more abundant (Fig. 122).

The embryotrophe at this stage differs from that in Ungulates.
The glandular secretion is less fluid, perhaps because the lymph
transudate is less abundant (Kolster3). It surrounds the ovum to
form the prochorion or " Gallertschicht," and is, according to Bonnet,4
absorbed by the trophoblast.

When the prochoriou disappears, the foetal ectoderm already has
proliferated over a broad zone of the citron-shaped ovum (Fig. 123),
to form villosities which attack the surface of the mucosa, and obtain
an attachment to it — about the twentieth day in the dog (Duval 5)
and the twelfth day in the cat (Robinson). Vascular processes of the
allantois grow into the centre of the trophoblastic villi, first 'over a
limited discoid area, and later over the whole zone as the allantois
spreads round the wall. Hence the rudimentary placenta is discoid
and the completed placenta zonary.

In procuring attachment to the uterus many of the villi project
into glands and crypts. According to Strahl,6 the epithelium lining
the ducts and the surface of the uterine cavity is then transformed
into a syncytiurn and invests the villi externally. Heinricius 7 is of

1 Bonnet, "Beitrage zur Embryologie des Hundes," Anat. Jfefte, vol. xx., 1902.

2 Melissenos, " Ueber die Fettkbrnchen und ihre Bedeutung in der Placenta
bei den Nagern und der Katze," Arch. f. mikr. Anat., vol. Ixvii., 1906.

3 Kolster, " Ueber die Zusammensetzung der Embryotrophe der Wirbel-
thiere," Ergebn. d. Anat., vol. xvi., 1906.

4 Bonnet, "Ueber das 'Prochorion' des Hundekeimblase," Anat. Anzeig., vol.
xiii., 1897.

5 Duval, "Le Placenta des Carnassiers," Jour, de I' Anat. et de la Phys., 1893.

6 Strahl, " Die histologischen Veranderungen d. Uterusepithel. in d. Raub-
thierplacenta," Arch. f. Anat. u. Phys., Supplement, 1890.

7 Heinricius, " Ueber die Entwicklung und Struktur der Placenta beim
Hunde," Arch. f. mikr. Anat., vol. xxxiii., 1889.

FCETAL NUTRITION: THE PLACENTA 445

opinion that the epithelium disappears, and the syncytium is formed
by the uterine connective tissue. But it is now generally recognised
that the syncytium is trophoblastic. It has been proved by Strahl
himself, and by Duval, that many of the villi obtain attachment at
parts of the surface where there are no gland openings or crypts,
and penetrate into the substance of the rnucosa. Before the dis-
appearance of the epithelium, the cells lose their outlines and form
a homogeneous mass of protoplasm with fragmented nuclei. This
degenerated tissue ought not, as Bonnet l emphasised, to be known
as syncytium, which represents an active protoplasmic condition (see
p. 398). The name which he suggested, symplasma, is very con-
venient and is used here. It is not only the surface epithelium
which forms a symplasma. The glandular epithelium, the connective
tissue cells, and extravasated blood may also give rise to a symplasma

FIG. 123. — Ovum with zonary band of villi. (From Hertwig's Entwicklungs-
geschichte des Menschen und der Wirbelthiere, by permission of Gustav
Fischer.)

which may be designated glandular, connective tissue, and hcematogenous
respectively. All are formed to a large extent in the placenta of
Carnivores, and their resemblance to the trophoblastic syncytium
has led to much confusion.

After the destruction of the epithelium, the villi penetrate into
the deeper tissues of the mucosa by gradually absorbing the sym-
plasmata, and branch to form secondary and tertiary villi. When
the ectoderm reaches the capillary layer, it sends out protoplasmic
processes which encircle the dilated vessels. The trophoblast on
the sides of the villi becomes syncytial, but retains its cellular
character at the tips. Internally the villi contain vascular cores of
mesoblast. Hence is formed the angioplasmode of Duval — a con-
tinuous layer of foetal vascular villi, clad with syncytium, penetrating
everywhere into the capillary layer, and leading to a disappearance of
all the maternal tissues except the vessels (Fig. 124). By the
.epithelial arcades at the tips, the layer of villi rests on the sheet

1 Bonnet, " Ueber Syncytien, Plasmodien und Symplasma, etc.," Monatsschr.
f. Oeburtsh. u. Gynak., vol. xviii., 1903.

446

THE PHYSIOLOGY OF REPRODUCTION

of glandular detritus and the compact layer, which in turn form a
symplasma and undergo absorption. Thus the foatal structures reach
the spongy layer, in which the glandular culs-de-sac have expanded
to form large cavities separated by partitions, the mesenteriform

FIG. 124. — The angioplasmode of the dog at the thirtieth day of pregnancy.
(From Duval's " Le Placenta des Carnassiers," Jouni. d<> FAnat. et de la
Phys., 1893.)

ms, Mesoblast ; lr, trophoblast ; ae, ectodermic arcades ; d, layer of
glandular detritus.

lamella?. Gradually the roof of this layer is also absorbed by the
trophoblast, and the ectodermal arcades at the tips of the villi gain
a permanent attachment to the mesenteriform lamella^. At the same
time, by the further branching and penetration of the foetal nieso-
derm in the angioplasmode, the tissue is broken up into a series of
labyrinthine lamellae, which consist of a network of maternal vessels
clothed on each side by syncytial trophoblast. The meshes of the

FCETAL NUTRITION: THE PLACENTA

447

network are penetrated by the vessels of the villi. In this way,
according to Duval, the labyrinth is formed. In it the maternal and
the foetal blood are separated by the endothelium of the uterine
capillaries, a cellular layer (considered foetal by Duval and maternal
by Heinricius) which later disappears, the syncytiurn, mesoblast, and
foetal capillary walls.

At places, however, the villi come directly in contact with
maternal blood, especially at the "green border" of the placenta,

nvm_ T ^^

JU% A -J"*3j^^^ta^%
.j;../ >Ar» l&Z^ -

J^f.---'-:?™^.:-*^

*2zf'^ ^aa_

^•^^f- %^3^^^^p^1
•-^•--^ ~^-~ — • — — -o^i— . , „ .>
r~^>*"'" .s-^.L- _ _

ff*.~

^ ^—— <=i£Z!Z<- — ^•^Z^T.'.t!^'' - 'tJa

'""^.A-v.^.r^VNA.^-- ^/-.^«WVrL~.--- ., ^J-o"?

•««x~«»o»0«»o0^^>M0.J:fc>-^>'^<> 0°°

FIG. 125. — The labyrinth and the green border of the placenta of the dog at
the fortieth day of pregnancy. To the right are two lobules of the
angioplasmode which have reached the stage of complexity of the
labyrinthine lamellse : to the left is the green border, the cavities of
which, normally filled with blood, are indicated by a cross. (From Duval's
" Le Placenta des Carnassiers," Jour, de VAnat. et de la Phys., 1893.)

1, 2, and 3, Basal lamellae of the green border ; 4, basal lamella of lobule

of labyrinth.

V

which forms a characteristic appearance in some of the Carnivora.
In all the members of the order, larger or smaller maternal
haemorrhages occur at an early period after the attachment of the
blastodermic vesicle. The effusions vary in size and position. In
the dog they occur regularly along the margins of the placental zone,
and form the bordure verte; in addition smaller haemorrhages !•£•
place into the substance of the placenta, and form the "green
pockets," which may be isolated or joined to the green border by
bridges (Fig. 125). In the cat the haemorrhages occur in irregular
positions and do not assume the green colour typical of the dog.
Indications of a green border are present in the earlier stages, but

448 THE PHYSIOLOGY OF REPRODUCTION

not in the completed placenta. In the otter and badger the effusion
takes the form of a large blood-pouch, filled with a great variety of
blood derivatives. In the ferret the conditions are similar ; the main
effusion occurs at the anti-mesometrial border of the uterus, and
divides the zone into two lateral discs. According to Robinson, it
lifts the trophoblast from the decidua, and forces it in the form of
irregular pouches towards the interior of the ovum. Strahl and
Bonnet also state that the blood is effused between the mucosa and
the blastodermic vesicle, and thus is contained in spaces whose walls
are maternal on the one side and foetal on the other. According to
Duval the blood-spaces are entirely lined by trophoblast, and with
the advance of the villi other and larger haemorrhages occur,
coalescing to form the green border and islands. In either case the
trophoblast is in direct contact with maternal blood. There the wall
of the blastodermic vesicle is avillous but strongly folded, the ends of
the ectodermal cells are expanded like clubs, and their protoplasm
becomes coarsely reticular. Into the meshes the constituents of the
green pulpy mass, unaltered erythrocytes and haemoglobin or its
derivatives, are absorbed by phagocytosis.

From the preceding account, it is clear that certain resemblances
and certain differences exist between Carnivora and Ungulata in the
composition of the embryotrophe. The most notable difference hi
the zonary placenta is the absence of the large amount of milky fluid
which arises in the sheep from the glandular secretion and the
transudation of lymph. In Carnivora the gland secretion is less
important. Though the deep parts of the glands which lie in the
glandular layer may secrete, the epithelium of the more superficial
parts proliferates, and then degenerates and loses its secretory
function ; finally it forms a symplasma which plugs up the lumen
of the glands.

On the other hand, the amount of nutriment furnished directly
from the maternal blood is increased. It is found in the extravasa-
tions already described, and as individual blood corpuscles and
droplets of haemoglobin or its derivatives in the lumina of glands.
Leucocytes are found during the whole of pregnancy, but in less
abundance than in the sheep. They do not act to the same extent as
store-houses of fat, but some of them, the siderophores, contain
granules which give an iron reaction. In the course of pregnancy
they disappear comparatively early, with the exception of a few in
the deep glandular layer. Fat is found in the intact epithelium
of the glands, and in the lumen after desquamation of the cells. It
appears in the epithelium partly as an infiltration and partly as a
degeneration product of the protoplasm.

In the Carnivora the foetal ectoderm of the zonular band of

FCETAL NUTRITION: THE PLACENTA 449

attachment attacks the uterine mucosa more strongly than in the
Ungulata. As a result, the maternal tissues, with the exception of
the septa containing the placental vessels, disappear down to the
middle of the spongy layer, and the tissue which is destroyed serves
as pabulum for the developing embryo. Van der Brock1 suggests
that the general oedema of the uterine mucosa may lead, as elsewhere,
to its malnutrition and degeneration, and thus it may fall an easy
prey to the trophoblast. Others maintain that the degeneration is
brought about by a trophoblastic influence, perhaps of the nature of
an enzyme action. The result is a transformation of all the elements
to a symplasma. In the cat the connective tissue cells may form
large decidual cells before their final destruction.

As in the Indeciduates, there is strong histological evidence
that the trophoblast is actively phagocytic, and takes up, as it meets
them, the constituents of the prochorion, and later the degenerated
tissues and extra vasated blood. In the neighbourhood of the
extravasations active absorption is indicated by the change in shape
of the trophoblast cells and by their pigmentation. In the mesoblast
of the villi and its vessels no trace is found of any of the formed
elements of the embryotrophe, a proof that they undergo further
transformation in the trophoblast after absorption.

The interchange of oxygen and carbonic dioxide apparently
occurs in the labyrinth, as in the cotyledons of the sheep. Here only
is the foetal circulation brought into close proximity with circulating
maternal blood. Other foetal waste products are probably also got
rid of in the labyrinth. Nolf 2 suggests that the excretory products
may be responsible for the degeneration of the maternal tissues into
a symplasma.

In how far the other substances necessary for the growth of the
embryo are taken up respectively from the circulating blood by
purely physical or physiologically selective processes, and from the
extravasated blood effusions by direct phagocytosis, is not known.3

1 Van der Brock, " Die Eihiillen und die Placenta von Phoca, vitidiim"
Petnis Camper, D. ii. Quoted by Kolster (Ergebn. d. Anat., vol. xvi., 1906).

2 Nolf, "Etude des modifications de la muqueuse uterine pendant la gestation
chez le murin," Arch, de Biol., vol. xiv., 1896.

3 Cunningham has investigated the fluid and salt interchanges between
mother and foetus in cats in the later stages of pregnancy. He injected into the
venous system balanced solutions of potassium ferrocyanide and iron ammonium
citrate, salts which can be precipitated as Prussian blue, and consequently
can be readily followed along the route traversed to their ultimate location.
It was found that both maternal and foetal endothelia were easily permeable
to the two salts, but foetal ectoderm reacted differently in terms both of
permeability and length of time required. In experiments of short duration
no trace of either salt was found in the amniotic fluid, foetal urine, or tissue
extract. In those of longer duration sodium ferrocyanide was found in the
amniotic fluid and foetal urine, but no trace of iron ammonium citrate was ever
detected in any foetal tissues. The placenta in the shorter experiments showed

15

450 THE PHYSIOLOGY OF REPRODUCTION

It has been shown that the foetal fat in the dog is not necessarily
derived directly from fat fed to the mother, for Thiemich 1 fed a dog
on widely different fats (palmitin and linseed oil, etc.) during t\\<>
successive pregnancies but found the fat in the foetus to be the same
in each case (see below, p. 54o).

•

PROBO.SCIDEA. — In the elephant, the allantois is large and

vesicular. Short villi are developed over a large area of the
blastodermic vesicle. They lodge in pre-existing depressions in the
uterine wall, but the trophoblast is inactive and does not attack
the maternal tissues (Assheton2). Over a zonary area, however, the
villi are much longer, and, penetrating deeply into the maternal
tissiies, they form a large mass of tissue in the meshes of which
maternal blood circulates. Hence the zonary placenta differs from
that of Carnivores and resembles that of Insectivores, in which,
however, the maternal blood circulates in trophoblastic spaces before
the advent of foetal capillaries.

Though no red blood corpuscles appear to be absorbed as such
by the trophoblast, there is evidence of an active absorption of
haemoglobin derivatives, the presence of iron compounds being easily
demonstrated, especially in the cores of the villi and the walls of
the foetal capillaries. In the syncytial trophoblast, however, the
Prussian-blue test is negative (see p. 511).

At birth the long villi are left in situ and absorbed by the
maternal tissues.

HYKAX. — As in the elephant, the placenta of Hyrax has been
studied only in isolated specimens, and its development is not known.
According to Assheton,3 the trophoblast is probably thickened all
round the wall of the blastocyst, as in the hedgehog and man, but
there is no appearance of a decidua reflexa. Maternal blood is
carried directly to the foetal side of the trophoblast, where it is
close to the foetal vessels, and so may provide nutriment. It
then trickles back through a complicated system of lacuna- in the
trophoblast.

The placenta is at first diffuse and later zonary. In the mucosa

Prussian blue in the maternal endothelium, but none within the ectoderm.
In the longer experiments blue granules had penetrated the ectodermal layer,
but not the ftetal endothelium. The placental ectoderm thus shows a marked
selective behaviour. (Cunningham, R. G., "Studies in Placental Permeability —
I. The Differential Resistance to Certain Solutions Offered by the Placenta in
the Cat," Amcr. Jour, of Pkysiol., vol. liii., 1920.) See also below, p. 466, footnote.

1 Thiemich, " Uber die Herkunft des Fotalen Fettes," Zent. f. Phys., vol. xii.,
1898.

2 Assheton, " The Morphology of the Ungulate Placenta, with Remarks on
the Elephant and Hyrax" Phil. Tram. Roy. *S'oc., London, Ser. B., vol. cxcviii.,
1906.

3 Assheton, loc. cit.

FCETAL NUTRITION: THE PLACENTA 451

of the placental area the glands disappear early, and a great increase
in the interglandular stroma occurs, as in Rodents.1

RODENTIA. — Among the Rodents there are variations in the mode
of attachment. It is centric in the rabbit, excentric in the mouse
and rat, and interstitial in the guinea-pig. In all the ultimate form
of the placenta is discoid.

It was in Rodents that the proliferation and vascularisation of
the trophoblast were first described by Selenka.2 Later Duval3
gave a fuller account of the earlier stages, and Hubrecht dis-
covered the same conditions in other
orders.

Rabbit. — The fertilised ovum of
the rabbit, clothed by the prochorion,
reaches the uterus at the beginning
of the fourth day after coitus. At
first it has no fixed position ; but by
the seventh day, when the blastocyst
is about five millimetres in diameter,
the prochorion lies so closely on the
surface of the uterus that it fixes
the ovum. At the end of the eighth
day the prochorion ruptures, and
the blastodermic vesicle probably
collapses at the same time by injury
to its wall.4

The " mature " uterine mucous
membrane of the non-pregnant
rabbit already shows specialised

FIG. 126. — Transverse section of a
four days' gestation sac of the
rabbit. The mucosa is differ-
entiated into six definite folds.
The two folds nearest the
mesometrium are the largest
and mark the site of placental
attachment. (From Chipman's
" The Placenta of the Rabbit,"
Labor. Rep., Roy. Coll. Phys.,
Edinburgh, vol. viii., 1903.)

p, p', Placental folds ; n, n',
peri-placental folds ; o, o, ol>-
placental folds.

structures, which are of importance
for the attachment and nutrition of a future embryo. These consist
of symmetrical pairs of longitudinal folds, first described by Hollard,5
and subsequently named by Minot : 6 placental folds, the largest,

1 Hubrecht (IJuar. Jour. Micr. Science, 1908) draws attention to the peculiar
position of Hyrax. It has many archaic peculiarities, and has been placed
near Rodents, elephants, and Ungulates by different autliors. Yet its placental
characters resemble those of the hedgehog and man. This he takes as strong
evidence that the type of placenta found in Hyrax, the hedgehog, and man
diverges less widely from the primitive type than the placenta of Ungulates
and Rodents.

- Selenka, Keimblatter und Primitivorgane der Maus, 1883.

3 Duval, " Le Placenta des Rongeurs," Jour, de I'Anat. et de la Phys., 1889-92.

4 See Hertwig's Kntwicklwngsgeschichte des Menschen und der Wirbelthiere,
1906.

6 Hollard, "Recherche sur le Placenta des Rongeurs," Annales des Sciences
Naturdles, 1863.

6 Minot, "Die Placenta des Kaninchens," Diol. Centralbl., vol. x., 1890.

452 THE. PHYSIOLOGY OF REPRODUCTION

situated one on each side of the groove corresponding to the insertion
of the mesometrium ; ob-placental folds, the smallest, opposite the
mesometrium ; peri-placental folds, intermediate in position and size
(Fig. 126). Each fold is divided by transverse fissures into rectangular
areas, the coussinets of Hollard. At the onset of pregnancy two of
these areas on the placental folds, placed one on either side of the
mesometrial groove, hypertrophy and form the maternal part of the
future discoid placenta (Bischoff1), which is thus bi-lobed (Fig. 127).
The folds of the mucosa are essentially increased areas of the nmcosal
connective tissue, but they differ from the cotyledons of Ruminants

in having glands.

On the entrance of a fertilised
ovum into the uterus, the folds,
especially the ob-placental, become
shortened, and a localised actual
cavity appears which is occupied
by the blastocyst. At the same
time there is a marked hyperplasia
of the cellular connective tissue of
the placental and peri-placental
folds, leading to a thickening of
their bases (Chipman2). By the
sixth day the capillaries are also
increased in these regions. In the
ob-placental folds appear enormous
giant-cells, derived by a process of
" degenerative hypertrophy " from
the epithelium of the surface and
glands.3 They persist till at least
mid-pregnancy, and are probably

absorbed by the trophoblast overlying the yolk-sac: In the placental
lobes the epithelial cells proliferate and fill up the superficial culs-de-
sac of the mucous membrane. The glands are as yet unchanged, and
the increased blood supply leads to a free secretion which is usually
considered to be added to the albumen -layer, and then to be absorbed
by the trophoblast. There is no appreciable transudation of lymph
such as occurs in Ruminants.

1 Bischoff, Entwickelung des Kaninchen-Eies, Braunschweig, 1842.

2 Chipman, " Observations on the Placenta of the Rabbit, with Special
Reference to the Presence of Glycogen, Fat, and Iron," Lab. Rep., Roy.
Coll. Phys., Edinburgh, vol. viii., 1903. The development of the placenta is
carefully traced in a complete age-series of pregnant rabbits and admirably
figured by many photo-micrographs. The account as given here is based
mainly on Chipman's monograph, but the phraseology is sometimes changed.

3 Mr Hammond suggests that these may be detached cells from the tropho-

FIG 127. — Transverse section of a
seven days' gestation sac of the
rabbit (Chipman). The placental
folds (coussinets) are large (a) :
the muscular walls of the sac
are thin.

blast. Cf. Hammond, "On the Causes Responsible for the Developmental Progress
of the Mammary Glands in the Rabbit," Proc. Roy. Soc., B., vol.

Ixxxix., 1917.

FCETAL NUTRITION: THE PLACENTA

453

*•"*

As the blastodermic vesicle grows, it presses against the folds and

levels them. Hence at the tune of attachment the surfaces of the

placental lobes are nearly regular. The covering epithelium again

returns to normal, but

the active proliferation

of the connective tissue

cells is continued to "X

form the placental coty-
ledons. At the same

time the trophoblast

proliferates in concentric r.

areas on either side of

the embryonic rudiment,

which is placed opposite

the groove between the

placental cushions. Here

the ovum is generally
said to gain its first
attachment, the ob-
placental lobes having by
this time disappeared.1

Where the maternal
and fretal tissues are in
contact, the surface
epithelium shows a form
of degeneration similar
to the epithelial sym-
plasma of the zonary
placenta — fusion of cells
and fragmentation of
nuclei. It is attacked
by the thickened, horse-
shoe-shaped trophoblast,
the ectoplacenta of Duval,
and its edge presents
microscopically a " bitten
or corroded appearance."
This phagocytic or
chemical action leads
later to the complete disappearance of the epithelium, so that
the trophoblast comes in contact with the connective tissue of

1 Assheton (Quar. Jour. Micr. Science, vol. xxxvii., 1895) states that the tropho-
blast shows papillary thickenings over the ob-placental and peri-placental
obes, and that by them the ovum obtains the first attachment over its lower
pole.

FIG. 128. — Section through uterine mucosa of
rabbit pregnant about eighteen days. The
section shows decidual tissue and, "near the
surface, giant-cells which are supposed to
be detached trophoblast cells, and therefore
of foetal origin. (From Hammond.)

454 THE PHYSIOLOGY OF REPRODUCTION

the uterus. The glands are dilated, and their proliferated endo-
thelium forms a symplasma which blocks the lumina. At these
places the trophoblast advances more quickly, as if the resist-
ance was weaker, and the line of attachment is undulating
(Fig. 129). The dips thus correspond to the gland orifices and
represent the beginnings of the future villi. The blood-vessels are
large and numerous and have no adventitia, i.e. they are wholly
capillaries. But the more deeply placed of them acquire an
adventitia, the perivascular sheath (Masquelin and Swaen1). It is

FIG. 129. — Thickened ectoderm (ectoplacenta) in the rabbit, attached to
placental lobe and dipping more deeply at the position of the glands.
(Chipman.)

<?c, Foetal ectoderm ; /, line of attachment of ectoderm ; rf, foetal ectoderm
dipping into placental gland ; gr, terminal cul-de-sac of placental gland.

formed of one or two layers of large connective tissue cells which
represent the first appearance of the decidual cells. After the
destruction of the superficial and glandular epithelium, the tropho-
blast advances into the interglandular tissue, the cells of which
degenerate in turn and are absorbed. The advance is most rapid
where a capillary is met with.

The mucous membrane is now differentiated into two zones, the
intermediary region and the region of the uterine sinuses (Duval).
The intermediary region lies superficially. It is closely packed with
fusiform stroina cells and capillaries with thin perivascular sheaths

1 Masquelin and Swaen, " Developpement du placenta maternel chez le lapin,"
Bull, de VAcad. Roy. de Belg., 1879.

FCETAL NUTRITION: THE PLACENTA 455

of unimicleate decidual cells. "It suggests a reaction of 'the maternal
placenta to the 'parasitic' foatal placenta" (Chipman ; see also p. 403).
By the influence of the trophoblast the decidual cells increase in size
and become multinucleate (Maximow 1). They lose their perivascular
position and pervade the whole of the region. In their formation all
traces of the gland ducts are lost, the cells of the latter appearing to
serve as pabulum for the decidual cells. In the region of the uterine
sinuses the blood-vessels dilate to form large spaces, and the decidual
cells remain uninucleate till a considerably later period. The junction
between the two zones is marked by the blind ends of the glands,
which are filled with degenerated epithelium. In section each appears
as an island of glandular symplasma.

At the tenth day the allantois joins the outer wall of the blasto-
cyst over the site of the future placenta. The trophoblast of this
region is differentiated into two layers, the plasmodiblast and the
underlying cytoblast. The latter disappears before the end of
pregnancy. Processes of vascular mesoblast invade the trophoblast
at intervals, and break it up into columns. At the same time the
foetal tissues continue to advance and surround maternal capillaries,
the eiidothelium of which they replace. In the zonary placenta of
Carnivora the trophoblast surrounds the vessels without destroying
the endothelium. In the rabbit the ectodermal processes are hollow
tubes which surround the vessels ; they are closed on the fo3tal side
and open on the maternal side. Their cavity is filled with maternal
blood, and externally lies the cytoblast and vascular mesoblast.
Such are the " villi." Subsequently the arrangement becomes more
complex, each hollow column being divided up into a series of hollow
tubes parallel to the original column, and each tube in turn forming
a series of hollow tubules. At each division the thickness of fo?tal
tissue between the maternal blood in the axis and the foetal vessels
decreases, till finally there is only a film of trophoblast and the
vascular wall. At places the trophoblast even is wanting, and the
foetal endothelium alone intervenes between the two blood-streams.

The endothelium of the maternal capillaries frequently ruptures
just before it is overtaken by the ectoderm, and irregular blood
extravasations are formed, and later surrounded by trophoblast. In
the deeper layers of the intermediary region, according to Chipman,
capillary haemorrhages occur more slowly, and give rise to a fibrinous
tissue with red and white blood corpuscles scattered through it.
This is similar to the Imematogenous symplasma of Bonnet. It
gradually increases in amount, and extends to the region of the
uterine sinuses.

1 Maximow, "Zur Kenntnis des feineren Baues der Kaninchen-Plaeenta,"
Ai-ch.f. mik-r. Anat., vol. li., 1897. See also ibid., vol. Ivi., 1900.

456 THE PHYSIOLOGY OF REPRODUCTION

While the foetal ectoderm advances along the vessels, it remains
stationary at the non-vascular parts. Hence there is an interlocking
of maternal and foetal tissues, and peninsulse of multinucleate cells
come to lie between the projections of the trophoblast. At the same
time the intermediary region decreases in thickness, and the ecto-
derm reaches the superficial sinuses of the deeper zone. Here the
uninucleate decidual cells again become multinucleate, apparently
at the expense of the blood symplasma, in the same manner as
formerly at the expense of the glandular symplasma. The sinuses
enlarge, and their walls proliferate into several layers of degenerated
cells, which after mid-term are gradually replaced by laminae of
fibrin.

At a later period the intermediary zone still further decreases in
thickness, and the multinucleate cells gradually "melt to form a
granular detritus " (Duval). At the end of pregnancy the maternal
placenta consists almost entirely of blood and blood symplasma,
except for a thin rim of tissue containing blood-sinuses at the zone
of separation. The gestation period is thirty days.

As compared with the placenta of Carnivora, it is obvious that
the dilatation of maternal vessels is much more marked in the
rabbit, and throughout the placenta the maternal blood is in direct
contact with the trophoblast, and not only at the border or round
a blood-pouch. The blood is not degenerated to a sufficient extent
to exhibit the varieties of pigmentation found in the zonary placenta.
Chipman does not state whether the maternal blood circulates in the
trophoblastic tubes, but Maximow l says that it does. Similarly
Duval says : " The maternal blood circulates from the foetal extremity
towards the maternal extremity of a lobule " (i.e. the series of tubules
derived from one tube). According to Masius,2 " the maternal blood
circulates in an ectoderrnal mass of foetal origin." Herein lies a great
difference between the placenta of Rodents and Carnivores or Ungu-
lates. In the sheep the main nutriment is furnished by the glands ;
the maternal blood which is in contact with foetal ectoderm is
stationary and small in amount, and serves chiefly as a supply of
iron ; the exchange of gases takes place through foetal and maternal
tissues. In the dog the gland secretion is less important ; the blood
is again stationary and restricted to certain situations, and it shows
markedly degenerative appearances, but it is greater in amount, and
probably furnishes other substances besides iron . for the foetus ; in
the angioplasmode the maternal blood circulates and here the exchange
of gases is effected, but again both maternal and foetal tissues inter-

1 Maximow, "Die ersten Entwicklungsstadien der Kaninchenplacenta," Arch,
f. mikr. Anat., vol. Ivi., 1900.

2 Masius, "De la Genese du Placenta chez le Lapin," Arch, de BioL, 1889.

FCETAL NUTRITION: THE PLACENTA 457

vene between the two blood-systems. In the rabbit the glandular
secretion is still less important after attachment, and even the blind
ends do not secrete; throughout the placenta there is normal
circulating maternal blood in direct contact with foetal tissues, and
it serves both as nutriment and for the exchange of gases. In
addition, there are stationary blood extravasations which are engulfed
by the trophoblast, but they are subsidiary. Both in the dog and
the rabbit there is a marked formation of symplasma which may be
connected, as Bonnet suggested for the dog and Maximow for the
rabbit, with the slowing of the circulation in the placenta, or may
be the result of a trophoblastic influence.

In the placenta of the rabbit there is one other difference which
marks it off from the placenta of Carnivores and links it with
Insectivores and man — the connective tissue cells of the mucosa
form decidual cells. They assist to an important degree in the pre-
paration of nutriment for the embryo. They exercise a phagocytic
action on the neighbouring degenerated maternal tissues, glandular
remnants and fibrin, and so attain their greatest development, while
at the same time they become store-houses of fostal nutriment. At
a later period they degenerate and are absorbed by the trophoblast.
Their possible function as a protection against the attack of the foetal
ectoderm has already been mentioned. At the end of pregnancy
their defence is 110 longer required, as the trophoblast has also lost
its activity. The so-called " decidual cells " of the Carnivora are a
later and different formation.

Iron Metabolism

The decidual cells are concerned in the metabolism, of iron, fat,
and glycogen for the foetus. In the rabbit, as contrasted with
Ruminants, the ingestion of healthy or degenerated erythrocytes
probably does not occur. Though Maximow states that they are
" present in the plasmodium," they appear to be in the plasmodium
only as the isolated peninsula} of decidual cells are in it, i.c: they
lie in spaces surrounded by trophoblast. Whether haemoglobin as
such or its more immediate derivatives in the form of organic iron
compounds are absorbed has not been investigated, but Chipman
has shown that inorganic iron compounds are present, and their
distribution speaks for their absorption by the trophoblast. The
compounds appear as blue-black granules in sections stained with
a weak watery solution of hsematoxylin. At the fourteenth day they
are present in the foetal mesoblast, especially where it approaches
the decidua. They increase in size and number for a few days and
then diminish, but some are still seen at the end of pregnancy. A
few granules appear in the trophoblast between the sixteenth and
'5 A

458 THE PHYSIOLOGY OF REPRODUCTION

twentieth days (Fig. 130). From the sixteenth day they are also
found in an increasing number of the decidual cells which lie close
to the fetal placenta ; after the twenty-fourth day, when the cells
degenerate, the granules are no longer discrete, but there are irregular
blue-black patches up to the end of pregnancy.

Such isolated data cannot be accurately interpreted. The fact
that the deposits in the three tissues are always situated in apposition
to each other speaks for their absorption by the foetal tissues ; on the
other hand, a very small number of granules are present in the
trophoblast, and only for a few days. It is possible that organic
iron compounds, not shown by the hrematoxylin stain, are absorbed
and broken up, and later appear as granules in the mesoderm. Their
further course to the foatal liver, in which they are stored, has not
been traced. It is to be noted that the iron compounds are not only
derived from htemoglobin. They may also represent degeneration
products of the nucleoproteins.

Hubrecht l has suggested that erythrocytes may be manufactured
in the decidual cells, and their iron-containing granules may thus be
utilised (see p. 518).

Fat Metabolism

Regarding.- the presence of fat in the placenta of a rabbit, a few
observations have been made by Eden,2 Maximow, and Masius.
Chipman has investigated the subject in greater detail, but he draws
no conclusions from the histological data. In reality, the study of
fat in the placenta is rendered difficult by its occurrence both as an
infiltration and in the degeneration of cells.

Fat is found in the fo3tal viscera, liver, heart, and mid-gut, before
the allantoic circulation is established. At this time, the tenth day,
the vitelline circulation is at its height, and the fat probably reaches
the embryo by its vessels, as it is also found in the hypoblast of the
area vasculosa. It may be derived from the absorption by the
trophoblast of fat droplets contained in the giant-cells of the peri-
placental folds. As the vitelline circulation diminishes, the fat
disappears from the embryonic viscera, and does not reappear till
four or five days after the establishment of the allantoic circulation.
During this interval fat is present in the extra-placental wall of the
blastocyst, but it probably arises by a degeneration of its cellular
protoplasm.

In the fcetal placenta, fat is never found in the mesoblast or
capillary walls, but it occurs in the trophoblast, especially where it

1 Hubrecht, " Ueber die Entwicklung der Placenta von Tarsius und Tupaja,"
Internal. Congr. of ZooL, Cambridge, 1898.

2 Ede^ " The Occurrence of Nutritive Fat in the Human Placenta," J'roc.
Roy. Soc. London, vol. lx., 1896.

FCETAL NUTRITION: THE PLACENTA

459

is in contact with maternal blood or decidua. It increases from the
twelfth to the sixteenth day, then it decreases, and a week later
disappears altogether. In the maternal placenta fat first appears
in the decidual cells which are nearest the trophoblast. They show

9

A

lvi #

.a

—

FIG. 130. — Iron granules in the placenta of the rabbit at the eighteenth day
of pregnancy. (Chipman.)

a, Iron granules in mesoblast ; b, iron granules in multinucleate decidual
cells ; g, iron granules in ectodermal tubules.

no sign of degeneration at this time, and they probably secrete the
fat globules. After increasing for a few days, it diminishes with
the atrophy of the decidual cells, and finally appears as fatty debris.
Fat is also present in the proliferating endothelium, and later in the
fibrin lamime of the uterine sinuses.

In the new-born foetus the main store of fat is contained in the
subcutaneous tissue. It is remarkable that it does not appear in

460 THE PHYSIOLOGY OF REPRODUCTION

this situation till the greater part of the fat has disappeared from
the placenta. It is either transmitted to the foetus in a form
which does not reduce osmic acid, or formed in the foetus itself
from other substances.. At birth the foetal viscera, especially the
liver, have a considerable store of fat which increases during suckling.

Glycogen Metabolism

The presence of glycogen in the placenta of the rabbit was
discovered by Claude Bernard1 in 1859. He showed its increase
and subsequent decrease during pregnancy, and concluded from his
observations that the placenta carried out for the foetus, in the
first half of intra-uterine life, the glycogenic function subsequently
assumed by the foetal liver. Godet 2 described two areas of glycogen-
containing cells, one immediately underlying the foetal villi, the
other in the deeper part of the placenta. Maximow investigated
. these cells at different stages of pregnancy ; he found glycogen in
the decidual cells of the vascular sheaths at the eighth day, gradually
increasing in amount and playing an important part in the nourish-
ment of the trophoblast. In the later stages glycogen disappeared
and the decidual tissue was transformed into polygonal multinucleate
cells rich in fat. Chipman recorded detailed observations in a more
complete age-series from the eighth day to the end of gestation. He
showed that glycogen was always present in the maternal part of
the placenta, but never in the foetal. Occurring in the decidual cells
of both zones, it increased and reached a maximum between the
twelfth and sixteenth days3 (Fig. 131); then it steadily diminished,
and in the last week only a few granules \vere found scattered in the
conglomerate masses of decidual cells. At the zone of separation,
however, glycogen granules were still contained in decidual cells.
Chipman also examined the foetal liver. In it he found that glycogen
appeared at the twenty-second day, and increased rapidly and
steadily in amount till the end of pregnancy.

These results have for the. most part been corroborated by
chemical analyses carried out by the writer, working in collaboration
with Dr. W. Cramer.4 They determined quantitatively the glycogen
of the maternal placenta, foetal liver, and remainder of the foetal

1 Bernard, "Sur une nouvelle fonction du placenta," Comp. Rend. Acurf. >>'<•?'.,
Paris, 1859.

2 Godet, " Recherches sur la structure intime du placenta du lapin," Divert.
Inaug. a la Fac. de Med. de Berne, Neuveville, 1877.

3 It has been shown that the corpus luteum in the rabbit reaches its maximum
•about the same time. (See Hammond and Marshall, Proc. Hoy. Soc., B., vol.
Ixxxvii., 1914 ; and Hammond, Proc. Roy. Soc., B., vol. Ixxxix., 1917.)

4 Lochhead and Cramer, "The Glycogenic Changes in the Placenta and the
Foetus of the Pregnant Rabbit," Proc. Roy. Soc. London, B., vol. Ixxx., 1908.

FCETAL NUTRITION: THE PLACENTA

461

body in an age-series of pregnant rabbits from the fourteenth day
to the end of pregnancy. The maternal placenta was separated
mechanically from the foetal placenta, and each was investigated
separately. The maternal part includes the two glycogenic areas,

-ss

FIG. 134. — Glycogenic areas of the rabbit's placenta at the twelfth day of
pregnancy. (Chipman.)

fp, Fcetal placenta, containing no glycogen ; ?V, intermediary region ; n<,
region of uterine sinuses ; ss, uterine sinuses with peri vascular sheaths
of uninucleate cells rich in glycogen ; g, glycogen granules in multi-
nucleate cells ; m, muscular wall immediately above which, at a later
date, the zone of separation, containing glycogenic decidual cells, is
differentiated.

the region of the uterine sinuses and the zone of separation. The
foetal part includes the peninsula?, of decidual tissue which form the
intermediary zone; the glycogen contained in it belongs wholly to
these peninsulas and represents the fraction most intimately related
to the trophoblast. It may on that account be termed the prooyimal
glycogen, while that of the maternal part is the distal glycogen. On

the fourteenth day the distal glycogen forms over four per cent, of
the weight of the maternal part, and it gradually increases till the
eighteenth day, when it forms 5*5 per cent. ; it remains nearly
constant till the twenty-second day, and then there is a continuous
decrease each day till the end of pregnancy. On the day before
labour it amounts to slightly over one per cent., and practically the
whole of it is situated at the zone of separation. This last is
probably not destined for the foetus.

The variations in the proximal glycogen are similar. At the
twenty-ninth clay there is no glycogen left in the intermediary region.

In the foetal liver traces of glycogen are present at the eighteenth
day, though none can be demonstrated histologically till four days
later. Up to the twenty - fourth day" the percentage gradually
increases, but is still very small. Next day it rises for the first tune
above the glycogen percentage in the rest of the fcetal body, and
then there is a rapid increase till, on the twenty-ninth day, half of
the foetal glycogen is stored in the liver. Hence it may be concluded
that, although the liver contains glycogen in the earlier stages, a
change occurs at the twenty-fifth day of pregnancy. Only then does
it store more than its proportion of glycogen by weight, and thus
may be said to bs capable of carrying on the glycogenic function for
the foetus. Before that date the only store of glycogen available is
contained in the maternal placenta. " The glycogen metabolism of the
placenta and foetus shows a regular succession of changes which
proceed almost regardless of external conditions, and which are
independent to a great extent of the glycogen metabolism of the
mother " (Lochhead and Cramer).

There can be little doubt that the glycogen stored in the decidual
cells is absorbed by the trophoblast. It is situated in the maternal
peninsula? which are surrounded by fcetal tissue, and it gradually
decreases in amount while it increases in the fostus. That none can
be demonstrated in the trophoblast may be due to a transformation
into sugar before it is absorbed. Glycerine extracts of both the
maternal and the foetal part of the. placenta possess an enzyme which
has a powerful hydrolytic action on glycogen. On the other hand,
the enzyme action is markedly weaker, or absent altogether, in the
placentas of Euminants, in which the glycogenic changes are known
to be insignificant.

It is not easy to determine why such a complex mechanism is
necessary if, as is stated by Cohnstein and Zuntz,1 glucose passes
from the maternal to the foetal circulation by diffusion. But these
investigators have only proved that it diffuses, when a hyperglycremia

1 Cohnstein and Zuntz, " Weitere Untersuchungen zur Physiologic der
Saugetierfotus," Pjluger's Arch., vol. xlii., 1888.

FCETAL NUTRITION: THE PLACENTA 463

exists in the mother. Under similar conditions glucose passes into
the urine and liquor amnii in man, but it does not pass normally.1
Hence it has not been proved that the sugar of the maternal blood is
diffused unchanged through the trophoblast. It is more probable
that the transference of sugar is not effected by a purely physical
process, since the serum of the fostal rabbit contains hevulose, while
the serum of the mother has none (Paton, Kerr, and Watson 2).

Between the glycogen metabolism and the growth of the foetus
there is a distinct relationship, which probably depends directly on
the uses to which glycogen is put. Part of it is accounted for by the
intense carbohydrate metabolism which proceeds in the foetus (Bohr 3).
The glycogen, which is thus katabolised, furnishes thereby the energy
necessary for the formation of new tissues, the " Entwicklungsarbeit "
of Tangl.4 The question arises whether glycogen also performs
anabolic functions in the development of the foetus. " The absence
of glycogen from some of the growing foetal tissues, and the fact that
many of the tissues in which it is present do not contain even as
much as the adult ones, leave little doubt that a definite formative
power cannot be attributed to glycogen as such. On the other hand,
the scarcity of glycogen in embryonic tissues does not necessarily
justify the conclusion that glycogen does not take part in the building
up of the tissues. It is well known that embryonic tissues are rich
in mucin, which contains a large amount of a carbohydrate group in
its molecule. Although glycogen as such has no formative power, it
may yield one of the ' Bausteine ' for the building up of the main
protein body of foetal tissues. In this connection it is interesting to
consider the conditions in the hen's egg, which contains in itself the
material of which the embryo is built up.5 In the ovum carbohydrate
as such is practically absent. At the same time all the protein
substances of the white of egg are distinguished by the presence of a
large amount of glucosamine in their molecule. Here the carbohydrate
group has entered into the protein molecule, and correspondingly
there is a scarcity of free carbohydrate."6

1 Even in the hyperglycsemia of diabetes the figures do not support the
theory of the mere diffusion of glucose. Offergeld found 0'8 per cent, of sugar
in the maternal blood, and 2-2 per cent, in the foetal blood in diabetic coma
(" Ueber das Vorkommen von Kohlehydraten im Fruchtwasser bei Diabetes,"
Zeit. f. Geb. u. Gyniik., vol. li.).

2 Paton, Kerr, and Watson (B. P.), " On the Source of the Amniotic and
Allantoic Fluids in Mammals," Trans. Roy. 8oc. Edin., vol. xlvi., 1907.

3 Bohr, " Die respiratorische Stoffwechsel des Saugetierembryos," Skand.
Arch. f. Pkysiol., vol. x., 1900. See also vol. xv., 1904.

4 Tangl, " Beitriige zur Energetik der Ontogenese," Pfliiget's Arch., vol. xciii.,
1903.

5 Compare Emrys-Eoberts, " A Further Note on the Nutrition of the Early
Embryo, with Special Reference to the Chick," J'roc. Roy. Soc. L,<mdon, B., vol.
Ixxx., 1908.

6 Lochhead and Cramer, loc. cit.

464 THE PHYSIOLOGY OF REPRODUCTION

Protein Metabolism

In so far as the influence of the trophoblast on proteins has been
investigated in the placenta of the rabbit, it may be considered here.
It is generally accepted that colloid substances with large molecules,
which are not adapted for diffusion, require a preliminary transforma-
tion, by which the size of the molecules is decreased before they can
be taken up by the foetal ectoderm. But the actual observations are
against such a general statement. In the sheep the trophoblast can
absorb not only haemoglobin, a colloid, without any preliminary
transformation, but even enormously larger masses of protoplasm in
the form of cells. On the other hand, such hydrolysed products of
albumen as albuuioses and peptone are not present in the fresh
placenta, nor can any extra-cellular proteolytic enzyme be extracted.1
Hence there is no evidence of a placental digestion of proteins before
their absorption by the trophoblast. Further, it has been shown, by
means of the precipitin reaction, that if egg-albumen is injected into
the mother some of it passes unchanged to the fetus ( Ascoli 2). On
the other hand, the proteins of ox-serum cannot be recognised in the
foetal blood, even when a considerable quantity is injected.3 The
reason appears to be that the proteins of ox-seruin resemble more
closely the normal serum proteins of the rabbit and are metabolised
by the trophoblast, while egg-albumen cannot be utilised, and is
passed on to the foetal circulation unchanged. Hence it- is probable
that the normal proteins of the serum are also transformed by the
trophoblast into a form suitable for the foetus. The exact nature
of the transformation is unknown, but it is not comparable with the
hydrolytic processes which occur in the intestine.

Respiration

According to Bohr,4 the foetal rabbit absorbs slightly more oxygen
and gives off slightly more carbonic acid per kilogram per hour than
the mother. Hence the intensity of the metabolic reactions is slightly
greater in foetal life. This is directly opposed to the views held by
Pfliiger on theoretical grounds, and by Cohnstein and Zuntz 5 from
their experimental results. The second result of Bohr's experiments
has been already mentioned, viz. that in that part of the metabolism

1 Lochhead, " Oil the Transmission of Nitrogenous Compounds from Mother
to Foetus," Tram. Obstet. Soc. Edinburgh, vol. xxxiii., 1907-08.

2 Ascoli, "Passiert Eiweissdie placentare Scheidewand?" Zeit.f.physiol. C/mm.t
vol. xxxvi., 1902. This has been confirmed by the writer and Dr. W. Cramer
(see reference, note '.

3 Lochhead, loc. cit.

4 Bohr, loc. cit.

5 Cohnstein and Zuntz, " Untersuclmngen iiber das Blut, den Kreislauf und
die At mini g der Saugetierfotus," PJIilget's Arch., vol. xxxiv., 1884.

FCETAL NUTRITION: THE PLACENTA 465

which is evidenced by the respiratory exchange, the energy arises
from carbohydrates. He arrived at this conclusion as a result of
determining the respiratory quotient l in pregnant rabbits and guinea-
pigs before and during the compression of the umbilical cord, the
difference representing the respiratory exchange in the embryo.
He found that the quotient in such cases was unity, thus showing
that the substance oxidised in the developing embryo must have
been a carbohydrate. Bohr supposed that the energy liberated by
the combustions, which in the adult is dissipated largely under the
form of heat radiated and water evaporated from the surface of
the body, is in the fetus used for the increase and maintenance of
the newly formed tissues ; in other words, " the reactions of synthesis,
which are so numerous during development, are eudothennic or
heat-absorbing, and they borrow the heat from other simultaneous
exothermic actions," 2 in this case the oxidation of carbohydrates.

Ferments and Vital Staining

Frank3 has carried out an investigation to determine whether
any differences existed in the ferment content of the functionating
as compared with that of the non-functionating placenta. His
results were mostly negative, no definite evidence/ being afforded
either for or against the view that the placenta acts as an accessory
organ of metabolism to the foetus. The experiments were mainly
upon the rabbit.4 The ferments investigated were amylase (or
starch hydrolysing ferment), lipase (fat splitting), and erepsin
(hydrolysing peptone to amino-acids), and their respective contents
were determined by appropriate tests. The amy]ase content was
the same or less than that of the maternal blood, the lipase rather
more, and the ereptic content considerably more. The foetal blood
contained less ferments than the maternal. Neither foetal nor
maternal blood showed any changes in ferment strength in relation
to the progress of pregnancy. The organs of large foetuses have
high ferment values, sometimes higher than those of the corre-
sponding organs in the mother. The investigation upon "vital
staining," in whicli the acid stain " trypanblau " was injected

1 The respiratory quotient is the ratio of CO2 discharged to Od absorbed,

V'O
that is, the fraction -— ^. For an exclusively carbohydrate food this is unity ;

2

for a fat or protein, less than unity. For a discussion of the subject in

i-elation to ftetal metabolism see Feldman, Principles of Antc-Xatal and Post-
Natal Child Physiology, London, 1920. See below, p. o04.

2 See Richet's IHctionnairc de Physiologic, vol. vi., Article " Fuetus."

3 Frank, ''An Experimental Study of the Placenta, etc.," Pfurff., Gyn. and
Obstct., November 1912.

4 The animals used were six rabbits, three guinea-pigs, two cats, and a
bitch.

466 THE PHYSIOLOGY OF REPRODUCTION

subcutaneously into pregnant rabbits and guinea-pigs, was carried
out to supplement the research upon the ferments. The evidence
obtained, according to Frank, favoured the view that the placenta
is a passive organ of exchange rather than an active organ of
metabolism. The uterus was found to take the stain first; next
the yolk membrane, and last the placenta. The kidney and liver
in the foetuses readily absorbed the dye but other organs were
affected. Goldmann1 has also investigated the effects of vital
staining and traced the paths by which the dye (trypan or pyrrol
blue) enters the foetus, and has made a careful study of the behaviour
of the placenta towards vital stains. Of especial interest is the
marked reaction of the wandering connective tissue cells ("pyrrol
cells ") to the vital stain.

Wislocki2 found that when trypan or pyrrol blue are injected
intravenously into the pregnant rabbit, as with the guinea-pig, mouse,
and rat, traces of the colloid may pass into the amniotic fluid, and
even stain the foetus. In the case of the cat, however, they only
reach the placenta and are stored in the form of granules in the
chorionic ectoderm. Wislocki concludes, therefore, that the placenta
of the carnivore is less permeable than that of the rodent. Colloidal
dyes injected into the amniotic cavity of the cat and guinea-pig
in later pregnancy are absorbed through the gastro-mteatinal and
respiratory tracts and by diffusion through the amniotic membrane.
The foetus becomes vitally stained, but none of the colloidal material
passes into the maternal circulation. Wislocki also administered
intravenously a solution of India ink to pregnant rabbits and other
animals, and found that neither the chorionic epithelium nor the
placental endothelium could absorb or phagocytise granules as coarse
as this, and the placental and foetal membranes were entirely un-
stained. Phenolsulpho-naphthalein injected into the foetal peritoneal
cavity is absorbed by the blood-stream, passes to the placenta,
and thence to the maternal circulation and kidneys; it is also
excreted by the foetal kidneys. Trypan blue (a less diffusible colloid),
when similarly injected, vitally stains the foetus, is excreted by the

1 Goldmann, "Neue Untersuchungen iiber iiussere und innere Sekretion
des Gesunden und Kranken Organismus im Lichte der 'Vitalen Farbung,'"
Tubingen, 1912 ; repriri*ted from Beiti\ zur klin. Chir., vol. Ixxviii., 1912.
This memoir, which contains many references to literature, includes also a
detailed account of the investigation of the glycogen, fat, iron, and haemoglobin
absorption through the placenta by microchemical methods. The methods of
vital staining have been taken advantage of in their application to the study
of the cell nucleus by Kite and Chambers (" Vital Staining of the Chromosomes
and the Function and Structure of the Nucleus," Science, vol. xxxvi., (November)
1912.

2 Wislocki, "Experimental Studies on Fetal Absorption," I. to IV., Contri-
butions to Embryology, vols. xi. and xiii., Carnegie Institute (Washington)
Publication 276, 1920-21. See also Johns Hopkins Hospital Bull., vol. xxxii.,
1921 ; and Anat. Rec., vol. xxi., 1921.

FOETAL NUTRITION: THE PLACENTA 467

foetal kidneys, but does not traverse the maternal placenta and enter
the maternal circulation.

Mouse. — The fertilised ova of the mouse reach the uterine cavity
on the third day, and segmentation is completed one day later. The
zona pellucida has by this time disappeared, and fixation of the
ovum to the uterus can be quickly attained. Each blastocyst comes
to rest in an anti-mesometrial groove. At first spherical, it becomes
ovoid on the sixth day, with the long axis perpendicular to ;the long
axis of the uterus. One pole is turned towards the mesometrium and
is composed of several layers of cells, while the opposite pole is single-
layered. It is nourished by the glandular secretion, and perhaps also
by a transudate, in which, however, leucocytes are not present.

The connective tissue of the mucosa shows a thickening at the
point where a blastocyst rests. The epithelium degenerates as
the result of contact with the foetal ectoderm (Duval1), or of
pressure by the proliferated connective tissue cells which interferes
with the nutrition of the epithelium (Burckhard2), More probably
it is not mechanical, as the change begins first at the mouth of the
groove, i.e. at the point of first contact with the ovum (Kolster3).
In the cells the chromatin clumps on the inner surface of the nuclear
membrane, the cell boundaries disappear, and a symplasma is formed
which later becomes broken up into nuclear and cellular fragments.
Fat globules, which are present in the epithelium of the non-pregnant
uterus, are found in the detritus and also in the fostal ectoderm.

With the destruction of the epithelium appears the first sign of
decidual formation. The connective tissue cells increase in size and
displace the glands ; the capillaries dilate irregularly, and at places
form sinuses.

On the sixth day the ectoplacental cone is formed by a proliferation
of the ectoderm at the mesometrial pole of the blastocyst. It plugs
the opening between the crypt and the lumen of the uterus. At the
same time the lips of the crypt are gradually brought nearer to each
other by the swelling of the tissues, and at the end of the seventh
day they fuse and cover the ectoplacenta. In this way the ovum is
completely shut off in -a decidual cavity, the " Eikammer," from the
uterine lumen. The roof of the chamber forms the primary decidua
retiexa, and it is gradually thickened by a decidual deposit. In it
new blood-vessels are developed, and they form a specially rich
vascular network.

1 Duval, "Le Placenta des Rongeurs," Jour, de I'Anat. et de la Phys., 1891.

2 Burckhard, " Die Implantation des Eies der Maus in die Uterinschleim-
haut," Arch. f. mikr. Anat., vol. Ivii., 1901.

3 Kolster, " Zur Kenntnis der Embryotrophe beim Vorhandensein einer
Decidua Capsularis," Anat. ffefte, vol. xxii.

468 THE PHYSIOLOGY OF REPRODUCTION

By tliis time the blastocyst has become tubular in shape, and it
shows an inversion of the germinal layers (Fig. 132). In the earlier
stage a cavity appears in the inner mass of cells. The roof of the
cavity becomes thickened to form the "Trager" or ectoplacental
cone, which is at first cylindrical and later conical, with its base
resting on the mesometrial pole of the ovum. By its inward growth
it shoves before it the floor of the inner
mass consisting of epiblast and hypoblast.
In this way an invagination is produced in
the tube with the epiblast internal to the
hypoblast. Hence the germinal layers are
said to be inverted.

Blood is regularly found in the im-
plantation cavity. It completely surrounds
the ovum, and reaches irregular spaces in
the ectoplacenta which communicate with the
surface. At this time, however, there are
no fcetal vessels near the cone, and the
blood in its meshes may be of use only
for its own nutrition. On the other hand,
the thin trophoblast of the wall of the in-
vaginated yolk-sac is partly vascularised
by vitelline vessels, by means of which the
nutriment absorbed from the blood effusion
may reach the embryo or be stored in the
yolk-sac. In the trophoblast itself the
hfemoglobin of laked corpuscles and its
derivatives are present (Jenkinson1), and
the contents of the umbilical vesicle are
"not yolk, but another nutritive substance
which the ovum, in the -absence of yolk,
takes from the maternal tissues, viz. haemo-
globin " (Sobotta 2).

The clecidual cavity is at first small and
ovoid, and has a thick wall. As it grows,
the lumen of the 'uterus is obliterated,
and at its point of contact with the mesometrial wall the
epithelium of the latter disappears. Thereafter the two layers
fuse, and at the point of fusion the placenta is developed. The
lumen of the uterus is later re-established, as in the guinea-pig (see
Fig. 137), at the floor of the decidual cavity. Hence the primary

1 Jenkinson, " Observations on the Histology and Physiology of the Placenta
of the Mouse," Tijd. Nederl. JJierk., Ver. ii., Dl. vii.

2 Sobotta, "Die Entwicklung der Maus," Arch.f. mikr. Anat., vol. Ixi., 1903.

FIG. 132. — Inversion of
the germinal layers
in the blastodermic
vesicle of the mouse.
The trophoblast be-
comes greatly
thickened and in-
vaginated, pushing
the formative epi-
blast before it. The
whole blastocyst
assumes a tubular
shape, and the
hypoblast appears
to be external to the
epiblast. Tropho-
blast represented
by continuous black
lines or masses :
entoderm by inter-
rupted lines : em-
bryonic ectoderm
by epithelial cells.
(T. H. Bryce, in
Quoin's Anatimii/,
Longmans.)

FCETAL NUTRITION: THE PLACENTA

469

decidua reflexa forms the serotina, and a secondary retiexa is formed,
which is recognisable till the twentieth day of pregnancy.

The increase in size of the implantation cavity is accompanied
by a thinning of its wall. According to Duval this is a mechanical

sym.

FIG. 133. — Longitudinal section of the implantation cavity of the field-mouse
about the eighth day of pregnancy. (From Disse's " Die Vergrosserung
der Eikammer bei der Feldmaus (Arvicola arvalis)" Arch. f. mikr. Anctf.,
vol. Ixviii., 1906.)

p/, Placental pole ; mph, macrophags or giant-cells ; aym, uterine
symplasma ; I, blood lacuna.

process, s,ince the cells do not increase in number, but it is probably
more complicated. On the inner surface of the decidua giant-cells
appear around the ovum, and they are phagocytic (Fig. 133). Duval
stated that each was derived from a cell of the foetal ectodermal
wall of the yolk-sac, and later from a cell of the ectoplacental cone.
As they increase in number, they form a distinct layer, two to five
cells in depth, between the yolk-sac and the wall of the implantation

470 THE PHYSIOLOGY OF REPRODUCTION

cavity, and some wander into the decidua and lie singly or in
groups. In their interior degenerating leucocytes are frequently
seen. Sobotta also stated that they were festal in origin, and helped
to fix the ovum and erode maternal capillaries. More recently
Kolster has brought forward evidence from their histological appear-
ance that they are transformed decidual cells, and this is strongly
supported by Disse's investigations on the field-mouse,1 in which the
giant-cells are found before the ovum has become embedded, and
the first to appear are at an appreciable distance beneath the surface
epithelium. A second series of smaller size appears later in the
lumen and wall of the implantation cavity. Jenkinson also recognised
two groups, but assigned to them different origins, fetal in the
" Eikammer " and maternal in the decidua.

All authorities agree that they are phagocytic. The tissue
around them undergoes fatty degeneration, and in their interior
may be seen remnants of connective tissue and endothelial cells and
fat globules. Many capillaries are 'ruptured, and red and white
blood corpuscles are also absorbed. Such an absorption of maternal
tissue by the giant-cells leads to an increase in the size of the
implantation cavity and a thinning of its wall (Disse). In spite of
their abundant supply of nutriment, their life-history is short. No
cell-divisions occur, and soon they degenerate. Their contents are
absorbed by the trophoblast, and their protoplasm shrinks to form
a rim around the nucleus. Later still their remnants are also
absorbed.

The allantois in the mouse is a solid mass of mesoderm with no
entodermal cavity. Growing out from the posterior end of the
embryo, it projects into the extra-embryonic cceloni, and on the
eleventh day fuses with the mesoblast of the ectoplacental cone.
After this the ovum again becomes spherical. The circulation in
the decidua reflexa diminishes, and gradually more and more of the
nutriment is conveyed to the embryo by the allantoic vessels. At
the same time the allantoic trophoblast increases in thickness, and
its lacunae become more numerous and complicated. Into its mass,
in which the circulation of maternal blood is now established, the
vascular mesoblast projects at intervals, and breaks it up into
segments. The glands take no part in the formation of the placenta.
Their ducts do not even act as guides to the advancing edge of the
trophoblast, as in the rabbit. They are completely displaced by the
rapid formation of decidual tissue, and their remnants are absorbed
by the giant-cells. Hence the embryotrophe contains no glandular
secretion.

1 Disse, "Die Vergrosserung der Eikammer bei der Feldmaus," Arch. f. mikr.
Anat., vol. Ixviii., 1906.

FCETAL NUTRITION: THE PLACENTA 471

At this time the nutritional conditions are essentially the same
as in the rabbit. The trophoblast shows two layers, plasmodiblast
and cytoblast, which intervene, along with mesoblastic cells and the
walls of the villous capillaries, between the two blood-streams. The
subsequent changes are all in the way of producing an increased
surface of contact with maternal blood, and lessening the thickness
of tissue between it and the foetal circulation.

En the mouse the decidual cells contain glycogen. According to
Driessen,1 its distribution in the placenta of the white mouse before
mid-term is the same as in the rabbit. It is in great abundance in
the decidual cells, especially in the boundary layer between the
maternal and foetal tissues. No glycogen is found in the maternal
endothelium or in the foatal placenta. Jenkinson2 has studied the
distribution of glycogen throughout the whole period of gestation in
the mouse. It appears first in the cells which overlie the ecto-
placenta, and increases in amount till the twelfth day, when the
mesoblastic processes are just beginning to project into the tropho-
blast. Then the decidual cells are disintegrated and the glycogen
granules are mixed with the detritus. Hence the life-history of the
maternal glycogenic tissue is shorter than in the rabbit. But in
the mouse glycogen again makes its appearance in the trophoblast
which is most directly in contact with the maternal' blood, i.e. the
part not penetrated by the allantoic capillaries. It lies in oblong
ectodermal cells, which gradually encroach on and occupy the
space previously occupied by the maternal glycogenic cells down
to the muscularis. Here the glycogen remains till the end of
gestation.3

" There can be no doubt that this tissue holds in reserve a store of
food material for the use of the embryo. As sugar the glycogen
passes into the maternal vessels and into the lacume, and so is
absorbed by the fostal capillaries. When the glycogen is used up
the cells collapse, and their collapse may be a factor in determining
the moment of parturition, since it is across this layer that • the
placenta breaks away. The trophoblastic is much more voluminous
than the maternal glycogenic tissue ever was " (Jenkinson 4).

According to Kolster, a considerable amount of fat appears in the
decidua, in which the connective tissue and endothelial cells undergo
a fatty degeneration in the proximity of the giant-cells. No observa-

1 Driessen, "Ueber Glykogen in der Placenta," Arch. f. Gyniik., vol. Ixxxii.,
1907.

- Jenkinson, loc. cit. See also Brit. Med. Jour., 1904.

3 Whether the differences in the distribution of the placental glycogen
in the rabbit and the mouse during the later stages of pregnancy exist in
reality, or depend only on differences of interpretation, requires further
investigation.

4 Jenkinson, Vertebrate Embryology, Oxford, 1913.

47^ THE PHYSIOLOGY OF REPRODUCTION

tions have been made regarding the metabolism of iron-containing
substances.

<iuima-Pig. — In the guinea-pig the ovum is again completely
surrounded by decidua. Reichert l was the first to notice that the
ovum lay in a special cavity, " a little nest." Bischoft'2 stated that
the nest was only temporary, and the ovum again appeared in the
uterine cavity, only that part of the nest remaining which formed
the placenta. After a long interval this was proved to be wrong by
Reichert 3 and Hensen.4

The fertilised ovum reaches the uterus as a niorula or early blasto-
cyst, surrounded by the zona radiata. On the seventh day the zona

FIG. 134. — Longitudinal section of the uterus and implantation cavity of the
guinea-pig. (From Duval's "Le Placenta des Rongeurs," Journ. de FAnat.
et de la I'/iys., 1892.)

ine#, Mesometrial border ; gl, uterine glands ; /, uterine lumen ;
W, blastodermic vesicle.

disappears and embedding begins, but even before this, according to
von Spee,5 the ovum is fiied by processes which extend from the cells
of the implantation pole through the zona and come into direct
metabolic relationship with the epithelial cells. As in the mouse,
the blastocyst remains small, about one-tenth of a millimetre in
diameter. At its point of contact with the mucosa, the epithelium is
rapidly eroded, and absorbed along with its fat globules by the foftal
ectoderm. At the same time changes occur in the deeper layers. In

1 Reichert, " Ueber die Bildung der hinfiilligen Haute der Grebarm utter,"
Miller's Arch., 1848.

2 Bischoff, Entivicklung des Meerschweinchens, 1852.

3 Reichert, "Beitrage zur Entwicklungsgeschichte des Meerschweinchens,"
Abhandl. d. Akad. d. Wissensch. zu Berlin, 1861.

4 Hensen, " Beobachtungen iiber die Befruchtung und Entwicklung d«-s
Kaninchens und Meerschweinchens," Zeit. f. Anat. u. Entu'ick., vol. i., I860.

6 Von Spec, "Die Implantation des Meerschweincheneies in die 'Uterus-
wand," Zeit. f. ^forphoL u. Anthropol., vol. iii., 1901.

FCETAL NUTRITION: THE PLACENTA

473

the non-pregnant uterus two layers are present, a sub-epithelial
layer of embryonic connective tissue cells interrupted only by
capillaries and glands, and a deeper, more reticulate layer. Before
the ninth day of pregnancy, no very marked changes occur in the
mucosa. Some of the cells show mitoses, the blood-vessels are full,
and a few red blood corpuscles may lie between the cells, and also in
the foetal ectoderm. During the penetration of the epithelium by
the trophoblast, some of the superficial con-
nective tissue cells enlarge. Their nuclei
stain more deeply, and the protoplasm of
adjacent cells fuses to form a symplasma.
The degenerated tissue in its immediate
neighbourhood is absorbed by the ectoderm,
and the blastocyst thus comes to lie in the
substance of the mucosa (Fig. 134). Accord-
ing to von Spee, the destruction of uterine
tissue is effected entirely by a biochemical
process; there is no evidence of absorption
of formed elements by phagocytosis.

Round the periphery of the necrotic
zone lies a thick layer of large foetal cells,
the two together forming the "Implanta-
tionshof." Later the symplasma degener-
ates further. The nuclei shrink and lose
their chromatin, and the protoplasm be-
comes fibrillated and granular. Vacuola-
tions appear in the mass, and coalesce to
form a space round the ovum filled with
clear fluid. In this way the implantation
cavity is excavated till it is limited exter-
nally by the large cells. Outside it the
decidual cells around the vessels survive,
while the rest are transformed to a sym-
plasma and absorbed. Hence the wall is
sinuous. The dips are, however, filled up in
part by newly formed tissue resembling • granulation tissue. It
encapsules the necrotic zone, and may be looked on, as in the rabbit,
as a defence against the advancing ectoderm (see p. 403).

By this time the ovum has become tubular, with its long axis
perpendicular to the long axis of the uterus. It exhibits, as in the
mouse, an inversion of the germinal layers, but .in the guinea-pig the
amnio- embryonic vesicle is closed and separates the thickened tropho-
blast from the embryonic ectoderm (Fig. 135). With the growth of
the blastodermic vesicle, the roof of the implantation cavity projects

FIG. 135. — Blastodermic
vesicle of the guinea-
pig, showing inver-
sion of the germinal
layers. The blasto-
cyst is tubular, and
the formative cell-
mass is invaginated
as in the mouse, but
the thickened tro-
phoblast is not in-
vaginated to so
great an extent as
in Fig. 132, and the
connection between
them is lost. Hence
the roof of the
amnio-embryonic
cavity is independ-
ent of the tropho-
blast. (T. H. Bryce
in Quain's Anatomy,
Longmans.)

474 THE PHYSIOLOGY OF REPRODUCTION

into the lumen of the uterus, and in time obliterates it by coining in
contact and fusing, at the tenth day, with the mesometrial mucosa
(Fig. 136). Here also the cellular tissue has developed at the expense
of the glands, and the surface epithelium disappears. At the fifteenth
day the lumen reappears anti-mesometrially (Fig. 137)'. Thus a
secondary decidua reflexa arises which rapidly thins and becomes
vacuolated in its inner half by a loss of tissue. The cause of the
tissue excavation is uncertain ; it may be brought about by the large
cells which, according to von Spee, are foetal and form a third layer
of the trophoblast outside the plasmodiblast, and the disintegrated
products are probably absorbed by the ovum. At the same time the

mes

^s.

FIG. 136. — Implantation cavity of the guinea-pig. (Duval.)
mes, Mesometrial border ; I, uterine lumen*

vessels which penetrate the necrotic zone are opened, and blood is
effused into the implantation cavity.

The placenta develops, as in the mouse, mesometrially. The
allantois consists of a tubular passage in the body wall and a solid
extra-embryonic stalk of mesoderm. It projects into the coelom and
gradually extends, and becomes applied to the mesoblast underlying
the thickened part of the trophoblast, in the spaces of which a
circulation of maternal blood is established. The trophoblast continues
to attack and absorb maternal tissue and blood, and to advance more
deeply into the decidua, while at the same time it is penetrated on
the embryonic side by outgrowths of mesoblast containing branches
of the allantoic vessels. The tissues intervening between the maternal
and f ratal blood-streams are entirely foetal ; they gradually thin with
the progress of gestation and the continued branching of the meso-
dermal villi.

FCETAL NUTRITION: THE PLACENTA

475

Glycogen is contained in the clecidual cells, but its variations
have not yet been investigated. It is of interest historically that
oxyhsemoglobin was demonstrated first in the umbilical vein of a
foetal guinea-pig by Schmidt.1 The amounts of oxygen absorbed and
carbonic dioxide excreted are the same, weight for weight, as in the
fcetal rabbit (Bohr). (See above, p. 464.)

Fat is widely distributed in the foetus, and Hof baur 2 has shown
that the fatty acid of a fat ingested by the mother guinea-pig may be
transmitted across the placenta to the foetuses. The mother was fed
•on coco-nut oil which consists largely of triglycerides of laurinic and

am

FIG. 137. — Implantation cavity of the guinea-pig. (Duval.)

mes, Mesometrial (placenta) border ; I, lumen of uterus, re-established anti-
mesometrially ; d./:, decidua reflexa ; all, allantois ; am, amnion.

inyristinic acids, and considerable quantities of laurinic acid were
afterwards found in this guinea-pig's foetuses (see p. 543).

Beaver. — The connecting membrane, or " Haftstiel," and the part
it plays in this animal have already been referred to (p. 423).
Another noteworthy feature is the abundance of erythrocytophagous
and leucocytophagous cells. There is no bleeding into the uterine
cavity, but the maternal capillaries, which are very numerous, abut
upon implanted megalokaryocytes and discharge the red corpuscles
directly into the trophoblast. The extravasated erythrocytes are all
ingested by megalokaryocytes. Migrating leucocytes in large numbers
are also absorbed by the large phagocytic cells.

1 Schmidt, " Sauerstoffhamoglobin in Fotusherzblut," Cent. f. d. med. Wiss..
J 874, No. xlvi.

3 Hofbaur, Grnndzilge einer Biologic, der MensehHeken Plazenta, Leipzig, 1905.

476 THE PHYSIOLOGY OF REPRODUCTION

The trophoblast of the beaver in the preplacental stage is at the
areas of attachment not more than one layer in thickness. It does
not send processes to any depth into the mucosa, but has a flat
insertion upon the decidual surface, the maternal capillaries pressing
towards the trophoblast rather than otherwise. Whenever the uterine
epithelium is displaced by the ob-placental trophoblast it disappears
without forming a syncytium. The uterine epithelium probably
becomes necrotic in advance of the trophoblastic growth, and the
latter does not destroy the epithelium which is normal at the borders
of the decidual surface.1

INSECTIVORA. — The importance ascribed to the placentation in
Tnsectivora has already been referred to (see p. 409). The hedgehog,
shrew, mole, and Tupaia have been most fully investigated.

Hedgehog. — In the hedgehog (Erinaceus europceus). the zona
pellucida disappears early, before the expansion of the hypoblast,
which, as in man, forms a closed vesicle. The chronology of
embedding is not yet known. In the earliest stage examined by
Hubrecht,2 the blastocyst was 0-22 of a millimetre in diameter. The
outer wall was several layers thick all round its circumference, and
spaces were already present in it. At a slightly later stage the
blastocyst grows rapidly and the epiblast is reduced to a single layer,
with numerous villiform processes at intervals, except for a thickened
knob which represents the future germinal area. Even now the
name trophoblast may be given to the single layer of epiblast with its
projections, excluding the thickened knob which is formative and
gives rise to the embryonic ectoderm and the lining of the amuiotic
cavity. The mesoblast, as yet one-layered, which extends between
the trophoblast and hypoblast, consists of an attenuated somatic part
which forms with the trophoblast the diplo-trophobtast,3 and a
splanchnic part which forms blood-vessels and blood.

The early blastocyst comes to rest, as in the mouse, in an auti-
mesometrial furrow of the mucosa. It is not yet determined whether
any changes occur previously in the uterus ; but at least, soon after
the blastocyst has taken up its position, there is a great cell-
proliferation in the stroma of the floor and walls of the furrow, not
perivascular as in the rabbit, but sub-epithelial. Along with this
decidual formation, the lumina of the glands are closed, and their
epithelium gradually disappears, perhaps by the influence of the

1 Willey, "The Blastocyst and Placenta of the Beaver," Quar. Jour. Mi<r.
Science, vol. lx., 1914.

2 Hubrecht, " The Placentation of Ennaceiis evropceiis" fyuar. Jour. Micr.
Science, vol. xxx., 1889.

3 Hubrecht restricts the term chorion to Tarsixs (a lemur), monkeys, apes,
and man (see p. 490).

FCETAL NUTRITION: THE PLACENTA

477

trophoblast. The capillaries are distended and new vessels are
formed. This distension is at first most marked in the lips and sides
of the groove, and small superficial haemorrhages occur, which detach
the epithelium at places. The tissue fluids also exude, and, along
with the blood and desquamated epithelium, form a coagulum around
the ovum. Part of it shuts off the entrance of the furrow from the
uterine cavity.

The epithelium of the crypt, after a preliminary proliferation
such as Eobinson describes in the mouse and rat, degenerates

Tr.S.

• F.L.

M&^mmm

-;;- ^i*&/:' /'}".'

Sp.

M.Som.

FIG. 138. — The allantoidean diplo-trophoblast of Erinaceus. (From Hubrecht's
"The Placentation of Erinaceus europceus," Quar. Jour. Micr. Science,
vol. xxx., 1889.)

Tr.S., Trophospongia ; 7V., trophoblast ; F.L., layer of fusiform cells ;
Sp., spaces in trophoblast ; M.Som., thin layer of somatic mesoblast.

entirely, part being stripped off by extravasated blood and part
yielding to the influence of the foetal ectoderm. Its remnants and
the other constituents of the coagulum probably furnish pabulum
for the ovurn. The development of the decidua proceeds rapidly,
and the swollen lips of the groove fuse together to complete the
implantation cavity. The trophoblast is now in contact with
decidual tissue, of which the innermost zone consists of a stratified
layer of fusiform cells, best marked in the allantoic region (Fig. 138).
Whether they are maternal or foatal in origin is not yet determined.
They persist for a time, but disappear when the endothelial pro-
liferation occurs. Around the groove the tissue becomes looser by
an increase in the size of the newly formed blood-spaces. The

478 THE PHYSIOLOGY OF REPRODUCTION

endothelium lining them is swollen and deep, and the cells bulge into-
the lumen. Near the ovum the endothelium proliferates and forms
an enormous cell-mass, the trophospongia,1 interposed between the
blastocyst and the unaltered decidua. The trophoblast with its
lacunse, and the trophospongia with large blood-sinuses together form
the trophospherc, which, along with the maternal blood, represents an

%. -4S^Bl^

' Jj "". - v- - • •; .

' * ""* . 'r?.&!»'le» '.

*••» tfrZfj • • .••, '

M
,,. *-X3gm

' *r -»Af* ' *^> -9W'' >

Mr

/>

>it*^ ' TVs.
to

Trs.

& ",\.

FIG. 139. — Section in situ of the ovum of Ennaccus (Hubrecht).

Hi/., Hypoblast ; TV., trophoblast ; sp., spaces in the trophoblast, communi-
cating with the maternal blood-spaces (M.8p.) ; /)., decidua ; Trs.f
trophospongia.

effective nutritional arrangement for the embryo before the vitelline
or allantoic circulation is established (Fig. 139). Many of the
blood-spaces are ruptured, and the -blood pours out into the lacunse
of the trophoblast, and circulates through them before returning into
the maternal veins. At this stage the trophospongia is separated
from the external decidua by rows of fusiform cells.

As in the mouse, in which, however, the trophospongia is derived

1 " The trophospongia is a maternal cell-proliferation specially intended for
the fixation of the blastocyst. It shows a different histological evolution in
different genera " (Hubrecht).

FCETAL NUTRITION: THE PLACENTA 479

from connective tissue cells instead of endothelium, giant-cells
appear. They lie between the trophospongia and the fusiform cells,
and they are first seen at the time of the appearance of the embryonic
mesoblast. In their interior are contained fragments of red blood
corpuscles and decidual cells. Hence they are called deciduo-
fracts by Hubrecht (Fig. 140). Externally the circular layers of
fusiform cells form sheaths round some of the endothelium-lined
vessels. The line of union between the giant-cells and the external
decidua is irregular, and the decidual tissue is fibrillar and reticulate.

TV. TV*. Df.

**£;'••'& '*?'>•.'•* >'• ** •«" -'

*t\f<( • V'.UNk

> V:-v ;'•>••

Df. I)' I)

FIG. 140. — The extension of the yolk-sac against the lacunar trophoblast in
Erinacctis (Hubrecht). The yolk-sac is to the left of the figure, and its
villi ( Vi.) and blood-vessels (/). V.} are well seen.

TV., Trophoblast ; TV,?., trophospongia ; Df., layer of deciduofracts ; />.,
decidua, of which the inner layer (//) has assumed a more reticulate
aspect ; Sp., spaces in trophoblast.

These appearances indicate an erosion and absorption of the maternal
tissue. The deciduofracts are probably derived from the maternal
trophospongia (Hubrecht :). After a short life-history they dwindle
and are themselves absorbed.

With the changes in the mucosa, changes also take place in the
trophoblast. After the thinning already mentioned, its cells increase
in number. They grow in strands, leaving spaces between them like
the meshes of a net, and in the spaces maternal blood circulates. In
this respect the hedgehog differs from the Eodents, in which the

1 Hubrecht now consider that the deciduofracts are of foetal origin, and
represent the outermost layer of the trophoblast. See p. 496, footnote. Also
compare Graf v. Spee's description of the trophoblast of the guinea-pig (see
p. 473), and Bryce and Teacher's of that of man (see p. 496).

480 THE PHYSIOLOGY OF REPRODUCTION

proliferation of the trophoblast is confined to the allantoic region.
In the hedgehog the proliferation occurs even in the omphaloideaii
region, which is vascularised by the area vasculosa. .Here the
vacuolated trophoblast is gradually interlocked with vascular
processes of the mesoblast, and yolk-villi, containing branches of the
vitelline vessels, are developed. The omphaloidean placenta thus
formed embraces about one-half of the circumference of the

FIG. 141. — Transverse section through the uterus of Sorex at a stage when
the blastocysts are still in the oviducts. The coiled uterine glands (Gl.)
are massed together in the anti-mesometrial regions. The uterine lumen
( U) is more or less J_-shaped. (From Hubrecht's " The Placentation of
the Shrew," Quar. Jour. Micr. Science, vol. xxxv., 1894.)

B. V., Blood-vessels ; c.m., circular muscle ; l.m., longitudinal muscle.

blastodermic vesicle. With the union of the allantois and diplo-
trophoblast, the circulation in the decidua reflexa decreases, and it
and the trophoblast in contact with it become membranaceous.
They project into the uterine cavity and obliterate its lumen by
meeting, but not fusing with, the mesometrial part of the uterine
mucosa. As in the bat, the circulation in the yolk-sac never ceases
entirely during pregnancy.

The changes in the allantoidean trophoblast are of the same kind,
but they occur later. It occupies a discoid area as in Rodents, but
it is on the anti-mesometrial side, i.e. the primary decidua reflexa is

FOETAL NUTRITION: THE PLACENTA 481

permanent. The lacimar spaces in it are more complicated than in
the omphaloidean trophoblast, and their walls bulge towards the
embryo and interlock with vascular projections of the allantois.
Hence the villi have a complete trophoblastic covering. The
extremity of each villus is attached to the maternal decidua by
strands of trophoblastic cells. The allantoidean trophospongia
develops like the omphaloidean, but it retains its thickness later
in pregnancy. The deciduofracts remain distinct to the end, though
they partly degenerate. Hence it is probable that during the whole,
or nearly the whole, of pregnancy they exercise a phagocytic action
on the maternal tissues, and store nutriment which they give up to
the embryo in a way as yet unknown.

Shrew.— In the shrew (Hubrecht l) the method of embedding is
centric, and no decidua reflexa is formed. The yolk-sac placenta
is not so well developed as in the hedgehog.

The attachment of the blastocyst is modified, as in Euminants,
by special characteristics of the uterine mucosa. They differ from
the cotyledonary burrs, however, in being proliferations of the surface
epithelium. Before the fertilised ova reach the uterus, there are
variations in thickness in the mucosa. It is thin at the mesometrial
and anti-mesometrial sections, but thickened over the sides to form
two cushions, in which the blood-vessels are more numerous. No
glands are present near the mesometrium. They are collected 011
the opposite surface and open into a longitudinal anti-mesometrial
groove (Fig. 141).

When the blastocysts reach the uterus, further changes take
place. Both the lateral regions increase in thickness by the pro-
liferation of connective tissue cells and the formation of new vessels,
while the anti-mesometrial part is widened out into a concave
bell-shaped surface into which the glands open. Then the epithelium
proliferates, first in the lateral cushions and later in the concave
area. In the former the proliferation reaches a thickness of twelve
to eighteen cells, and the new elements pass in among the cells and
vessels of the deeper layers. In the allantoidean region, the bell-
shaped area, the proliferation also leads to a thick epithelial layer
with vascular .channels between the cells. At intervals, however,
the cells are arranged radially like a fan, and later the internal parts
of the cells break away and leave a crypt. No crypts are formed in
the lateral cushions (Fig. 142).

Over the special areas of the mucosa the trophoblast thickens.
It comes in contact first with the lateral cushions by a zonary strip
against which the vessels of the area vasculosa spread out. The

1 Hubrecht, " The Placentation of the Shrew," Quar. Jour. Micr. Science, vol.
xxxv., 1894.

16

482

THE PHYSIOLOGY OF REPRODUCTION

cell-outlines in the epithelium of the cushions are lost, and a
syinplasma is formed. At the same time the trophoblast becomes
syncytial, is fused to the uterine symplasma, and absorbs part of it.
Some of the intercellular channels are opened, and the maternal
blood thus begins to circulate in the syncytial lacuna1. At the same
time a deeper cell layer, corresponding to the cytoblast of the bat,
appears in the trophoblast, but it is never so well marked as in the
allantoidean region. In this way the avillous yolk-sac placenta is
formed (see also p. 424), and it functions for a time. Soon retrogres-
sive changes appear, resulting in the absorption of the omphaloidean
syncytium and epithelium thickenings (Fig. 143). The disappearance

U.S.

FIG. 142. — Part of the anti-mesometrial wall of the uterus of Sore.? (Hubrecht).
The proliferated epithelium is arranged in a radial fashion, and later it
forms a secondary crypt (Or.), when the uterine epithelium (U.E.) gives
way over it.

is apparently brought about by a newly formed annular proliferation
of the trophoblast above the non-placental part, and the degenerated
products of the thickened uterine epithelium and of a blood
extravasate, which constantly exists between the annulus and the
epithelium, are absorbed and transmitted through the hypoblast to
the yolk-sac. From it the vessels of the area vasculosa, which at
this time reach their full development, carry the nutriment to the
developing embryo.

The allantoidean trophoblast is applied against the bell-shaped
proliferation on the anti-mesometrial side of the uterus, and is fixed
by projections which sink into the newly formed crypts. After
destroying their epithelial lining, the projections erode capillaries,
and the maternal blood circulates in the syncytial lacunse as in the
omphaloidean trophoblast. The cytoblast follows the plasmodial
projections, and later the trophoblastic villi are vascularised by the

FCETAL NUTRITION: THE PLACENTA

483

allantoic vessels. Subsequently the plasmodiblast thickens to a
considerable extent, and in it the mesoblastic villi continue to branch
and form secondary and tertiary villi. There is no penetration on
their part into the decidual tissue between the crypts, but the

ai

np

FIG. 143. — Uterus and embryo of Svrex (Hubrecht).

a.T., Allantoidean trophoblast with knobs entering the epithelial crypts (Cr.) ;
am., amnion ; all., free knob projecting into the extra-embryonic ccelom
CE.ec.) ; a.v., area vasculosa ; an', embryonic cells which grow downwards
from the upper rim of the trophoblastic annulus (tr.an.\ and adhere
against the maternal tissue ; np.T., non-placental trophoblast ; Gl.,
glands ; J/., mesometrium.

maternal part of the placenta as a whole is gradually absorbed by
the plasmodiblast, and is replaced by fostal elements. In the ripe
placenta the only maternal constituent is blood, except a thin discoid
sheet of nuclear remnants next the muscularis. The glands are not
penetrated by vascular villi. In the early stages they are plugged
by syncytium and later disappear.

484 THE PHYSIOLOGY OF REPRODUCTION

Mole. — The method of embedding is centric. A simple yolk-sac
placenta exists for a time. The allantoic placenta is discoid and is
placed anti-mesometrially. The glandular secretion is of importance
for the nourishment of the developing foetus during the greater part
of pregnancy (Strahl,1 Vernhout 2).

At the beginning of pregnancy the mucosa shows variations in its
different parts. Near the mesometrium, for about one-third of the
circumference of the lumen, the glandular layer is thin. Anti-
mesometrially the muscular layer is not so well developed, but
superficially to the glands there is a proliferation of connective tissue
cells, through which the ducts run to open into the lumen. The first
attachment is in this region.

The uterine horns show a series of small swellings where the ova
are present. The blastocysts grow to a comparatively large size, and
completely fill up the lumen. By their further growth, the epithelium
near the mesometrium is flattened and replaced by trophoblastic cells,
which do not penetrate into the connective tissue or form villi.
Hence the yolk-sac placenta is of a simple type ; it persists through-
out pregnancy.

On the opposite side the decidual formation proceeds, and the
mucosa becomes thicker. In its substance a rich network of blood-
capillaries is developed. The epithelial cells lose their boundaries
and form a symplasma. According to Strahl this remains, and forms
the syncytial covering of the future villi, but Vernhout has shown
that the trophoblast proliferates and forms a layer of epithelioid cells
which penetrate into the epithelium and absorb and gradually replace
it. Over each gland opening the trophoblast forms a dome as in
Ruminants (Fig. 144). In the placental. region the glandular
epithelium is not changed, and around each opening a small area of
the surrounding uterine epithelium persists. In the cavity between
a gland orifice and its trophoblastic cap lies a dark secretion, pigmented
by admixture with extravasated blood, and the cap is similarly
pigmented. Hence the secretion is probably absorbed by the foetal
ectoderm throughout the greater part of pregnancy during which the
glands remain. After the disappearance of the surface epithelium
at the point of connection with the blastocyst, the plasmodiblast
penetrates into the connective tissue layer which forms a symplasma.
It is followed by the cytoblast and the allantoic villi. In the
syncytium the circulating maternal blood provides for the exchange
of gases, and supplements the nutriment supplied by the glandular
secretion.

1 Strahl, " Ueber den Bau der Placenta von Talpa europea" Anat. Anz., vol. v.,
1890.

2 Vernhout, "Ueber die Placenta des Maulwurfs," Anat. ffefte, vol. v., 1894.

FCETAL NUTRITION: THE PLACENTA

485

Tupaia. — In Tupaia javanica also the placentatioii is modified by
the characteristics of the uterine mucosa. Hubrecht 1 has shown that
two specialised areas, the " Haftflecke," exist before the attachment
of the trophoblast. They lie one on each side, about midway between

m

FIG. 144. — Orifice of a uterine gland of the mole with trophoblastic dome.
(From Vernhout's "Ueber die Placenta des Maulwurfs," Anat. Heft<\
vol. v., 1894.)

m., Uterine mucous membrane ; ue., uterine epithelium ; pL, plasmodiblast ;
ci/., cvtoblast ; y.s., gland secretion.

the mesometrial and anti-mesometrial regions, and are recognised by
the absence of glandular ducts. The deeper parts of the glands
persist till the end of pregnancy, but none open on the modified areas.
The uterine epithelium again disappears at the points of contact
with the blastocyst over the " Haftflecke." There the trophoblast
becomes thickened, and its cells enlarge and penetrate between the
epithelial cells, which fuse to form a symplasnia. This is quickly
absorbed by the trophoblast, which continues to thicken, and now

1 Hubrecht, " Ueber die Entwicklung der Placenta von Tarsius und Tupaja"
Internal. Congr. of ZooL, Cambridge, 1898.

486

THE PHYSIOLOGY OF REPRODUCTION

shows two layers, plasmodiblast and cytoblast. The outer relay fuses
so closely with the decidual tissue as to be indistinguishable from it.
The capillaries dilate and new vessels are formed, especially in the
layers next the ovum. When their endotheliuin is destroyed,
maternal blood enters the trophoblastic lacunae and soon circulates
through them. The inter- vascular connective tissue cells proliferate
and form the trophospongia. The decidual layers outside it become
fibrillar, and soon are extremely attenuated. The trophospongia
remains longer, but finally it also thins, and at the end of pregnancy
there is only a thin rim of maternal tissue left.

Over the "Haftflecke" the trophoblast is first vascularised by the

All.

FIG. 145. — Replacement of omphaloidean by allantoidean placenta in Tupaia.
(From Hubrecht's " Ueber die Entwicklung der Placenta von Tarsim und
Tupaja" Internat. Congr. <>f ZooL, Cambridge, 1898.)

m.v.) Mesodermic villi ; TV., trophoblast ; TV/., trophospongia ; All., allantois ;

//.s., yolk-sac.

vitelline vessels, and a temporary yolk-sac placenta is formed. Later
the allantois displaces the yolk-sac, and its vessels vascularise the
same part of the trophoblast (Fig. 145). " The permanent placenta
replaces the omphalic placenta both physiologically and topographi-
cally " (Hubrecht). In this respect Tupaia differs from the hedgehog
and the shrew.

Centetes. — A peculiar form of placentation has been described by
Strahl1 in the tenrec (Centetes ecaudatus). A large effusion of maternal
blood destroys the centre of the allantoic placenta, and leaves only
a peripheral ring. Round the margin of the ring runs a deep groove

1 Strahl, "Beitrage zur vergleichenden Anatomic der Placenta," Abk.
enberg. Naturf.-Ges., 1905. See also Rolleston, "On the Placental Structures of
the Tenrec (Centetes ecaudatm), etc.," Trans. Zool. *S'oc., London, vol. v., 1863.

FCETAL NUTRITION: THE PLACENTA 487

which is crossed by branches of the allantoic vessels to reach an
epithelial ridge of cells.

CHEIKOPTEKA. — The mode of embedding in the bat is centric, and
the allantoic placenta is discoid. Before segmentation is completed,
the fertilised ovum reaches the uterus and invariably enters the right
cornu (Ercolani *). The zona pellucida is already thinned and soon
disappears, the spherical blastodermic vesicle lying free in the uterine
cavity.

At the beginning of gestation, according to van Beneden,2 the
mucosa is composed of a richly cellular connective tissue, covered by
a non-ciliated epithelium. Of the glands some are simple tubes, and
others divide dichotomously. None open on the mesometrial aspect
where the blastocyst later becomes fixed. There also the cellular
tissue is not so thick.

Before fixation of the blastocyst, important changes occur in the
mucosa. The sub-epithelial connective tissue cells proliferate and
form a distinct compact zone. All the capillaries dilate, even before
the disappearance of the zona pellucida, and give off many new
branches. The tissue fluids are increased, and a- serous fluid is
transuded and forms, with the glandular secretion, a coagulum around
the ovum (Van der Stricht 3).

On the mesometrial side, the trophoblast thickens around the
formative cell mass, and absorbs the surface epithelium. At the
opposite pole the cells are flattened, and they also disappear.
The fostal ectoderm, which thus conies in contact with the con-
nective tissue, is composed of two layers at the embryonic pole,
the plasmodiblast, and, internally to it, the cytoblast. At the non-
embryonic or anti-mesometrial pole the plasmodiblast is absent.

The decidua also differs at the two poles. Opposite the non-
embryonic pole the cells remain epithelioid and undergo little change.
Where they come in contact with the trophoblast, they show a
tendency to necrose. At the placental pole the deeper layers are
also composed of epithelioid cells, but superficially the capillaries
continue to dilate and make the layer spongy. The cells between
them are in active division, but next the plasmodiblast they
degenerate. This layer forms the couche paraplacentaire of Nolf4
(Fig. 146). At the placental margin it thins out and disappears.

1 Ercolani, " Nuove ricerehe sulla placenta nei pesci cartilaginosi e nei mam-
miferi," Mem. delV Accad. d. Sc. dell' Institut. di Bologna, vol. x., 1879.

- V. Beneden, " De la formation et de la constitution du placenta chez le
murin," Comp. Rend, de la Soc. de Biol., vol. v., 1888.

:! Van der Stricht, " La fixation de 1'ceuf du chauve-souris a 1'interieur de
Fut6rus," Verfi. d. anat. (resell., 13 Yers., Tubingen, 1899.

4 Nolf, " Etude des modifications de la muqueuse uterine pendant la gestation
chez le murin," Arch, de Biol., vol. xiv., 1896.

THE PHYSIOLOGY OF REPRODUCTION

Beneath the epithelioid layer in both areas the cells are drawn out
and pseudo-fibrous. The conditions for nutrition resemble those in
the very early human ovum, the trophoblast lying against a non-
vascular detritus-zone. But in the bat there is strong evidence of
phagocytosis. The epiblastic protoplasm, where it is in contact with

VdaU

FIG. 146. — The placenta of the bat. (From Nolf's "Etude des modifications de
la ruuqueuse uterine pendant la gestation chez le murin," Arch, de JJiol.,
vol. xiv., 1896.)

m., Muscularis ; a., unaltered mucosa ; C.ep., epithelial layer ; gl., glands ;

O.pp., paraplacental layer with blood-spaces (b) ; Art., artery running

, towards trophoblast ; !>., vein ; TV., trophoblast with lacunae ; Vil. all.,
allantoic villi.

dead tissue, is " crammed with irregular granules, some fatty and
others coloured brown with safranin " (Xolf). The mouths of the
glands opening at the non-embryonic pole are filled with debris, and
their epithelium is degenerated and desquamated. As previously
mentioned, no gland-ducts are present in the conche paraplacentaire.
The blind ends of the glands are, however, distended with secretion,
and their epithelium is normal.

Next a change occurs such as Hubrecht described in the hedgehog
(see p. 478). The endothelium of some of the vessels in the para-

FCETAL NUTRITION: THE PLACENTA 489

placental layer proliferates irregularly round the lumen, and
degenerates. In the bat, according to Noli, the vessels in which
the change occurs are the venous capillaries, in which the blood,
returning from the placenta charged with foetal excretory products,
stagnates and produces the hyperplasia and simultaneous degenera-
tion. Hubrecht, however, states that an endothelial proliferation
occurs in arterial and venous capillaries alike in the hedgehog.

At the embryonic pole the plasmodiblast undergoes a marked
thickening. It gradually replaces the superficial decidual cells,
and surrounds the vessels as in the rabbit. Then it attacks the
endothelial sheath and replaces it, so that lacunre of maternal blood
come to be surrounded by foetal tissue. At the same time the
cytoblast sends out cellular buds, which project into the plasmodial
mass. Under the cytoblast is the double layer of mesoblast, the
thin somatopleur, and the splanchnopleur in which the area
vasculosa is developed. A yolk-sac placenta is thus formed in
the same region as is subsequently occupied by the allantoic
placenta. Nutritive exchanges between maternal and foetal blood
are now possible.

In the further development of the placenta there is very little
or no penetration of maternal tissue by the trophoblast (Duval1).
Degenerative changes occur in the cells of the epithelioid layer in
the placental hemisphere. They lose their outlines, and form a
symplasma which is absorbed by the adjacent cells of the couche
paraplacentaire (Xolf). Superficially the paraplacental layer remains
until the end of pregnancy. The blind ends of the glands are still
distended, but their epithelium degenerates and is cast off into
the lumen.

In the non-placental trophoblast, retrogressive changes also occur.
Its cells lose their phagocytic power and contain no granules. In
the placental area, as already mentioned, the allantois replaces the
yolk-sac. The " villi " resemble the tubes of the rabbit. They form
a series of arches whose meshes are occupied by allantoic vessels ;
there are no villi hanging free. As the placenta develops, the
thickness of the arches surrounding maternal blood is reduced, and
the two blood-streams lie close together. The cytoblast almost
entirely disappears.

Pteropus edulis. — In Pteropus the placenta is attached to a large
mushroom-shaped outgrowth of the uterine wall which grows nearly
round the ovum to form a decidua capsularis. As pregnancy advances,
the outer wall of the bell-shaped decidual mass is pressed against the

1 Duval, "Etude sur 1'embryologie des Cheiroptkres," Jour, de VAnat. et de la
Phys., 1895-97.

16 A

490 THE PHYSIOLOGY OF REPRODUCTION

uterine surface and fuses with it. In this way the completed placenta
is discoid (Gohre 1).

PRIMATES. — The order of the Primates includes monkeys, apes,
and rnan. Hubrecht and Jenkinson also include Tarsivs, a lemur
(see p. 440). Owing to the difficulties of securing material for
investigation, many details regarding the early stages of development
of the foetal membranes and placenta are yet unknown.

From the researches of Turner, it is known that the placentation
is in general the same throughout the order, except for differences in
the size and form of the villi, and in the structure of the decidua.
On the other hand, the Primates are distinguished from all other
placental Mammals in that they do not form an allantoic placenta.
Notwithstanding the variations in the degree of its development, in
all the orders previously considered the allantois projected fre*e into
the extra-embryonic coalom before it was united with the wall of the
blastodermic vesicle. In the Primates and Tarsius the embryo is
attached from the beginning to the wall of the blastocyst by the
" Bauchstiel " or " Haftstiel," a mesodermal connecting-stalk first
observed by His2 in human embryos. The allantois appears very
early as a recess of the posterior wall of the yolk-sac before the
formation of the hind-gut. It never projects free into the coelom,
but is contained as a narrow tube in the " Bauchstiel " without
reaching at any time the wrall of the blastocyst (Fig. 147). The
trophoblast is in this way vascularised directly, and a chorionic
instead of an allantoic placenta is formed. For this reason Hubrecht
has suggested that the term chorion should be restricted to the
Primates. Minot3 strongly supported the views of His. He went
even further, and stated that the placenta was also chorionic in
Carnivora, Eodentia, Insectivora, and Cheiroptera, but his views have
not been generally accepted. Regarding the modification in Primates,

1 Gohre, " Dottersack und Placenta des Kalong (l't'/i-<>f><i>> edulu}" Stndien
iiber Entwicklungsgeschichte der Thiere, Selenka, vol. v., 1892. The formation of
the amnion in bats has recently been investigated by Da Costa (" Sur la forma-
tion de 1'amnios chez les Cheiropteres (Miniopterus schreibersii} et, en general,
chez les Marnmiferes," Mem. Soc. Portugaise des Sci. J'at., Porto, 1920). He
describes three phases : (1) The appearance of a closed cavity in the embryonic
disc, the upper wall of which is the primordial amnion ; (2) the rupture of this
wall and the disappearance of the primordial arnniotic cavity, which is replaced
by a tropho-ectoblastic space ; (3) the formation of an amnion and a definitive
amniotic cavity with ectoblastic folds. In some other bats, Mvriiivs and the
Noctule, it is the same, except that the primordial amniotic cavity is less definite.
Primordial amniogenesis of the same type is seen in the guinea-pig, Gad -<y </>/«'< -n*
Tatusia, and in Primates. The primitive cavity disappears and is replaced by
a cavity which is limited by the amniotic folds in Microcheiroptera, the pig,
mouse, etc. The primitive cavity may be absent or only hinted at, as in the
hedgehog, mole, rabbit, etc., Tarsius, Carnivora (see above, p. 412).

2 His, Anatomii' ,,/>', /«<•/,/ ,',•/,/-,• Embryo/Ren, I.

3 Minot, Human Embryology, Boston, 1892.

FCETAL NUTRITION: THE PLACENTA

491

Hubrecht 1 says : " Once the embryonic circulation has found the
shortest route towards the trophoblast by way of the ' ventral stalk,'
trophoblastic lacunse, with their profusion of maternal blood, which
have been there from the very earliest periods of development, are
exquisitely situated for rendering this new adaptation highly
advantageous. And while in the ancestral forms of the Primates
both yolk-sac and allantois largely drew upon the trophoblastic
source, these embryonic organs come to be dispensed with to a very
great extent in their more highly developed descendants who come to
use that trophoblastic source along a more direct, a shorter, and an
earlier established route."

In old-world monkeys there is no decidua capsularis. The

FIG. 147. — Median longitudinal section of an early human ovum, 0'4 mm. in
length. (From Quain's Anatomy, Longmans.)

e.ec.j Embryonic ectoderm ; c/i., chorion ; ec., ectoderm ; mes., mesoderm ;
all., allantois ; c.s., connecting stalk ; «., amnion ; y.s., yolk-sac.

trophoblast thickens over two discoid areas on the blastocyst, and
the thickenings form a primary placenta on the dorsal surface, and a
smaller secondary placenta on the opposite aspect. Hence two groups
of chorionic villi are developed.

No unattached blastocyst has yet been obtained. In the youngest
specimen of an old-world monkey, Semnopithecus nasims, the ovum
was attached to the surface of the uterus by large -villous processes
with mesoblastic cores at the bases. The trophoblast consisted of
two layers, the cytoblast, which was much thickened at the tips
of the mesoblastic cores, and, externally to it, a syncytium which was
blended at the apices with maternal decidua. Over the non-villous
chorion syncytium was absent (Selenka). Spaces, which are in
direct communication with maternal capillaries, are present in the
syncytium. The most notable characteristic in the decidua is
the presence of a glandular secretion in the embryotrophe. In the

1 See Robinson's Hunterian Lectures, Journ. of Anat. and Phys., vol.
xxxviii., 1904.

492 THE PHYSIOLOGY OF REPRODUCTION

non-placental area the glands are dilated and open into the uterine
cavity, many of them close to the peripheral villi. Hence their
secretion may reach the trophoblastic lacume. In the placental
region they are also dilated, but their superficial parts are closed and
appear to degenerate early. In the decidua lie nests of epithelioid
cells, the origin of which is uncertain.

The new-world monkeys, like the old-world, have no decidua
capsularis, and the placenta is formed as a single disc. In the
anthropoid apes, on the other hand, the ovum is lodged in an
implantation cavity, and so is covered by a reflexa. The whole
circumference of the trophoblast thickens and develops villi, but
later they disappear except over a discoid area, the decidua serotina.
In the earlier stages two main groups of villi are present as in the
old-world monkeys, while the rest of the chorion is covered with
smaller villi.

In Selenka's youngest specimen, the ovum was completely
enclosed by decidual tissue, and there was no evidence to show
whether the mode of embedding was excentric or interstitial. The
surface of the ovum was separated from the decidua by a series of
intercommunicating spaces, the intervillous spaces, which contained
lymph. In other words, Selenka looks on the intervillous space in
apes as a space lying between maternal and foetal tissues, in which
villi are suspended.

In man also the villi are at first diffuse, and later restricted to a
discoid area, the placenta being again developed in the decidua
serotina.

The ovum probably reaches the uterus still enclosed in the zona
pellucida, and lies free until the end of the first week, but this stage
has never been observed. The uterine mucosa, as in other orders, is
matured about the time of puberty (Bjorkenheim l), and then
consists of embryonic connective tissue cells, separated from the
surface epithelium by a layer of flattened cells. The intercellular
spaces are filled with lymph, and they drain into lymphatic vessels
in the outer half- of the mucosa, where also the arterioles and venules
lie. All the blood-vessels in the inner half are capillaries. In all
probability the fertilised ovum, during its sojourn in the Fallopian
tube and while it lies free in the uterine cavity, does not influence
the structure of the mucosa, and may implant itself at any period
during the oestrous cycle (Bryce and Teacher2). But under the
abnormal conditions in a tubal pregnancy, the uterine mucosa under-
goes a decidual change although no fertilised ovum is embedded in it.

1 Bjorkenheim, "Zur Kenntnis der Schleimhaut im Uterovaginalkanal des
Weibes in den verschiedenen Altersperioden," Anat. Hefte, H. cv., 1907.

2 Bryce and Teacher, The Early Imbedding and Development of the Human
Ovum, Glasgow, 1908.

FCETAL NUTRITION: THE PLACENTA 493

In all the early specimens the ovum was completely enclosed in
the uterine mucosa, and the actual process of embedding has not
yet been observed. John Hunter considered that the ovum reached
the uterus from the Fallopian tube under the mucous membrane,
and so had a decidua reflexa, while at a later stage the mucosa
developed underneath it ; hence the term decidua serotina. Sharpey
supposed that the enclosure was effected by circumvallation, i.e.
by a growth round the ovum of two folds of mucosal tissue, which
fused and formed the decidua capsularis. But v. Spee 1 discovered a
different mode of embedding in the guinea-pig, and later stated that
it was the same in man, viz. a destruction of the superficial epithelium,
and the 'implantation of the ovum in the cellular substance of the
mucous membrane. This view has received considerable support
from the researches of v. Heukelom,2 Peters,3 Bryce and Teacher, and
others. At the same time it must be borne in mind that His,4
in describing an early human ovum in 1897, stated that the
implantation cavity was lined with epithelium,5 and thus represented
a part of the uterine lumen shut off by the growth of decidual folds.

At the time of embedding, segmentation has probably finished
and the ovum is in the condition of the early blastocyst. Its
epiblastic wall disintegrates the epithelium, the subjacent cells, and a
few capillaries at the point of contact. Hence the blastocyst comes
to lie in the connective tissue of the mucosa, which completely
surrounds it, except at the point of entrance of the ovum. Here
there is a gap in the tissue, the " G-ewebspilz," filled up at first by a
blood-clot which afterwards becomes fibrinous (Peters), and later by
decidual tissue (Kollmami 6). In Peters' ovum the gap was four-
fifths of a millimetre in diameter, and in Bryce and Teacher's a tenth
of a millimetre. The size of the ovum when it becomes embedded
is probably, according to the last-named authors, a fifth of a
millimetre.

When the hypoblast of the early blastocyst is differentiated, it
does not apparently line the wall of the blastocyst, but forms a small
vesicle. Very early, even before the appearance of the primitive
streak, a marked proliferation of mesoblast occurs (Fig. 148). In
the youngest ovum its cells filled the space between the wall of the

1 V. Spee, " Neue Beobachtungen iiber sehr friihe Entwicklungsstufen des
menschlichen Eies," Arch. f. Anat. u. P/iys., Anat. Abth:, 1896.

2 V. Heukelom, "Ueber die menschliche Placentation," Arch. f. Anat. u. Phys.,
Anat. Abth., 1898.

3 Peters, Ueber die Einbettunq des menschlichen Eies, Leipzig u. Wien, 1899.

4 His, " Die Umschliessung des menschlichen Frucht wahrend der friihesten
Zeit der Schwangerschaft," Arch.f. Anat. u. P/n/s., Anat. Abth, 1897.

5 Cf. Johnstone, " Contribution to the Study of the Early Human Ovum,"
Jour, of Obstetrics and Gyncecology, (May) 1914.

0 Kollmann, "Die menschlichen Eier von 6 Millimeter Grosse," Arc/i. f.
Anat. u. P/it/s., Anat. Abth., 1879.

494 THE PHYSIOLOGY OF REPRODUCTION

blastocyst and the small amniotic and hypoblastie vesicles. In the
ovum described by Leopold,1 it was already split by the " Haftstiel "
into two parts, which enclosed the coalom and were continuous with
each other (Fig. 149). The outer wall of the blastocyst, the foetal
ectoderm or trophoblast which anchors the ovum in the mucosa, is

--

thickened all round its circumference/ and even in the earliest
specimen contained vacuoles into some of which maternal blood had
penetrated. In this thick spongy layer Bryce and Teacher found no
cell-outlines anywhere. Hence the transformation to syncytium is not
due, as Peters supposed, to the contact with maternal blood. Under
the syncytium is the cellular layer, corresponding to the cytoblast of

1 Leopold, " Demonstration eines sehr jungen menschlichen Eies," Arbeitcn
aus d. Kmiigl. FrauenMinik in Dresden, Leipzig, 1906.

FCETAL NUTRITION: THE PLACENTA

495

Beneden. Its cells are in a state of active division, and they appear
later to lose their outlines and merge into the syncytium. The
growth of the latter from the mother-zone of cytoblast occurs, not

as a solid mass, but in strands forming primitive syncytial villi
(Fig. 150). Into the syncytium project outgrowths of the cytoblast,
forming the cellular villi of Peters and Leopold. In the youngest
ovum the formation of these buds was just commencing, and, according
to Bryce and Teacher, they tended to grow out not so much into the

496

THE PHYSIOLOGY OF REPRODUCTION

strands of trophoblast as into the spaces between them. Later still,
mesoblastic processes penetrate into the cellular buds and complete
the vascular chorionic villi.

Round the blastodermic vesicle is a zone of degenerated tissue,
the " Detrituszone " (Fig. 151). It is uncertain whether it is formed

Cft

dec

FIG. 150. — Section of a portion of the wall of the human blastocyst.
(Bryce and Teacher.)

cy£., Cyto-trophoblast ; dec., decidua ; end., endothelium of maternal capillary ;
pi., plasmodium ; nz^ necrotic zone of decidua.

«
by the influence of the trophoblast or maternal elements. At its

inner edge, and within its spaces, are numerous large mononuclear
cells which are " more likely maternal " (Bryce and Teacher). Peters
also mentioned the presence of man}1" large cells, and compared them
to the deciduofracts of the hedgehog. V. Heukelom described the
cellular layer outside -the syncytium as foetal, and derived from
Langhans' layer.1 Whatever their origin, the mononuclear cells in

1 Much uncertainty still exists regarding the origin of these large cells in
man and other animals. In the mouse, Duval and Sobotta consider them foetal,

FCETAL NUTRITION: THE PLACENTA 497

man appear to be engaged in disintegrating mucosal tissue, and
producing a zone of coagulation necrosis, i.e. a symplasma, around the
trophoblast. But they differ from similarly situated cells in lower
animals, e.g. the mouse, in showing no evidence of ingestion of formed
tissue-elements.

In the youngest ova no space exists between the trophoblast and
the wall of the implantation cavity (Fig. 152). In later specimens
a space is formed, apparently by the absorption of the debris of the

FIG. 151. — Section of a portion of the necrotic zone of the decidua, and of
the layer of large cells on its inner aspect. (Bryce and Teacher.)

nz., Necrotic zone ; me., large cells in various stages of degeneration ;
car., blood-filled implantation cavity.

necrotic zone. How this excavation is brought about is uncertain.
According to Peters, the trophoblast may exercise a phagocytic
action. Bryce and Teacher, however, found no evidence of such "a
process, and inclined to the opinion that the material was dissolved
by an enzyme before its absorption. In the trophoblast they found

Kolster and Disse maternal, and Jenkinson both foetal and maternal. In the

fuinea-pig, v. Spee states that they are foetal. In the hedgehog they were
rst described by Hubrecht as maternal, and later as foatal. In man, as stated
above, the same doubt exists whether the trophoblast consists of two layers,
cytoblast and plasmodiblast, or possesses a third layer composed of large cells,
and forming the advance guard in attacking the uterine mucous membrane and
enlarging the " Eikammer."

X

498 THE PHYSIOLOGY OF REPRODUCTION

that some of the vacuoles were not yet filled with maternal blood,
but contained a granular coagulum which might, when liberated,
have a digestive activity. In either case, the extensive proliferation
of the trophoblast appears to provide for the absorption of the
necrosed tissue around it, as well as for the flow of maternal blood
into its lacuna^ by the erosion of superficial capillaries. These two
objects accomplished, the greater part of the trophoblastic prolifera-
tion disappears.

Sp.-

FIG. 152. — Section through embryonic region of ovum (after Peters).
(From C. Webster's Human Placentation.)

E.Sch., Embryonic epiblast ; Ent., embryonic hypoblast ; Mes., niesoblast ;
D.S.j umbilical vesicle ; A.H., amniotic cavity ; Ekt., chorionic epiblast ;
#/>., space.

Immediately after the excavation of the cavity the decidual
formation begins. Before this stage, the changes resemble those
that take place during the menstrual period. The vessels are dilated,
and blood extravasations occur between the cells and into the lumen.
The tissue is cedematous and spongy, and the swollen cells often
appear to be floating free in a fluid (v. Heukelom). These changes
are especially marked near the ovum, and they give rise to an
elevation which marks the resting-place of an early blastocyst. The
mucosa is differentiated into a superficial layer, the compacfa, and a
deeper layer, the spongiosa, in which are the enlarged middle portions
of the glands, arterioles, venules, and lymphatics. In the compacta

FCETAL NUTRITION: THE PLACENTA

499

the connective tissue cells undergo active
division, and they enlarge to form the
decidual cells (Fig. 153). Before the exca-
vation of the "Eikammer" they are prob-
ably not found, though Peters described
the commencement of a decidual change
before that stage. In Merttens'1 ovum
large decidual cells were found, many of
them fusiform and lying parallel to the
surface. The decidual change arises first in
the connective tissue cells near the ovum,
and later it extends more deeply in the
compacta. There is no special perivascular
development as in the rabbit, and no endo-
thelial proliferation as in the hedgehog and
bat, though the latter may occasionally occur
in tubal pregnancy (Webster 2).

The capillaries dilate to sinuses, and new
vessels are also formed in the compacta.
Many of them are opened by the trophoblast
and perhaps by the mononuclear cells, and
gradually more and more blood is effused
into the trophoblastic lacuna?. In them it
does not clot, the syncytium acting as an
endothelium, but at a certain stage the
blood begins to circulate and continues to
do so throughout pregnancy. The gland-
ducts are destroyed in the necrotic zone.
In the underlying compact zone they are
found dilated in the serotiiia and base of the
reflex'a, but even in Bryce and Teacher's
ovum the epithelium showed signs of de-
generation and desquamation.

With the formation of the space between
the ovum and the decidua, a permanent
attachment of the two structures is brought
about. The development- of the villi has

1 Merttens, " Beitrage zur normalen und patho-
logischen Anatomic der menschlichen Placenta,"
Zeitsch. f. freburtsh. u. Gyniik., vols. xxx. and xxxi.,
1894-95'.

2 Webster, Human Placentaticm, Chicago, 1901.
Wade and Watson (Jour, of Obstet. and Gynec. of
Brit. Emp., 1908) also state that in tubal pregnancy
some of the decidual cells are formed from endo-
thelium.

FIG. 153.— Condition of
the glands at the be-
ginning of pregnancy
in man (after Kundrat
and Engelmann).
(From Quairis An-
atomy, Longmans.)

<•, Compact layer near
free surface of de-
cidua : the glands are
here somewhat en-
larged, but not very
tortuous, and the
mucous membrane is
rendered compact by
the hypertrophy of
the interglandular
tissue ; sp., spongy
layer containing the
middle portion of the
glands greatly en-
larged and tortuous,
producing a spongy
condition in the
mucous membrane ;
d, deepest portion of
glands, elongated and
tortuous, but not
much enlarged ; m,
muscularis.

500 THE PHYSIOLOGY OF REPRODUCTION

already been traced up to the stage when they consisted of simple
stalks of mesoblast with a double ectodermal covering. In the
core are developed capillary vessels which are continuous with
the vessels of the " Haftstiel," and later with those of the
umbilical cord. After the excavation of the necrotic zone, some
of the stalks reach the decidual surface and attach the ovum to

Fro. 154. —Median longitudinal section of an embryo of 2 mm. (von Spec).
(From Quain's Anatomy, Longmans.)

v., Villus ; c.v., core of villus ; ines., mesoderm ; c.s., connecting stalk ; p.s.,
primitive streak ; «//., allantois ; y.s., yolk-sac ; But., entoderm ; ves.,
vessels ; /?., heart ; «./>., notochordal plate ; a., amnion.

it. At first the attached ends of these primary villi are plasmodial,
but later the cytoblast proliferates and forms thick rounded masses,
the " Zellsaulen," over which the sync'ytium disappears. This
forms the permanent attachment between the villi and the decidual
surface. The spaces between the stalks form the primary inter-
villous space, which is thus entirely in the plasmodiblast. The
primary villi form buds of their three layers which develop into
secondary villi. Of these some may also Ijecome attached to the
decidua, while others hang free in the intervillous space. By a
similar process other villi are also developed, till the whole system

FCETAL NUTRITION: THE PLACENTA 501

becomes branched like a tree (Fig. 154). At first they are equally
distributed over the chorion, but the villi in relation to the reflexa do
not branch so much, and even at the end of the first month they are
fewer in number than over the serotina (Kastschenko1). When the
blood-supply to the reflexa is reduced, the villi in relation to it
degenerate, and are compressed between the chorion and the apposed
decidua reflexa and vera. Over the serotina they continue to branch
and form the fetal part of the placenta, which is essentially a mass
of fetal villi between which maternal blood circulates. By the

sy.

FIG. 155. — Diagram of stage in the development of the human placenta.
(T. H. Bryce in Quain's Anatomy, Longmans.) The "Haftzotten" are
attached to the surface of the decidua. The mesodermic processes are
everywhere covered by a single layer of cells (Langhans' layer) and a
lamella of syncytium.

6., Attachment of a villus ; mes., mesoderm ; ves., vessels going to villi ;
sy., syncytium ; L.I., Langhans' layer ; a., cross-section of a villus ;
dec., decidua ; ca., maternal capillary.

" Haftzotten " the spongy mass is attached to the decidual surface.
The attached ends may excavate the decidua to some extent, but
there is no great degree of penetration (Fig. 155).

As pregnancy advances, marked degenerative changes occur in
the maternal and foetal parts of the placenta. The most notable
change in the villi is the gradual disappearance of the cytoblast, the
mother-zone of the syncytium. Even the " Zellsaulen " tend to
disappear from the tips of the villi, and their connective tissue
comes in contact with the decidua. Fibrinous changes are frequent
in the remnants of the cytoblast and in the mesoblast. The

1 Kastschenko, " Das menschliche Chorionepithel und dessen Rolle bei der
Histogenese des Placenta," Arch. f. Anat. u. Phys., Anat. Abth., 1885.

502 THE PHYSIOLOGY OF REPRODUCTION

syncytium becomes very thin, and occasionally tracts of it are
stripped off.

The decidua serotina, after reaching its full development during
the third month, is gradually thinned out. This may be partly due
to the stretching of the tissue by the increasing growth of the uterine
contents, but it would seem also to depend on conditions of mal-
nutrition caused by the blood-stasis (Bonnet), and the choking of
the lymphatics by the decidual development (Webster). The
resulting degeneration takes the form of a coagulation necrosis or
symplasma, as shown by the " Fibrinstreifen," which are comparable
to the fibrmous deposits in the rabbit's placenta. The layers of
fibrin in the serotina were first described by Nitabuch.1 They may
be seen as early as the sixth week, and even earlier in the reflexa
(Webster). They gradually extend more deeply into the substance
of the decidua, and also occur in the vessel walls. They are, however,
most marked 011 the surface, at or near the junction of the maternal
and foetal tissues. That they are due to the influence of the ovum
is highly probable from their absence in the vera. Whether the
symplasma is formed from the blood or the decidua, or both, is not
known. It is probably absorbed by the villous ectoderm during the
greater part of pregnancy.

According to Webster, there may be a new formation of decidual
tissue during pregnancy, from irregularly distributed groups of active
cells which are present at all periods in the maternal part of the
placenta (see p. 402).

The uterine glands take no part in the formation of the placenta.
By the sixth week their superficial parts are largely obliterated, and
the deeper parts degenerated. At a later stage, only a few blind
ends are seen next the muscular layer. Though their epithelium
offers a considerable degree of resistance, and is visible for a long
time, its secretory power is probably lost very early. According to
Gottschalk,2 the glandular epithelium undergoes a fatty degeneration,
but Bonnet 3 states that the change is a hyaline one. In the vera the
glands increase in size and secrete actively for a time. Their secretion
is found as a milky fluid in the 'uterine cavity.4

1 Nitabuch, "Beitrage zur Kenntnis der menschlichen Placenta," Inaug.-
Dissert., Bonn, 1887.

2 Gottschalk, " Weitere Studien liber die Entwicklung der menschlichen
Placenta," Arch. f. (.tyiui'L, vol. xl., 1891.

3 Bonnet, " Ueber Syncytien, etc.," Monatsschr. f. Geburtslt. v. '/y/w/-.,
vol. xviii., 1903.

4 Wislocki and Key have studied the distribution and character of mito-
chondria (which are sometimes regarded as an index of the metabolic activity
of a cell) in the mature placenta of man and other animals. It was found that
while mitochondria are present in all placental tissues (ftetal and maternal),
they are most abundant in the epithelial cells forming the barrier between
the two circulations. They are also abundant in the endothelium lining the

FCETAL NUTRITION: THE PLACENTA 503

Glycogen

Glycogen is present in the early stages of pregnancy. Langhans x
demonstrated it in the decidual cells, in the cellular proliferations of
the trophoblast at the tips of the villi, and in the mesoblast. It was
absent in the canalised fibrin and Langhans' layer. Merttens 2 also
found it in the decidua near the ovum. Driessen 3 states that it is
present in the superficial and glandular epithelium of the uterus in
the first month of pregnancy ; around the ovum " in cells of doubtful
origin " glycogen is plentiful, but absent in the deeper parts of the
decidua ; in the villi it is not found in the syncytium and Langhans'
layer, but is present in the cell-islands at the tips of the villi, and
occasionally in the mesoblast. The total amount is, however, much
smaller than in Rodents, and represents only about 0'08 per cent, by
weight (Cramer4).

Fat was first described in the human placenta by Apfelstedt and
Aschoff.5 They found it during the second month of pregnancy in
the syncytium and Langhans' layer, and in the decidual cells near
the villi. Eden0 found fat in the perinuclear protoplasm of the
syncytium, and in Langhans' layer and the stroma of the villi. It is
also present in the capillary walls (Dastre7). The appearances
suggested to Eden that "the placenta appears to be a storehouse of
nutritive fat just as is the liver." Minute discrete droplets were also
present in the decidual cells, and by the sixth month they had
increased in number. At full time the serotina still contained fat,
but " it is doubtful whether now it is a physiological deposit, as the
serotina shows many degenerative changes." At the same time, a
fatty degeneration of the decidua is probably pathological and not a
constant phenomenon (Klein8), and the fat globules in the early

maternal blood channels and in the glands of the uterine mucosa. (Wislocki
and Key, "The Distribution of Mitochondria in the Placenta," Contributions
to Embryology, vol. xiii., Carnegie Institute (Washington) Publication No. 27.6,
1921.)

1 Langhans, " Ueber Glykogen in pathologischen Neubildungen uncl den
menschlichen Eihauten," Virchotv's Arc/i., vol. cxx., 1890.

2 Merttens, " Beiti age zur normalen und pathologischen Anatomie der
menschlichen Placenta," Zeitseh. f. Geb. u. Gyw'ik., vols. xxx. and xxxi., 1894-95.

3 Driessen, " Ueber Glykogen in der Placenta," Arch. f. Gynfik., vol. Ixxxii.,
1907.

4 Cramer (A.), " Beitrage zur Kenntnis des Glykogens," Zeitsdi. f. Biol.,
vol. xxiv.

5 Apfelstedt and Aschoff, " Ueber bosartige Tumoren der Chorionzotten,"
Arch. f. Gi/nak., vol. 1., 1896.

(i Eden, "The Occurrence of Nutritive Fat in the Human Placenta," Proc.

Roy. Soc. Londan, vol. lx., ] 896.

~ See Richet's Dicttonnaire de Physiologic, vol. vi., Article " Foetus."

8 Klein, " Entwicklung und Riickbildung der Decidua," Zeitseh. f. Geburtsh.

u. Gytiak., vol. xxii.

504 THE PHYSIOLOGY OF REPRODUCTION

stages represent an infiltration of fat into the decidual cells from the
maternal blood.

From the absence of fat in the more superficial parts of the
syncytium, Hofbauer1 suggests that it may be split up into fatty
acids and glycerine before absorption, and then re-synthesised by the
foetal placenta (Fig. 156). Thence it is carried by the blood in a
soluble form, and is again deposited in droplets in the heart, liver,
lungs, alimentary tract, and spleen of the foatus. In the later months
of pregnancy there is a considerable deposit of fat in the subcutaneous
tissue.2

FIG. 156. — Fat in a villus of the human placenta. (From Hofbauer's
Biologie der menschlichen Plazenta, Braumiiller.)

fs., Fat globules in deeper layers of syncytium ; fs'., fat in syncytium between
Langhans' cells ; fb., fat in mesoblast ; fv., fat in vacuolated cell.

Lipoids

Bienenfeld 3 states that he found large quantities of lipoids in the
placenta in the earlier stages of pregnancy, but that as pregnancy
went on the lipoid content decreased. The quantity of lipoids was
exceptionally high in the condition of eclampsia.

Respiration
The respiratory exchange in the human foetus has been studied

1 Hofbauer, G'rundziige einer Biologie der menschlichen Plazenta, Leipzig, 1905
(see above, pp. 475 and 543).

2 See also Bondi, "Ueber das Fett in der Placenta," Arch.f. Gyndk., vol. xciii.,
1911 ; and Ballerini, " Histochemische Untersuchungen iiber Fettstoffe und
Lipoda im Plazentargewebe," Arch. f. Gyniik., vol. xcviii., 1912.

3 Bienenfeld, " Beitrag zur Kenntnis des Lipoidgehaltes der Placenta,"
Biochem. Zettsch., vol. xliii., 1912. See also Ballerini, loc. cit.

FCETAL NUTRITION: THE PLACENTA 505

indirectly by a number of investigators1 (if. Rodents, p. 464).
Hasselbalch 2 found tbe respiratory quotient of the new-born baby to
be unity, thus indicating carbohydrate as the source of the child's
energy. Weiss3 subsequently found the quotient to be between
•7 and '95. More recently Benedict and Talbot 4 carried out a series
of metabolism experiments on 105 newly-born infants, taking special
precautions against error. They found that the average respiratory
quotient for seventy-four babies during the first twenty-four hours
after birth was '8, thus showing that the substance oxidised could
not have consisted entirely of carbohydrate. During the first eight
hours, however, the quotient was somewhat higher. Tt tended to
fall until the third day, after which it rose, owing possibly to the
carbohydrate supplied in the mother's milk.

Iron

In man, Peters found evidence of the presence of red blood
corpuscles in the trophoblast of the early ovum, and Ulesco-
Stroganoff5 states that they are also present in the syncytium in
later stages. This has been disputed by Kworostansky ° and Hofbauer,
who maintain that the corpuscles are first dissolved. More recently
Bryce and Teacher found no evidence of the ingestion of red blood
corpuscles by the trophoblast, while Bonnet " has shown that the
syncytium gives the eosin-reaction of hienioglobin at the points where
it comes in contact with extra vasated blood. It has been stated that
placental extracts produce haemolysis in vitro (Veit and Scholten 8),
but whether a similar action takes place in the body is unknown.

Iron-containing compounds are also found in the villi. Using the
method of Hall, which demonstrates iron in loose organic compounds,
Hofbauer found none such in the superficial layers of the syncytium,
but an increasing number of granules were present in the deeper
parts. In the mesoblast they again decreased in number, and were
altogether absent near the capillary walls (Fig. 157). He suggests

1 Feldruan, Principles of Ante-Natal and Post-Natal Child Physiology, London,
1920.

2 Hasselbalch, "Respiration Experiments with New-born Infants,'' originally
published in Copenhagen, 1904 ; republished in English in Benedict and Talbot's
memoir, The Physiology of the New-born Infant, Carnegie Institute (Wash-
ington) Publication No. 233, 1915.

3 Weiss, "Les Echanges Respiratoires des Nouveaux-nes et 1'Indice
d'Oxygenation," Bull. Acad. de Med., Paris, vol. lx., 1908.

4 Benedict and Talbot, Joe. cit. This memoir contains other references.

5 Ulesco-Stroganoff, " Beitrage zur Lehre vom mikroskopischen Bau der
Placenta," Monatsschr. f. Geburts/i. u. Gyiiiik., vol. iii.

6 Kworostansky, "Ueber Anatomie und Pathologic der Placenta," Arch. f.
Gynak., vol. Ixx., 1903.

7 Bonnet, quoted by Hofbauer, loc. cit.

8 Veit and Scholten, " Synzytiolyse und Hamolyse," Zeitsch. f. Geburtsh. u.
Gynak., vol. xlix., 1903.

506

THE PHYSIOLOGY OF REPRODUCTION

that at first the haemoglobin derivatives are in too firm combination
to take on the stain, then they are further broken down and stained
granules appear, and later they are again synthesisecl into 11011-
stainable compounds which reach the foetal circulation. Such
changes were characteristic of the first half of pregnancy. In the
second half the iron-reaction of the villi was " extraordinarily slight."
Iron is stored in the liver and other fostal organs. According to
Bunge,1 it diminishes rapidly after birth, and he supposes that it

compensates for the insufficient amount of
iron contained in the mammarv secretion.

Albumen

The transmission of albumen- to the
foetus of the rabbit has already been referred
to (see p. 464). In the human placenta
attention has been chiefly directed to the
investigation of the decomposition products
of proteins. Matthes2 and Hofbauer state
that albumoses are present in the placenta,
but this is doubtful. In watery extracts
liielander 3 demonstrated purine bases, uracil
and choline, and in the autolysed placenta
leucine and tyrosine have been found
(Basso4). It is generally held that such
results prove an active metabolism of pro-
tein in the foetal placenta.

Creatin and Creatinine

Hunter and Campbell5 have investigated
the concentrations of creatin and creatinine
in the fetal and maternal blood. Their

FIG. 157.— Iron granules
in a villus of the
placenta in man.
(From Hofbauer's
Biologie der men-sch-
lichen Plazenta, Brau-
niuller.)

method was to take a sample of blood from

the placental end of the umbilical cord as soon as it was cut and at
the same time from the arm vein of the mother. They found a very
slightly higher concentration in the fetus. They conclude that the
placental transmission of creatin and creatinine is a simple process of
diffusion.

1 Bunge, " Ueber die Aufnahme des Eisens
Sauglings," Zeitsch. f. phys. Chem., vol. xvii., 1893.

in den Organismus des

2 Matthes, " Ueber Autolyse der Placenta," Centralbl. f. Gynak., 1901.

3 Rielander, "Ein Beitrag zur Chemie der Placenta," Centralbl. f.
1907.

4 Basso, " Ueber Autolyse der Placenta," Arch. f. Gtfn<ik., vol. Ixxvi.

5 Hunter (A.) and Campbell, " The Placental Transmission of Creatinine and
Creatin," Jour, of Biol. Chem., vol. xxxiv., 1918.

FCETAL NUTRITION: THE PLACENTA 507

Ferments

Various enzymes have been investigated in the placenta. They
may be grouped according to the chemical nature of the actions
which they produce, as follows : (1) Hydrolytic reactions, (2) oxida-
tion reactions, (3) removal of amino groups from amino-acids, and
(4) decomposition of peroxides.

(1) A proteolytic enzyme was found by Ascoli,1 and subsequently
by Merletti,2 Bergell and Liepmann,3 Savare,4 and others. Bottazzi 5
states that placental tissue can transform glycogen into maltose, and
a similar action is strongly produced by glycerine extracts of the
maternal and fostal placenta of the rabbit (see p. 462).

Savare holds that the transformation of glycogen to sugar is due
to the blood ; but, the fact that extracts of the Ungulate placentae,
which also contain blood, do not possess the same power, forces us to
conclude that the enzyme activity in the rabbit and man depends on
the placental tissue. No lipolytic enzyme is present in the placenta
(Charrin and Goupil 6).

(2) The oxidation of aromatic aldehydes by the placenta has been
obtained by Hofbauer and by Ferroni,7 not by Savare or Charrin and
Goupil. V. Fiirth and Schneider 8 state that tyrosine is oxidised by
contact with the placenta, resulting in the production of a dark
pigment, and they have suggested that this reaction may be related
to the special pigmentation of pregnancy.

(3) Savare states that the placenta transforms the NH2 group of
amino-acids into ammonia by means of a special ferment, a desamidase.

(4) Decomposition of peroxides may be produced by enzymes, the
so-called indirect oxidas^, and is sometimes regarded as the means
by which oxidation changes are restricted to the appropriate parts of
the body, and secluded, for instance, from the blood (Leathes 9). The
guaiacol reaction, by which a colourless solution of guaiacol becomes
red, takes place, according to Charrin and Goupil, when hydrogen
peroxide is present ; in other words, placental tissue decomposes the
peroxide, and the nascent oxygen oxidises guaiacol. Hofbauer,

1 Ascoli, " Passiert Eiweiss die placentare Scheidewand ? " Zeitsch. f. phys.
Ckemie, vol. xxxvi., 1902.

2 Merletti, " Pacerche e studi intorno ai poteri selettivi del' epitelio dei villi
coriali," Ross. d'Ost. e. Cfinec., 1903.

3 Bergell and Liepmann, " Ueber die in der Placenta enthaltenen Fermente,"
Munch, med. Woch., 1905.

4 Savare, " Zur Kenntnis der Fermente der Placenta," Hofineister>s Beitrage,
vol. ix., 1907.

5 Bottazzi, " Placental Activity," Boll, della R. A c<:ad. med. Geneva, vol. xviii.
0 Charrin et Goupil, " Physiologic du Placenta," Compt. Rend, de UAcad. des

Sciences, vol. cxli., 1905 ; also vol. cxlii., 1906.

7 Ferroni, " L'eterolisi utero-placentare," Ann. di Ost. e Ginec., 1905.

8 V. Fiirth and Schneider, "Ueber tierische Tyrosinasen und ihre
Beziehungen zur Pigmentbildung," Hofmeister's Beitrage, vol. i.

9 Leathes, Problems in Animal Metabolism, London, 1907.

508 THE PHYSIOLOGY OF REPRODUCTION

however, says that the presence of hydrogen peroxide is not required,

i.i: that the placenta acts as a direct oxidase.

No glycolytic ferment is present in the placenta.1

A few ferment actions still remain — e.g. the removal of urea from

arginin, the decomposition of uric acid, and the oxidation of purine

bases — which have not yet teen investigated in the placenta.2

Y. GENERAL CONSIDERATIONS OF FCETAL NUTRITION AND
THE PLACENTA

A. The Plan of Placenta! Formation

The problems of foetal nutrition are not new problems. They
deal with the assimilation of organic and inorganic substances, and
their incorporation in the developing tissues. These phenomena are
made up of a series of chemical changes which must be studied
individually before we can hope to understand the final sum which
constitutes fwtal metabolism, or the disturbances which constitute
. foatal disease. Set in the path traversed by the materials on their
way to the new organism is the placenta, a complex organ composed
of specialised maternal elements and newly developed foetal elements.
Among the Monodelphia no uniform plan is observable in the
formation of the placenta, nor is it possible to trace each step in its
evolution. But Duval's conception of this temporary organ as a
maternal luuniorrhage surrounded by foetal elements, and Hubrecht's
discovery of such a type of placenta in a mammalian order wrhich is
among the most archaic, lead to a change in the ideas of placental
classification. We can no longer depend on the shape of the placenta
or the characteristics of the after-birth, for* an understanding of its
morphological or physiological features. Eather must we go back
to the phenomena to be observed in the uterine fixation of the
blastocyst, and even earlier in the preparation for that fixation. At
this stage we find two constant features, one maternal and the other
foetal. The maternal change consists of an epithelial, connective
tissue or endothelial proliferation, the trophospongia, which is
"specially intended for the fixation of the blastocyst." According'
to Hubrecht, it degenerates into a symplasma when the fixation is
accomplished and the foetal elements are in contact with circulating
maternal blood. But its degeneration is not completed at that stage.
Though individual cells may die, other cells are formed and take
their place, at least in man, throughout the greater part of pregnancy.
Moreover, the cells have other functions to perform. Whether or
not they act as a defence against the excessive penetration of the

1 It cannot yet be held as proved that glycolysis by ferment action occurs
at all in animals.

- For a further study of the ferment content of the placenta see above, p. 465.

FCETAL NUTRITION: THE PLACENTA 509

trophoblast, they continue in the rabbit to exercise the glycogenic
function for the developing organism till the hepatic cells have
attained the power, and there is reason to believe that they play a
part in the iron metabolism of the foetus.

The embryonic preparation is the proliferation of the whole or
part of the extra-embryonic ectoderm, the trophoblast, in the spaces
of which maternal blood circulates. The outer layer is plasmodial,
and thus resembles the maternal symplasma in histological appear-
ance, but differs from it in being a live tissue while the other is
dying or dead. The fusion of the trophoblast and trophospongia
constitutes the placenta, which is perfected by an increase in the
number and size of the trophoblastic lacuna?, and in the amount of
maternal blood in contact with it.

The above description does not, however, fit the placenta of
Ungulates, for in them the trophoblast is not permeated by maternal
blood. If the Insectivore placenta represents the primitive type, or
is nearer to it than any other at present existing, we must assume
that the Ungulate placenta, differing more widely from the original
type, has lost this characteristic. Further, the placenta of the pig
must have undergone a greater degree of modification than that of
the sheep. In other words, the old ideas of placental evolution,
based on the researches of Turner and others, must be literally
reversed. The Primates must stand with the Insectivores near the
primitive type, while the sheep and pig are near the opposite end,
where some of the Didelphia are placed. Such considerations as these
must inevitably come up for discussion in all future investigations.

B. The Nature of the Trophoblastic Activity

During the period of gestation, the mother organism is concerned
with the provision of material for the growth and development of the
fertilised ovum and the new-born young. Does the material
provided for the ovum, and secured for it by the trophoblast, come
from the maternal tissues or from the food supply ? There is no
doubt that in insufficient nutrition the fostus draws on the tissues of
the mother (Jagerroos 1), and a study of comparative placentation
goes far to prove that this is a normal process in some orders. It is
obvious that such occurs in the earliest stages. In all orders, before
fixation of the blastocyst to the uterine mucosa, the degenerating
ovarian cells which surround the -extruded ovum form a store of
nutriment. In some animals, however, such as the opossum, in
which no attachment of the blastocyst can be said to occur, and the
sheep, in which the attachment is long delayed, this nutriment is

1 Jagerroos, "Der Eiweiss-, Phosphor-, und Salzumsatz wahrend der
Graviditat," Arch. f. Gyniik., vol. Ixvii.

Sio THE PHYSIOLOGY OF REPRODUCTION

added to by the secretion of the uterine glands. In the so-called
Deciduate orders, fixation is effected by a phagocytic or chemical
action on the part of the trophoblast, and the destroyed maternal
tissue again seems to serve as food for the blastocyst.

After fixation, differences appear in the various orders. In
Ruminants a special nutritive secretion, the uterine milk, is
elaborated in the inter-cotyledonary areas. This secretion contains
cellular elements of maternal tissue, particularly leucocytes and
glandular epithelium, which are ingested and dissolved by tin;
trophoblast during the whole period of gestation. In addition,
extravasations of maternal blood or individual corpuscles occur in all,
and the erythrocytes are also taken up and dissolved. In such orders
maternal tissue elements are normally used for the fcetus throughout
pregnancy.

Among the Deciduata, however, with the exception of the mole,
in which the glandular secretion is maintained, the maternal blood
may be considered to be the only source of foetal nutriment when
the allantoic or chorionic placenta is developed.1 In them the
trophoblast resembles a sponge saturated with slowly circulating
blood, and its large superficies is admirably adapted for the
acquisition of the various materials required for the foetus. In what
form do these materials exist in the blood ? Are they simply the
substances absorbed from the food by way of the intestine (see also
Chapter XI., p. 521), or are they more highly elaborated ? In other
words, in the formation of the new organism are the syntheses
. carried out by the fertilised ovum itself, and it must be remembered
that this includes the trophoblast, or are the new tissue-elements
transferred ready-made from the mother ? The limitations of
biological chemistry force us to approach this problem indirectly.
Differential analyses of special constituents of the blood, as the pro-
teins, in the non-pregnant and pregnant animal are not yet possible.

In the first place, a brief consideration of the development of the
chick embryo is sufficient to prove the high degree of activity vested
in the ovum of birds. The special proteins and other tissue-elements
are not pre-formed, but are elaborated by a series of katabolic and
anabolic processes which are carried out by the ovum itself. There
is no reason to believe that the mammalian ovum, after acquiring the
property of intra-uterine development, has lost its metabolic activity.2

1 The Carnivora, in which the trophoblast is not in contact with circulating
maternal blood, occupy a special position among the Deciduata, and are not
considered above.

2 If Hubrecht's view is correct, that the mammalian ovum is older than
the ovum of birds (see "Early Ontogenetic Phenomena in Mammals," Quar.
Jour, fificr. Science, 1908), the sentence ought to read : "There is no reason to
believe that the fertilised ovum of birds acquired its metabolic activities only
after the loss of viviparity."

FCETAL NUTRITION: THE PLACENTA 511

In addition, we possess positive evidence of metabolic activity in
the mammalian ovum. The results of Bohr's investigations on the
respiratory exchange of the foetus (see p. 464) mean nothing if they
do not afford proof of this. As a large amount of energy is generated,
while, at the same time, practically none is dissipated as heat
evaporated or radiated from the surface or lungs, the unavoidable
conclusion is that the foetus itself carries out the work of organisa-
tion, and utilises the energy for its fulfilment.

When we come to consider individual substances, we obtain
further evidence of activity, at least in the extra-embryonic ectoderm
or trophoblast. In no order of Mammals has the transmission of
haemoglobin as such from mother to foetus been demonstrated. Even
if it is absorbed as such by the trophoblast, it undergoes changes of
such a nature that the iron-containing part of the molecule is less
firmly bound. In all animals in which special investigations have
been made, such loose organic compounds of iron have been observed.
In this connection, reference may once more be made to Hofbauer's
statement that the histological appearances argue not only for a
decomposition of maternal haemoglobin in the syncytium, but also for
a synthesis of its derivatives into organic compounds in which the iron
is more firmly bound (see p. 505).

The trophoblast probably acts also on simpler proteins. If ox-
serum is injected into a pregnant rabbit, its proteins cannot be
detected by the biological reaction in the semm of the foetus. It
may be that the trophoblast rejects them altogether, but this is
unlikely, since molecules of egg-albumen are absorbed and transferred
to the foetus (see p. 464). In all probability the proteins of ox-serum
are katabolised in the villi, and, as a result, the constitution of the
precipitable substance is interfered with, and the precipitin reaction
is negative. The existence of an intra-cellular proteolytic enzyme l
and decomposition products of the proteins in the placenta also point
to the occurrence of a trophoblastic metabolism of proteins.

The carbohydrates undergo changes which appear to be the result
of 'trophoblastic activity. In the rabbit, the glycogen which is
"swallowed" along with the decidual cells by the plasmodium
(Chipman) is not found as glycogen. A hydrolytic transformation
to sugar probably takes place (see p. 462). In addition the foetal
serum contains Irevulose, which must be formed in some part of the
fertilised ovum, since it is absent in the mother. Fats may also be
transformed by the trophoblast (see Chapter XI., p. 542).

1 It is desirable that the presence of the enzyme in the trophoblast should
be established, and this can only be done in such animals as the sheep and
rabbit, in which the foetal placenta can be detached from the maternal, and
investigated separately. As was previously mentioned, the placenta contains
uo extra-cellular proteolytic enzyme.

512 THE PHYSIOLOGY OF REPRODUCTION

It is generally supposed that many syntheses occur in the
fertilised ovum, though direct evidence is difficult to obtain in
Mammals. In the chick haemoglobin is synthesised, and the same
almost certainly occurs in man and other animals, part of the
synthesis being effected by the trophoblast (see p. 505). The
nucleoproteins of the foetal cotyledons in the sheep appear to be
formed there, since they differ in composition from the nucleoproteins
of the cotyledonary burrs. The glycoprotein mucin is a characteristic
constituent of the intercellular ground-substance of the whole foetal
organism, and is apparently built up by the ovum.1 The chondro-
proteins, a special group of glycoproteins, which yield on hydrolysis
proteins and the carbohydrate-containing chondroitin-sulphuric acid,
are also found chiefly in the frjetus as constituents of the cartilage
and tendons.

A consideration of these and similar facts leads us to believe that
the new organism owes its development in large part to the energy
generated in it and by it from the combustion of substances supplied
by the mother, and to a series of active metabolic changes by means
of which these substances are transformed into living protoplasm.
Whether the nutritive materials are derived from the food or tissues
of the mother is of secondary importance. What is essential is that
the fertilised ovum obtains certain organic and inorganic compounds
and a supply of oxygen to carry out its work of organisation, just as
in the first period of extra-uterine life the growth and development
of the new being progress by its own activities, so long as it is
furnished with the proper materials.

The special organ of embryonic nutrition is the trophoblast, and
evidences of its katabolic activities have been described in various
orders of Mammals. But in addition to procuring fixation of the
blastocyst to the uterine mucosa, and absorbing and katabolising
the food for itself and the embryonic portion of the ovum, it seems
also to possess anabolic fimctions, at least in the earlier periods of
pregnancy. Already developed in the blastocyst stage, it is active
.and functional for a considerable time. But in the later stages
it exhibits in all orders of Mammals a degree of morphological
degeneration which is incompatible with the maintenance of its
early physiological activity. It is further to be noted that its
condition varies inversely with the food requirements of the embryo.
When the daily requirements for the new organism are almost
infinitesimal, the trophoblast is well developed. But as the daily

1 In the placenta of the cow, Jenkinson has described cells resembling
goblet-cells in the lining of the cotyledonary crypts, and ascribes to them a
maternal origin (Proc. Zool. *SW., London, vol. i., 1906). They may supply
mucin to the uterine milk, and so to the trophoblast. According to Assheton,
these lining cells are trophoblastic in the sheep.

FCETAL NUTRITION: THE PLACENTA 513

transmission of nutriment increases, the .trophoblast, which is now
represented by the ectodermal covering of the villi, gradually and
progressively degenerates. At the end of pregnancy the cytoblast,
the mother zone of the plasinodiblast, is reduced to a few scattered
groups of cells, while the plasmodial layer itself is no thicker than
an endothelium, and may be altogether absent over long stretches
of the villi. At this stage it is impossible to believe that the
syncytium has. any vital functions to perform. Indeed, we know
that it has none, because the foetus, if prematurely born, is able to
maintain life without its aid. Hence it seems likely that in the
later stages the extra-embryonic ectoderm, though allowing a greater
amount of material to pass to the foatus each day, acts merely as a
semi -permeable membrane, and has lost all, or nearly all, its
physiological activity.1

What is the difference in the early stages of pregnancy, when
the trophoblast is morphologically well-developed < We believe that
at that time the extra-embryonic ectoderm has less to do with the
quantity, and more with the quality, of the material transferred to
the new organism. It does not act merely by the physical laws of
diffusion and osmosis. At this stage the cells of the ovum have not
yet departed widely from a general type, and the active trophoblast
would seem to spare the embryonic cells much of the work of the
elaboration of the food materials, and thus conserve their energies
for their own multiplication and differentiation. As the cells
gradually depart further and in different directions from the original
type, each cell requires to expend less energy on its own specialisa-
tion ; at the same time, the nutritive wants become more varied, and
each cell requires to expend more energy on the synthesis of its
individual protoplasm. As the duties of selection and anabolism are
more and more taken up by the cells themselves, the trophoblast has
a less important part to play, and it undergoes a gradual process of
degeneration.'2

1 Hofbauers observations on the haemoglobin metabolism, already quoted
(see p. 505), furnish concrete evidence of such a change in the trophoblast.
In the first half of pregnancy the syncytium breaks down the maternal haemo-
globin, and subsequently builds it up in part for the foetus. But in the second
half, though a greater daily supply of organic iron is required for the formation
of haemoglobin and other purposes (see p. 547), the amount of loosely bound
iron-compounds in the villi is "extraordinarily small." The only explanation
is that the larger molecules of the more firmly combined iron-compounds are
not attacked and broken down so strongly by the syncytium, but are passed
on to the foetal circulation.

2 A similar change occurs in the decidual cells of the rabbit. In the first
periods of their existence, they synthesise and store a large quantity of glycogen.
In the last week, the cells of the foatal liver assume their glycogenic function,
apparently absorbing the carbohydrate from the fittal blood as it returns from
the placenta, and the decidual cells degenerate with the loss of their function.

CHAPTER XI

THE CHANGES IN THE MATERNAL ORGANISM
DURING PREGNANCY1

:

" We cannot reason with our cells, for they know so much more than we
do that they cannot understand us ; but though we cannot reason with them,
we can find out what they have been most accustomed to, and what therefore
they are most likely to expect ; we can see that they get this, as far as it is in
our power to give it them, and may then generally leave the rest to them.''-
SAMUEL BUTLER.

I. THE STIMULUS FOR THE' MATERNAL CHANGES

THE anatomical and physiological changes which occur in the
maternal organism during pregnancy are manifold. They affect not
only the generative system, but the body in general. They are
associated with the supply of nutriment and energy for the formation
of a new organism in the uterus, and the preparation for its mainten-
ance in the succeeding period.

What constitutes the original stimulus for the changes that occur
in pregnancy remains still outside our ken. At least the influence of
the cerebrum is not all-important, as is shown by the occurrence
of normal pregnancy and lactation in women suffering from paraplegia
(Brachet,2 Kruieger and Offergeld3). Similarly, transection of the
spinal cord in the lumbar region has no effect on pregnancy in the
dog (Goltz 4). Further, Goltz and Ewald 5 have proved the absence
of any spinal reflex influence in the dog by removing the entire
lumbar cord without disturbing the onset and progress of pregnancy.
Kruieger and Offergeld state, as the result of numerous experiments,
that the central nervous system lias no influence, and the sympathetic
system has an effect only in so far as it modifies the circulatory
conditions. The only change observed, after destruction of the
lumbar cord, was a prolongation of the act of parturition, due to an

1 By James Lochhead and \V. Cramer.

- Brachet, Rechwhes, 2nd Edition, Paris, 1837.

3 Kruieger and Qffergeld, '' Der Vorgang von Zeugung, Schwaugerschaft,
etc.," Arch.f. Gyitcik., vol. Ixxxiii., 1908.

4 Goltz, " Ueber den Einfluss des Nervensystems auf die Vorgauge wahrend
der Schwangerschaft, etc.." Pftiiger's Arch., vol. ix., 1874.

5 Goltz and Ewald, " Der Hund mit verkiirztem Ruckenmark," /'//»//''/.<
Arc/i., vol. Ixiii.. 18<>fi.

514

CHANGES DURING PREGNANCY 515

absence of pain and the consequent loss of the reflex contractions of
the abdominal muscles. The most important nervous elements for
the uterus are contained in the uterine, paracervical, and paravaginal
ganglia, but their excitability to external stimuli gradually decreases
during pregnancy and is lost at the end.

We are thus forced to conclude that the phenomena of pregnancy
and parturition are brought about by chemical stimuli acting through
the blood-stream. The hormone or hormones may arise in the corpus
luteum, which is essential for the progress of pregnancy, at least in
the early stages (Marshall and Jolly 1). Evidence is also forthcoming
that the mammary secretion is due to an ovarian influence in certain
cases. For instance, secretion may occur in virgin women who are
the subjects of ovarian tumours, and in virgin bitches. Cramer 2 has
recorded a case in which the transplantation of ovaries into a woman,
whose genital organs were much atrophied, led to a secretion of
colostrum.3 On the other hand, removal of the ovaries at the middle
of pregnancy does not interfere with the second half of the period of
gestation, or with labour and lactation.

The presence of the placenta may modify the normal metabolism
in various ways. It is set in the path traversed by the formative
material on its way to the embryo, and by the waste products excreted
by the embryo. The form in which the materials required by the
product of conception reach the placenta is still obscure. The protein
may be merely the " circulating protein " found in the non-pregnant
condition, or more highly elaborated. The diffusion of the blood-sugar
to the foetus is disputable,4 and the form of the fats is unknown. Of
the waste products carbonic acid, which, according to Bohr,5 results
entirely from the combustion of carbohydrates in the mammalian
foetus, is excreted into the maternal circulation through the placenta.
With regard to a wastage in the protein metabolism, a certain loss
is bound to occur in the transformation of "circulating" or "fixed"
maternal proteins into foetal tissue proteins ; and in addition, incom-
pletely oxidised substances may possibly be transmitted to the
placenta and oxidised there or in the mother (Bohr6). The question
of urea formation by the fretal liver or the trophoblast still awaits
investigation. The only observation bearing on this point is that

1 Marshall and Jolly, " The Ovary as an Organ of Internal Secretion," Phil.
Trans. Roy. Soc., London, B., vol. cxcviii., 1905.

2 Cramer (H.), "Transplantation menschlicher Ovarien," Munch, med.
Woch., 1906.

3 With regard to the existence of an ovarian stimulus, see also Hildebrandt
(ffofmeisterfg Beitrdge, vol. v., 1904). s

'4 See Chapter X., p. 462.

'"' Bohr, " Dei1 respiratorische Stoffwechsel des Saugetierembryo," Skand.
Arc/i. d. F/ii/g., vol. x., 1900 ; also vol. xv., 1904.

6 Bohr, see Nagel's HatncRntck der Physiologw, " Respiration," vol. L, H. i.

516 THE PHYSIOLOGY OF REPRODUCTION

of Hammett,1 who found that the human placenta contains urea, and
that the urea content is greatly increased in this organ in toxsemic
pregnancies. He also found that urea is formed when the placenta is
allowed to undergo autolysis. No proof exists of the excretion of urea
otherwise than into the liquor anmii. Nor does its presence in the
amniotic fluid necessitate an oxidation of protein ; it may be split off,
as in the adult, by a simple hydrolytic cleavage. At present we must
be content with assuming the possibility of modifications in the
maternal blood from the presence of foetal nutritive and waste
materials. Hitherto the investigations have been largely confined to
human pregnancies, in which individual differences are at a maximum,
and the application of the experimental method is restricted. Hence
our knowledge of the chemical changes in the blood is very limited.
Its composition may, in addition, be modified by the activities of the
placenta itself. Several theories have been put forward in support
of the view that this organ acts as an internally secreting gland.
Nattan-Larrier 2 goes so far as to state that the secretion can be
demonstrated in the form of globules lying on the surface of the villi,
but these arise in the post-mortem degeneration of the tissue. Of the
same nature are the products of the placenta which have a blood-
pressure raising action. Extracts of the fresh organ have no pressor
effects, nor do they increase uterine contractions.3 Halban 4 considers
that the placenta secretes a hormone which stimulates the growth of
the mammary gland and the secretion of milk.5 Starling 6 suggested,
on the other hand, that the hormone was contained in the tissues of
the foetus, that by its activity during pregnancy it led to a prolifera-
tion of the mammary tissue, and that the cessation of the stimulus
after parturition brought on the secretion of milk.

According to Liepmann,7 the maternal blood contains a special
protein, elaborated by the placenta, which may be recognised by the

1 Hammett, "The Urea Content of Placentas from Normal and Toxsemic
Pregnancies," Jour. Biol. Chem., vol. xxxiv., 1918 ; " Urea Formation by the
Placenta," ibid., vol. iii., 1919.

2 Nattan-Larrier, "Fonction Secretoire du Placenta,," Compt. Rend. Soc.
Biol., vol. Hi., 1900.

3 See footnote 6, p. 557.

4 Halban, " Die innere Secretion von Ovarium und Placenta, und ihre
Bedeutung fur die Function der Milchdriise," Arch. f. Gyndk., vol. Ixxv., 1905.

5 In future investigations, the better recognition of the composite structure
of the placenta is desirable. In many animals it is possible to separate the
maternal and foetal tissues with considerable accuracy, and any effect obtained
from one or other part can be definitely ascribed to the modified uterine
mucous membrane, or to the extra-embryonic part of the ovum.

6 Starling, " Chemical Correlations of the Functions of the Body," Croonian
Lesjures, Lancet, 1905. Starling appears, however, to have abandoned this
theory in view of the more recent work on the functions of the corpus luteum
(see p. 616). '

7 Liepmann, " Ueber ein fiir menschliche Plazenta spezifisches Serum,"
Deut. med. Woch., 1902, 1903.

CHANGES DURING PREGNANCY 517

biological reaction, and Freund l states that a precipitable substance
is present in the urine of pregnant women. Others have been unable
to find such a substance either in the blood or urine (see Weichardt
and Opitz 2).

Veit's 3 theory is also sub judice. Taking up Schmoii's 4 discovery
that eraboli of placental cells may be found in organs of the mother
in eclampsia, he extends it to normal pregnancy, and postulates that
syncytial fragments and even whole villi pass regularly into the
maternal circulation. There they give rise to an anti-body, a
syncytiolysin, which itself dissolves the circulating syncytium. He
also seeks to explain, by the activity of the lysin, the absorption
of haemoglobin and other proteins from the intervillous space by the
villi, the pigmentation of the skin and vaginal mucous membrane
from superficial emboli, and the phenomena of telegony from the
circulation of elements derived in part from the paternal side.5

At present it is only a speculation, as Veit himself is careful to
explain, but its far-reaching possibilities have already given rise to
many investigations.0 It must be clearly understood, however, that
biologists have at present no convincing proof of the formation of
an anti-body consequent on the introduction of any protein of the
same individual, or one of the same species.

Abderhalden 7 claimed to have obtained evidence of the formation
of specific ferments arising in the maternal organism as the result
of the formation of the placenta. These ferments, which he calls
" defensive ferments," were stated by him to have a specific action
on the proteins of the placenta, and their formation was regarded by
him to be the result of the reaction of the body against the presence
of substances foreign to the blood. He elaborated a technique
which renders it possible to recognise the presence of a placenta
by the presence of these ferments ; the so-called " Abderhalden

1 Freund, " Beitrage zur Biologic der Schwangerschaft," Vortr. auf d.
76 Naturf. zu Breslav, 1904.

2 Weichardt u. Opitz, u Zur Bioehemie der Schwangerschaft," Deut. med.
Woch., 1903.

3 Veit, " Ueber Deportation von Chorionzotten," Zeitsck. f. Geb. u. Gyntik.,
vol/ xliv. Also Veit u. Scholten, " Synzytiolyse und Hamolyse," Zeitscli. f. Geb.
u. Gyndk., vol. xlix., 1903.

4 Schmorl, Path.-Anat. Untersuclmngen iiber die Puerperalekla/mpsia, Leipzig,
1893.

5 The discussion of the relationship between the deportation of chorioniu
villi and the pathology of eclampsia, pregnancy kidney, placental polypi,
hyperemesis, etc., falls outside the scope of this work. A critical summary
of recent work on this subject is given in Medical Science, vol. v., 1921, p. 537,
in a review entitled " The Biochemistry of Eclampsia."

6 See Kollmann, "Kreislauf der Plazenta, Chorionzotten und Telegonie,"
Zeitsch. f. Biol., vol. xlii., 1901. Hinselmann, Die angebliche physiologische
Schwangerschaftsthrombose von Gefdssen der uterinen Plazentarstelle, Stuttgart
(F. Euke), 1913.

7 Abderhalden, Abwehrfermente, Berlin, J. Springer, 1914, 4th Edition.

5i8 THE PHYSIOLOGY OF REPRODUCTION

reaction for the diagnosis of pregnancy." His claims, which he
extended to various pathological conditions of other organs, were
at first widely and somewhat uncritically accepted and gave rise to
an extensive literature. They have, however, not stood the test of
experimental criticism l and his views are no longer accepted.

From time to time evidence of haemopoiesis in the placenta has
been brought forward. Mention of it was first made by Masquelin
and Swaen 2 in the rabbit, and later by Frommel 3 in the mouse and
bat. Hubrecht4 strongly upholds the occurrence of blood formation
in the placenta1 of Tarsius and Tupaia. The new erythrocytes arise
as products of the fragmentation of nuclei of the trophoblast in
Tarsius (see p. 440), and of the trophoblast, and probably also
trophospongia, in Tupaia (see p. 485). They are later set free by
solution of the surrounding protoplasm. Such a process is beneficial
both to mother and embryo. The erythrocytes are increased at the
expense of the ovum, and they in turn increase the supply of oxygen
to the fetus.

II. CHANGES IN THE METABOLISM OF THE MOTHER
DURING PREGNANCY

General Considerations

How does the maternal organism react to the presence of a
rapidly growing mass of tissue, namely the fostus and adriexa ?
An idea of the food and energy requirements which the presence
of the fetus imposes upon the maternal organism can be formed
from the following data. The table is a very condensed summary
of the figures calculated or obtained by Hoffstrom 5 in his investi-
gation on the human subject, a primigravida living on an unrestricted
diet. The figures give the total amounts in grammes of nitrogen,

1 Bullock, "A Critical Study of the Basis of Abderhalden's Serum Reaction,"
The Lancet, i., p. 223, 1915. Van Slyke and others, "The Abderhalden
Reaction," Jour. Biol. Ckem., vol. xxiii., 1915. Falls and Walker, "The
Influence of Pregnancy on the Proteolytic Activity of Blood-Serum," ibid.,
vol. xxxii., 1917. Hulton, "The Formation of Specific Proteoelastic Enzymes
in Response to Introduction of Placenta," ibid., vol. xxv., 1916. Jobling,
Eggstein, and Petersen, " Serum Proteases and the Mechanism of the Abder-
halden Reaction," Jour. Exp. Med., vol. xxi., 1915.

2 Masquelin and Swaen, " Developpement du placenta maternel chez le
lapin," BiM. de PA cad. Roy. de Belgique, 1879.

3 Frommel, Ueber die Entiowklung der Placenta ron Mijottts murinus,
Wiesbaden, 1888.

4 Placental haemopoiesis is denied by many authorities, including Duval,
Maximow, Nasius, and Nolf. For a complete review of the subject, see
Hubrecht, " Ueber die Entwicklung der Placenta von Tarsiius und Tupaja,
nebst Bemerkungen iiber deren Bedeutung als haematopoietische Organe,"
Internal. Congr. of ZooL, Cambridge, 1898.

6 Hoffstrom, "Ein Stoffwechseluntersuchung wahrend der Schwangerschaft,"
Skandin. Arch. f. Physiol., vol. xxiii., 1910.

CHANGES DURING PREGNANCY

519

phosphorus, calcium and magnesium actually present at given times
in the fertilised ovum, i.e. the fetus with adnexa, and also the
amounts which have been retained per week by the fertilised ovum.

N.

P. Ca.

Mg.

of
Preg-
nancy.

Content
of
Ovum.

Weekly
Require-
ments of
Ovum.

Content ; Weekly
of Require-
Ovum. imenteof
i • Ovum.

Content
of
Ovum.

Weekly
Require-
ments of
Ovum.

Content
of
Ovum.

Weekly
Require-
ments of
Ovum.

16

4-28

1-13

0-67 0-20

0-38

0-02

0-026

0-0016

20

8-81

1-82

1-47 0-25 2-03

0-43

0-095

0-0173

24

16-07

1-80

2-48 0-27 3-74

0'41

0-164

0-0175

28

23-28

6-87

3-58 1-28 5-39

2-09

0-234

0-0642

40

105-76

6-87

18-93 1-28 30-51

2-09

1-004

0-0642

Bar1 has calculated the following figures for the human fetus
without adnexa.

Period.

Till 4 months -
During 4th month -

„ 5th „ -

„ 6th „

„ 7th „

8th and 9th months

Daily N
Requirement.

0-0013 gm.

0-042

0-155

0-166

0-198

0-945

The additional energy requirements have been determined by
Murlin2 for the pregnant dog and by Carpenter and Murlin3 for
the human subject. In a bitch weighing about 14 kg. during sexual
rest the following figures were obtained during two different preg-
nancies three days before birth.

Condition.

Total Energy in Total Weight of
Calories. Puppies in Grammes.

Sexual rest after lactation

505-3

1st pregnancy, one puppy born

551-3

280

2nd pregnancy, live puppies born

763-8

1,560

1 Paul Bar, J^econs de L'atholofjie obstetrical'', vol. ii., Paris, 1907 (Asselin et
Houzeau, editeurs).

. - Murlin, ''Energy Metabolism of the Pregnant Dog," Amer. Jour, of
I'/itfsioL, vol. xxvi., 1910.

3 Carpenter and Murlin, " Energy Metabolism of Mother and Child just
before and just after Birth," Archives of Int. Medicine, vol. vii., 1911.

520 THE PHYSIOLOGY OF REPRODUCTION

The extra energy production at the end of pregnancy is therefore
proportional to the weight of the offspring to be delivered. The
increase over the metabolism of the mother during sexual rest
amounted to about ten per cent, in the first pregnancy and to as
much as fifty per cent, in the second pregnancy with five puppies.

In the human subject, where the weight of the fcetus in proportion
to that of the mother is much smaller, the energy metabolism
expressed per kilogramme and hour is in the last month of pregnancy
only four per cent, larger than for a woman in complete sexual rest :
0*99 Cal. per kg. and hour in the latter condition, 1*03 Cal. per kg.
and hour in the pregnant woman. This quantitative difference must
be borne in mind in comparing observations on pregnant dogs with
those on human subjects. Whatever changes occur are likely to.be
more pronounced and acute in the dog.

Directly or indirectly the mother must provide the additional
energy and food materials necessary for building up and maintaining
the developing embryo. Does this entail a sacrifice on the part of
the mother ? At first sight one would conclude a priori that this
must necessarily be the case. This idea gradually developed into
the conception that pregnancy involved a pathological condition of
the maternal organism, and a good deal of experimental evidence
was adduced in support of the view that in pregnancy the oxidative
processes in the organism are essentially different from the normal.
This view found its extreme expression in the dictum of Massen l
that " a pregnant woman is by the diminished oxidation brought
into a condition of auto-intoxication very similar to that produced
in an animal with an Eck's fistula," where the blood flows from the
portal vein directly into the vena cava, without passing through
the liver. Similarly, Ewing z speaks of a " liver of pregnancy " and
holds that normal pregnancy produces changes, especially in the
liver, " difficult to separate from the pathological."

But more recent observations, especially the magnificent work of
Bar3 and his collaborators, which has been confirmed in its main
results and extended by the careful investigations of Hoffstrom 4 and
Murlin,5 have shown that in " a normal pregnancy the maternal
organism is very far from being in a pathological condition, and that

1 Masseu, Proc. Soc. for Obstetrics and Gyncecology of St. Petersburg, Feb.
1899 ; Zeitsch. f. Geburtshi'dfc, vol. x. ; quoted from Bar, see below.

2 Ewing, "The Pathogenesis of the Toxaemia of Pregnancy," A me): Jour,
of Medical Sciences, vol. cxxxix., 1910.

3 Paul Bar, loc. cit.

4 Hoffstrom, loc. cit.

5 Murlin, "The Metabolism of Development," I., II., and III., Amer. .lour,
of PhysioL, vol. xxvi., 1910 ; vol. xxvii., 1910 ; vol. xxviii., 1911. A summary
of these papers is given in the paper by Murlin, "The Nutrition of the
Embryo," Trans, \btlt luternat. Coiiyregs of Hygiene, September 1912.

CHANGES DURING PREGNANCY 521

both the experimental data which formed the basis of the pathological
conception of pregnancy and the arguments on which it was built up
were open to criticism.

In a normal mother carrying a healthy foetus and living on an
adequate diet, pregnancy does not entail a sacrifice on the part of the
mother. In the words of Bar : " L' etude de la balance azotee n'autorise
pas a dire qu'en principe le gestation constitue mie periode de
sacrifice ; elle montre au contraire qu'elle pent etre et qu'elle est
souvent une periode de profit. La gestation apparait done coinme un
exemple de symbiose harmonique homogene."

The various aspects of the metabolism of pregnancy will now be
discussed in greater detail.

A. The Source of the Materials transferred to the New Organism,

The question is discussed in another chapter (see p. 509) whether
the materials that go to the formation of the new organism are
elaborated entirely in the new ovum itself, or are wholly prepared by
the mother. As stated there, the histological and biological evidence
leads us to believe that the materials, whatever their source and
constitution, are in the early stages broken down and partly re-
synthesised by the trophoblast, while later in pregnancy they are
metabolised by the total cells themselves. Granting this, we must
further suppose that the maternal duties do not extend to the formation
of total tissue-components, but are limited to the provision of food
and oxygen for the fertilised ovum, the removal of its waste products
and the preparation of an organ of nutrition for the new-born young.
Each of these duties leads to changes in metabolism, which may, in
addition, be excited by special stimuli produced din-ing pregnancy
(see p. 515).

In the provision of nutriment for the embryo, does the mother
deplete her own tissues, or is she content to transfer the unorganised
substances which are absorbed from the food and not yet fixed as
vital constituents of the protoplasm ? Probably both. In insufficient
nutrition the mother certainly gives up organised tissue-products,
and even with a plentiful diet a period has been observed in the dog
in the earlier stages of pregnancy (see p. 527) during which the
maternal organism loses nitrogen and therefore draws on its own
tissues. On the other hand, in the later stages of pregnancy when
the requirements of the foetus are greatest there is on an adequate
diet a considerable retention of nitrogen. This is brought about, as
will be seen, by a more perfect assimilation of the absorbed food. At
this stage, therefore, the unorganised substances of the absorbed food
are apparently being utilised directly by the trophoblast. This
17 A

522 THE PHYSIOLOGY OF REPRODUCTION

conclusion finds confirmation in the observation that variations in
diet are apparently capable of producing chauges in the ftetus.1 It
was noted by Lochhead and Cramer2 that abortion occurred in
three out of six pregnant rabbits fed on a diet rich in carbohydrates
during the whole period of gestation. A similar observation is
recorded 1 »y Cramer and Marshall.2 Wallace 3 states that cows fed
on molasses prove to be uncertain breeders, and Heape 4 that Lincoln
sheep fed solely on turnips are specially liable to abortion.

According to Noel Paton,5 the size of the offspring of the guinea-
pig depends very directly upon the diet and nutrition of the mother
during pregnancy. " To the physiologist it demonstrates the limita-
tions in the extent to which the tissues of the mother can be utilised
for the construction of the embryo. The nourishment of the maternal
tissues seems to take precedence over the nutrition of the foatus.
The mother appears to pass on the surplus nourishment to the foetus.
The bettei the nourishment of the maternal tissues, the greater the
growth of the foetus." This generalisation is too sweeping. Observa-
tions on rats G have shown that the weight of the offspring remained
the same on different diets, although on one diet the mother increased
in weight during pregnancy while on the other it lost in weight.
Further, it has been proved in the pregnant rabbit that, when the
glycogen of the body is reduced to traces by repeated injections
of phloridzin, the placenta and foetus still retain considerable amounts.7
In this instance the needs of the foetus have taken precedence over
the storage of a carbohydrate reserve for the mother. Like Paton,
Prochownick 8 states that the size of the ^offspring may be markedly
diminished by restricting the diet of the mother (human female) ; but
many exceptions to this rule are found, which in fact comes into
operation only when the restriction of food has been severe enough
to jeopardise the health of the mother.

This opens up another question : Does the expenditure for the
embryo entail loss to the mother ? " If the mother must transfer
a part of her own bodily substance to the germ, the loss is of little

1 Thiemich was, however, unable 'to discover any difference in the constitu-
tion of the foetal fat, after feeding the mother on widely different fats
(see p. 543).

2 See Cramer and Marshall, " A Note on Abortion as a result of a Diet rich
in Carbohydrates," Jour, of ECOH. Biol., vol. iii., 1908.

3 Wallace, Farm Live Stock; 1907.

4 Heape ascribes the frequency of abortion to the fouling of the turnip-roots
by mud and excrement, a condition of things which results from overcrowding.
See Jour. Roy. Agric. Soc., 1899.

5 Noel Paton, " The Influence of Diet in Pregnancy op the Weight of the
Offspring," Lancet, 1903.

6 Cramer (W.), Unpublished observations.

7 Lochhead and Cramer, " The Glycogenic Changes in the Placenta and the
Fostus of the Pregnant Babbit," Proc. Rot/. .S'or. London, B., vol. Ixxx., 1908.

8 Prochownick, T/ierap. Momit*lieft<>, 1901, quoted by Paton (foe. fit.).

CHANGES DURING PREGNANCY 523

importance if she can cover this loss from her food. The setting of
the question runs thus: Is the maternal body deprived of protein,
fat, and other substances during and in consequence of the formation
of a new being, and is its store of these materials, after the resulting
birth, or at the close of the puerperium, less than before the advent
of pregnancy, or is this not the case ? An unprejudiced clinical proof
from human subjects points to the possible occurrence of both
conditions. Man}' mothers during pregnancy increase so slightly in
weight that their own tissues must have suffered loss during this
time, others become heavier to the extent of ten kilograms or more.
The investigation has not to determine whether the maternal organism
suffers loss or experiences gain, but to demonstrate under which
conditions of nourishment the one or the other appears. It has to
investigate whether and in what amount the needs of the mother are
increased, if her original condition is to remain unaltered while new
tissues are being formed " (Magnus-Levy 1).

B. The Body-weight during Pregnancy

Systematic determinations of the body-weight give some idea
of the effect of pregnancy on the. maternal organism as a whole.
Gassner2 observed a progressive increase in weight, greater than
the increase in the weight of the foetus (about 1 kilo per month)
and the generative organs (about 01 25 kilo per month) together.
This is due to the increase in the other parts of the maternal
organism as a " result of the inactivity and good dietetic conditions
during pregnancy, and the frequency with which the tissue fluids, e.g.
in the lower extremities, are increased." Baumm 3 confirmed these
results. A diet necessary to maintain the body-weight in a woman of
the same size gave an increase in weight of a pregnant woman amount-
ing to an average of 1'777 kilo in the last month, of which 0'650
kilo represented increase outside the foetus and generative organs.

Zacharjewsky 4 observed an increase in weight running parallel
to the increased weight of the foetus and uterus. Some days before
birth he found a decrease in primiparse and a balance in multipart,
which he referred to Ahlfeld's observations that the foetus increases
only up to the thirty-ninth week, and in the last week decreases.

There are, however, limitations to the estimation of the total

1 See v. Noorden, Metabolism and Practical Medicine, vol. i., section on
" Metabolism of Pregnancy."

2 Gassner, " Ueber die Veranderung des Kb'rpergewichtes bei Schwangeren,
etc.," Monatsschr. f. (jfeburtsk. u. Frauenkrankh., vol. xix., 1862.

3 Baumtu, " Gewichtsveranderungen der Schwangeren, etc.," I iiaug.- Dissert.,
[iinchen, 1887.

4 Zacharjewsky, " Ueber den Stickstoffwechsel wahrend der letzten Tage
ler Schwangerschaft, etc.," Zeitsch. f. Biol.t vol. xxx., 1894.

524 THE PHYSIOLOGY OF REPRODUCTION

metabolism by the alteration in weight. Thus Bar and Daunay1
discovered no increase of weight in a pregnant dog, though it had
retained 5'24 gm. nitrogen, equal to 170 gm. flesh. Similarly,
Hoffstrom, in a primigravida, found a total retention of 209 gm.
nitrogen during pregnancy which could not be accounted for by the
slight increase in weight. Such a discrepancy may perhaps be
explained, partly at any rate, by a loss of water. In Man the
physiological variation in the water-content is as much as 2 kilos.
And in Hoffstrom's case the slight increase in weight was accom-
panied by a loss of fat. In any case this unusual discrepancy
between weight and nitrogen retention, which requires further
explanation, indicates a remarkable alteration in the metabolism of
the maternal organism. Hence it is necessary to obtain a more
accurate measure, and for this purpose to investigate separately the
metabolism of various substances : proteins, carbohydrates, fats,
minerals, salts, and oxygen.

C. The Protein Metabolism in Pregnuncy

(a.) The Absorption of Proteins by the Mother.— According to
Kehrer,2 the gastric functions are slightly below normal in the
human female during pregnancy. Free hydrochloric acid and pepsin
are each decreased by a third. At the same time the intestinal
functions appear to be sufficiently active for the satisfactory absorp-
tion of nutriment.

The absorption of flesh does not show any characteristic change
in the dog during pregnancy. If decreased, it is due to pathological
conditions, and diarrhoea and vomiting are present (Bar and Daunay).
Ver Eeke3 states that the absorption of nitrogen decreases in the
sscond half of pregnancy in the rabbit, but he ascribes the change
to mechanical conditions. Maurel4 is of opinion that a gradual
decrease in the nitrogen intake occurs throughout pregnancy in the
guinea-pig, but at the beginning the intake is above the non-pregnant
level. Zacharjevvsky found that only four to six per cent, of the
nitrogen was unabsorbed by the human female in the last two weeks
of pregnancy, and Slemons 5 found seven per cent, and three per cent,
in a primipara and a multipara respectively at the same period. The

1 Bar and Daunay, " Bilan des echanges azotes pendant la grossesse," Jour.
de Phys. et de Path., vol. vii., 1905.

2 Kehrer, Die physiologischen und patkologucheti Beziekungen der weiblichen
Sexualorgane zum Tractus intestinalis, Berlin, 1905.

3 Ver Eeke, Lois des echanges nutritifs pendant la gestation, Bruxelles, 1901.

* Maurel, "Des depenses albuminoides pendant la grossesse chez le cobaye,"
Compt. Rend. Soc. Biol, vol. Ixi., 1907.

6 Slemons, " Metabolism during Pregnancy, Labour, and Puerperium," Johns
Hopkins Hoxp. Rep., vol. xii., 1904.

CHANGES DURING PREGNANCY 525

observations of Hoftstrom iii a primipara during the last six months
of pregnancy showed an absorption of protein, and indeed of all the
food-stuffs, as good as in the normal person. It was in fact slightly
better than the standard given by Atwater.

(6.) The Daily Requirement of Protein for the Fwtus. — The only
measure we possess of the extra protein required in pregnancy is
the amount deposited in the foetus and adnexa, the growing uterus
and mamma?. But this gives too low a figure, since 1 gm. of tissue-
protein requires more than 1 gm. of food-protein for its manufacture.
In addition, though we are dealing with a period when anabolic
processes are at a maximum in the new organism, we are bound to
assume that the cardiac, hepatic, and other activities of the foetus,
and the rhythmic contractions of the uterus, entail a certain loss of
protein from wear and tear. Whether protein substances play any
part in the provision of energy for the work of organisation is not
known. In so far as the work of organisation is carried out by
the mammalian foetus and not by the mother, the energy is probably
supplied by the combustion of carbohydrates alone (see p. 553).
Murlin has calculated in dogs the total energy requirements of the
' foetus. He finds the total metabolism per unit of weight of the
embryos three days before birth equal to three times the metabolism
of the mother dog.

The amount of nitrogenous material deposited in the human
foetus during the last stages of pregnancy has been calculated.
Michel1 estimates it at 56'69 gm. of nitrogen in two months, or
slightly under 1 gm. per day. Similar figures were obtained by
Fehling.2 Magnus-Levy's figures are somewhat lower — 50 gm. in the
last hundred days, or 0'5 gm. per day. This represents only 3 gm.
of protein, and when added to the daily deposition in the placenta,
uterus, and mamrme, it still remains relatively inconsiderable. The
calculations of Bar and of Hoffstrom have already been given in
tabular form (see p. 519).

(c.) The Nitrogen Balance in Pregnancy? — According to the earlier
investigators, a special economy of protein exists during pregnancy.
As Repreff4 puts it, anabolic processes are increased and katabolic
processes decreased in pregnancy in dogs, rabbits, and guinea-pigs.

1 Michel, " Sur la composition chimique de 1'embryon et du f<etus humain,"
Compt. Rend. Soc. BioL, vol. li., 1899.

2 Fehling, "Beitrage zur Physiologic des placentaren Stoti'wechsels," Arch,
f. Gyndk., vol. xi., 1877.

3 See also Magnus-Levy in v. Noorden's Metabolism and Practical Medicine,
vol. i., Sect. IV. D., English Translation, 1907 ; and Leo Zuntz in Oppenheitner's
Handbuch d. Biochemie, Erganzungsband, 1913.

4 • Repreff "De 1'influence de la gestation sur les echanges materiels," Rms.
Dissert., 1 888. Quoted by Siemens, Too. cit.

526 THE PHYSIOLOGY OF REPRODUCTION

Hagemami's1 investigations in the dog form the first accurate
observations of the nitrogen balance during the whole course of
pregnancy. He set himself to solve the question whether the new
organism was formed from the food, or at the expense of the maternal
tissues. From the first experiment he concluded that, even on a diet
rich in nitrogen, there was a loss of protein to the mother at the end
of pregnancy. While 33*583 gm. nitrogen were retained, the young
contained at birth 7*445 gm. This left a balance of 26*128 gm. for
the extra needs of the mother, which, he says, was nearly all required
for the formation of the fostuses (calculated at 16*6 gm.) and placentas
(8*7 gm.). The additional nitrogen required for the growth of the
uterus and mammae must have been derived from the maternal
tissues. Hence the pregnancy resulted in a loss to the mother.
Similarly, in lactation 34*056 gin. nitrogen were retained, and the
calculated excretion in the milk was 76 gm. — a loss of 41*944 gm.
nitrogen.

Later work has shown that this conclusion is not warranted, but
the figures have been given in some detail to illustrate some of the
difficulties to be overcome in carrying out the investigation. Many
troubles have been experienced in trying to keep the animals on a
constant diet, and, in addition, the increasing size of the uterus may
prove a mechanical difficulty and impede the intestinal activity
(Ver Eeke 2). Hagemann failed to obtain the shed placentas, which
were eaten by the mother animal. Hence the estimate of 8*7 gm.
nitrogen lost by them during pregnancy and labour is arbitrary, and
is, according to Bar and Daunay,3 much too high. On these
and other grounds — there is a period of thirteen days during the
pregnancy for which no data are given — the calculations for
pregnancy considered as a unit are open to objection.

On one point the results are of value. Hagemann states that the
period of gestation may be divided into two parts. In the first,
which lasts in his experiment for the first month of pregnancy, there
is a continuous loss of nitrogen to the mother each day. In the
second, there is a storage of nitrogen which is used in the growth of
the product of conception.

In Yer Eeke's experiments, nineteen in all, on the rabbit, two
phases were also frequently observed, but the results varied widely.
In some there was a positive balance throughout, and in others a
negative balance now at one time and now at another. In the

1 Hagemann, "Ueber Eiweissumsatz wahrend der Schwangerschaft uncl
Laktation," Arch. f. Anat. u. Phys., Phys. Abth., 1890; also Iiuiug.-Diss.,
Erlangen, 1891.

2 Ver Eeke, Lois des echanges nut rit if s pendant la gestation, Braxelles, 1901.

3 Bar and Daunay, " Bilan des echanges azotes pendant la grossesse," Jour,
de Phys. et de Path., vol. vii., 1905.

CHANGES DURING PREGNANCY 527

greater number the same diet was administered before and after
pregnancy and during its whole course. The amount of protein did
not far exceed the minimal requirement for the maintenance of
nitrogenous equilibrium.

Similarly, variable results were obtained by Jiigerroos1 in the
dog.2 In his Experiment II., in which the nitrogen content of the
food was high and the diet was pure flesh, there was a positive
balance each week except the second, 27'9 gm. nitrogen in all being
retained during pregnancy. In Experiment III., also on a diet of
flesh but containing only 5'97 gm. nitrogen per day, a negative
balance occurred only in the fifth and sixth weeks ; but when the
weight of the fetuses and adnexa, and a serious loss of nitrogen soon
after labour were deducted, there was a final loss to the mother
of more than 6 gm. of 'protein. In the last experiment the diet
consisted of 60 gm. of flesh and 100 gm. of sugar, which was just
sufficient to maintain nitrogenous equilibrium.3 It was maintained
for the first few days of pregnancy, and then a loss of nitrogen
occurred each week throughout the whole course of gestation except
the third.

Bar has criticised — and rightly so — the diet given by Jiigerroos
as unsiiitable. The animals did not take the food well, so that at
times there was more nitrogen in the excreta alone than in the
food. From his criticism and his own observations it is clear that
Hagem aim's dictum that gestation entails a sacrifice of protein on
the part of the maternal organism holds good only when the animal
is on an inadequate or unsuitable diet. Bar and Daunay 4 fed three
pregnant bitches on a constant diet of bread, water, fat, beef, and
salt, and estimated the nitrogen of the urine and fieces at regular
intervals. They took precautions to secure the young and the after-
births, and were able to determine accurately their nitrogenous
content. In the three animals, as in two observed by Jiigerroos, the
period of gestation was triphasic. There was first a period of
retention of nitrogen, then a balance or very slight loss, and finally a
retention increasing with the progress of gestation. Further, there
was over all a gain of nitrogen in two dogs at the conclusion of labour.
Hence they conclude that pregnancy in a healthy animal, with a
rational and sufficient diet, does not necessitate a drain on her
stock of nitrogen to satisfy the needs of the foetus.

The extensive work of Murlin on the metabolism of pregnancy
also comprises observations on the nitrogen metabolism. These

1 Jagerroos, " Der Eiweiss-, Phosphor-, und Salzumsatz wahrend der Gravid-
ita't," Arch.f. Gyniik., vol. Ixvii., 1903.

2 Jagerroos and Ver Eeke failed to secure the shed placenta?.

3 Calculated over two days only.

4 Bar and Daunay, lot:, cit. Bar, lot. cit.

528 THE PHYSIOLOGY OF REPRODUCTION

observations on four pregnant dogs, though carried out a few years
after the publication of Bar's work, were completed without any
knowledge of it. The}' led to essentially the same conclusion, namely
that pregnancy is not necessarily associated with a loss of nitrogen
by the maternal organism and does not therefore entail a sacrifice on
the part of the mother — " a sacrifice on the part of the individual for
the good of the species" — as the earlier observers had believed. On
a suitable diet the mother may actually have retained considerable
amounts of nitrogen at the end of pregnancy.- The nitrogen retention
does not, however, proceed evenly throughout pregnancy. Both in
Murlin's and in Bar's animals it was most pronounced when one
would least expect it, namely in the second half of pregnancy, when
the demands of the fostus are greatest. This increased nitrogen
retention is associated with a diminished nitrogen excretion in the
urine. In the first half of pregnancy the nitrogen retention is much
less pronounced and there may actually l>e a nitrogen loss, indicating
an increased protein katabolism.

Bar distinguishes, therefore, in the pregnant dog two distinct
periods of about equal length. The first period, when the needs of
the embryo in nitrogen are small, is characterised by a tendency to
loss of nitrogen on the part of the mother. This lasts to the middle
of pregnancy (the thirtieth day in the dog) when the second period of
distinct nitrogen retention sets in. Bar has noted further that during
the first period gastro-intestinal disturbances occur in the dog, and
has made the interesting suggestion that this period of nitrogen loss
coincides with the period of morning sickness with women. Xow in
the dog the placenta is fully matured at about the thirtieth day of
gestation, in human pregnancy it is fully developed at the end of the
fourth month. Further, Graefenberg1 has shown that the chorionic
villi of the human placenta during the first three months of pregnancy
contain a proteolytic enzyme, the seat of which he ascribes to the
Langhans cells. This ferment weakens during the fourth month and
disappears in the fifth. This, coupled with the fact that the serum of
pregnant women has a greatly increased content of anti-trypsin from
the beginning of pregnancy on, is taken to indicate that these
proteolytic enzymes pass into the maternal organism, which protects
itself by the formation of auti-ti-ypsin. It has been suggested,
therefore, that the period of protein katabolism is due to the for-
mation of proteolytic enzymes by the developing trophoblast and
the passage of these enzymes into the maternal organism. When
the placenta is full}' formed the passage of these enzymes into

1 Graefenberg, uDer Antitrypsiiigehalt de-s niiitteiiiclieu Blutserum* \v;ilirend
dei1 Schwangerschaft," Jfunc/iener med. Woc/t., vol. Ivi., 1909 ; " Beitrage zur
Physiologie der Eieinbettung," Zeitsclt. f. <:<-l>iiTt.<L. ». (/////., vol. Ixv., 1909.

CHANGES DURING PREGNANCY 529

the maternal organism ceases, and with it the increased protein
katabolism.

At present this suggestion must be looked upon as an interesting
speculation. It still remains to be shown that the introductioii of
weak proteolytic ferments produces an increased protein katabolism.
It is also obvious that gastro-intestinal disturbances must necessarily
interfere with the intake and the absorption of food, and may in
themselves be an adequate explanation of the diminished nitrogen
retention. There is, moreover, one criticism which applies to all the
metabolism experiments on pregnant dogs, with the exception of
those of Bar and Daunay. At the time when these observations
were made the existence of specific accessory food factors in nutrition —
the so-called vitamins — was not known.

One of the vitamins — the " water-soluble vitamin B " — has a
special relation to nutrition. If it is completely absent from the food
the animal loses in weight and eventually dies in a state of complete
emaciation. It has been shown recently l that this is due to an atrophy
of the. lymphoid tissue which normally plays an important part in
the absorption or assimilation of food. There is also an impairment
in the functional activity of the intestinal epithelium and of the
digestive glands leading to interference with the absorption of food.
If only very small amounts of this vitamin are present the animal
remains in good health, but an abundant supply of it has a distinctly
favourable effect on the nutritive condition. In terms of metabolism
experiments : the retention of nitrogen is dependent partly on the
amount of the water-soluble vitamin present in the diet, in the sense
that an abundant supply of this vitamin favours it. The desire to keep
the composition of the food constant in metabolism experiments has led
unintentionally to the choice of diets poor in vitamins. Thus in almost
all the experiments the diet consisted of lean meat, which is poor in the
water-soluble vitamin, either alone or with lard, which also is poor in
this vitamin, and cane sugar which does not contain any. Bar's diet,
in which bread was given with meat, was the only one which from
the point of view of vitamin-content was adequate, although by no
means ideal. And Bar's dogs showed the best nitrogen retention,
although the amount of protein given was much less than in the
experiments of those workers who had obtained a negative N balance.

In order to settle this important point of the importance of
vitamins in pregnancy, experiments have been carried out in rats.2
These were kept on a natural diet of bread, rice, and maixe, which,
though not rich in vitamins, is adequate to maintain the animals in good

1 Cramer, Drew, and Mottram, " The Function of the Lymphocyte and of
Lymphoid Tissue, in relation to Nutrition," The Lancet, 1921. "Intestinal
Absorption, Vitamins, and Radium," Brit. Jov.r. E.rp. PatfioL, 1922, vol. iii.

2 Cramer (W.), "Unpublished observations.

530 THE PHYSIOLOGY OF REPRODUCTION

health and enables them to grow and to breed. On this diet the mother
just managed to maintain its weight at the end of pregnancy. But when
this diet is supplemented by yeast preparations which are rich in the
water-soluble vitamin, then the mother always showed a considerable
gain of weight during pregnancy. The weights of the foatus were not
affected. These observations show very clearly the importance of an
abundant supply of vitamin during pregnancy for the protection of
the maternal organism. They also demand a repetition of the
metabolism experiments on dogs with an abundant supply of
vitamins in the food, before it can be accepted as definitely established
that a period of increased protein breakdown is a regular feature of
the early period of pregnancy. What can be regarded as definitely
established is the fact that the maternal organism is capable of
adapting itself to the requirements of the growing fcetus, and that this
adaptation is so efficient that the maternal organism itself gains by it.

This remarkable retention of nitrogen during pregnancy is
probably a preparation for the period of lactation. The energy
requirements of the new-born are, as Murlin showed, very- much
higher than those of the embryo immediately before birth. This is
due to the fact that the new-born has to maintain its body tempera-
ture against a colder environment. In Cramer's experiments on
rats it was found accordingly that the mother, who has to provide
for a litter of six to nine young ones, always loses in weight con-
siderably during the period of lactation, even when the diet is very
rich in vitamins. But in the latter case this loss does not exceed the
gain in weight acquired during pregnancy. On a diet more restricted
in vitamins the weight of the mother at the end of lactation was'
always considerably below that at the time of conception. These
findings suggest the possibility that in the human subject the supply
of vitamins may be a factor determining the capacity to nurse.

In the human female a nitrogen retention has been found
frequently. Most of these observations could be carried out only
during the last few weeks of pregnancy. The careful and complete
observations of Zacharjewsky x during the last few days of pregnancy
are the first contribution to the problem. He found a gain of
nitrogen of 0'873 gm. per diem in prinriparre and 5'05 gm. in
multipart. Similar results were obtained by Schrader,2 by Moris
Slemons,3 and by Hahl.4 Observations during the earlier periods of

1 Zacharjewsky, " Uber den Stickstotfwechsel wahrend der letzten Tage der
Schwangerschaft," Zeitsch. f. Bwl. N.F.. vol. xii., 1894.

2 Schrader, "Untersuchungen liber den Stoffwechsel wahrend der Schwanger-
schaft und im Wochenbett," A rch. f. (fyntil:, vol. lx., 1900

3 Slemons, loc. cit.

4 Hahl, " Beitrage zur Kenntniss des Stoffwechsels wahrend der Schwanger-
schaft," Arch. f. Gyniik., vol. Ixxv., 1905.

CHANGES DURING PREGNANCY 531

pregnancy were made by Sillevis x on three primiparte and refer to
the twenty-eighth week, the thirty-fourth week, and the thirty-
eighth week of pregnancy. In every case he found a nitrogen
retention which amounted to an average of 2 gin. per diem.
The work of Bar2 contains observations on ten women during
the end of pregnancy. Of these, nine showed a nitrogen retention
which varied from 2'26 to 7*50 gm. per diem in different individuals.
The tenth woman suffered from intestinal disturbances during
which she suffered a nitrogen loss. Some of the subjects of his
observations were examined later when not pregnant and showed
on the same diet a much smaller retention of nitrogen.

The amount of nitrogen which is used by the foetus and the
genital organs is calculated by Bar to be 1'5 gm. per diem, so that a
normal pregnant woman on an adequate diet retains more nitrogen than
is required by the foetus with adnexa, the uterus and the mammary
gland. The mother adds, therefore, to her own store of nitrogen.
For this reason Bar describes the condition of pregnancy as " une
symbiose harrnonique homogene : 1'organisme maternel fournissant au
foetus le moyen de se developper, et cela aux^seuls depens de ce qui
dans la ration deviendrait matiere excrementitielle, sans rien perdre
par consequent. Par suite de 1'adaptation de sa nutrition aux
exigences nouvelles, la mere loin d'etre lesee semble souvent utiliser
pour elle-meme une partie de ralbumine, qui lui apporte une ration,
faite d'instinct plus abondante et mieux utilisee dans 1'intestin."

The most prolonged investigation on the human subject is that of
Hoffstrom 3 who kept a primipara under continuous observation from
the sixteenth week on till the end of pregnancy. With a varied diet
he obtained the comparatively low nitrogen intake of 13 gm. per diem
on the average, with daily variations of a minimum of 10 gm. and a
maximum of 16 gm. On this diet lie obtained throughout the whole
period of observation a nitrogen retention of an average of 1*84 gm.
per diem, or fourteen per cent, of the nitrogen intake. The total
amount retained was 310 gm. N, of which 101 gm. were deviated to
the developing ovum. The maternal organism completed, therefore,
the pregnancy with the remarkable net gain of 209 gm. nitrogen.
It is equally remarkable that the body weight of the mother only
increased by 550 gm. Very similar results were obtained by
Landsberg 4 on several women. It must, therefore, be accepted as a

1 Sillevis, "Jets over de Stofwisseling cler Gravida," Akad. Porfsckrift.
Leyden, 1903. Abstracted in J/ow.. /. (jfcbut-ts/iiilfe, p. 240, 1905 ; quoted
from Bar.

2 Bar, loc. cit.

3 Hoffstrom, loc. cit.

4 Landsberg, " Untersuchungen liber den Stotfwechsel bei Schwangeren,"
Zeitsch. f. Geburtsh. u. Gynaekol., vol. Ixxi., 1912.

532 THE PHYSIOLOGY OF REPRODUCTION

fact that in pregnancy the mother retains nitrogen in amounts quite
out of proportion to its increase in body weight. In what form this
nitrogen is retained is not yet clear. The nitrogen retention does
not proceed evenly throughout pregnancy, but is most marked in the
second half of pregnancy, so that we have a confirmation of the
paradox observed by Bar in dogs that the nitrogen retention is
greatest when the requirements of the fretus are highest. The
increased retention is due to diminished excretion in the urine. It
follows, therefore, that in a normal pregnancy the maternal organism
improves its capacity for retaining nitrogenoiis material, and as wt>
shall see presently, also inorganic materials. The observations of
Hoffstrom have been confirmed by Wilson,1 who also found a retention
of nitrogen in excess of the requirements of both the fcetus and the
mammary glands and genitalia of the mother. The store of nitro-
genous material is apparently a reserve which is drawn upon and
exhausted during the puerperiuin and lactation. It has been shown
recently2 that the retention of nitrogen is associated with the
functional activity of the lymphoid tissue. If the latter is atrophied
the organism loses nitrogen and the animal emaciates. If the
lymphoid tissue is very active, there is a greatly increased nitrogen
retention. It is possible that the increased nitrogen retention in
pregnancy is associated with the leucocytosis of pregnancy which
has been observed frequently (see below, p. 556). This suggestion
finds confirmation in the observation referred to above, that a gain
in weight during pregnancy of the maternal organism can be ensured
by an abundant supply in the diet of the water-soluble vitamin
whicli stimulates the functional activity of lymphoid tissue.

(d.) The JUxcretion of Nitrogen during Pregnancy and its Distribution
in tJie Urine. — It has just been stated that the excretion of nitrogen
diminishes as pregnancy progresses. The excretion by the intestine
remained constant in Hoffstrom's case. Bar's observations on dogs
also showed that the faecal nitrogen was, if anything, diminished.
This indicates that the absorption and utilisation of food by the
intestine remains good during- a normal pregnancy. The excretion
of nitrogen by the urine is diminished, and it is by virtue of this
diminution that the maternal organism retains increasing amounts
of nitrogen. This is due to a diminished excretion of urea in the
urine, as both Bar and Murlin showed. The result is an alteration
of the nitrogen distribution in the urine : the percentage of nitrogen
excreted in the form of urea is diminished, the percentage excreted
in the form of ammonia, the so-called " ammonia index " or " ammonia

1 Wilson (K. M.), " Nitrogenous Metabolism in Pregnancy," Johns
Hasp. Evil., vol. xxvii., 1916.

* Cramer, Drew, and Mottram, loc. cit.

CHANGES DURING PREGNANCY 533

coefficient," is increased. It must be clearly understood that this
percentage increase in the ammonia nitrogen and decrease in the
urea nitrogen refer to the relative proportion of nitrogen excreted
as these two substances and riot to the absolute amounts excreted,
which are diminished. The ainino-acid nitrogen was found by
Leersum l in forty per cent, of pregnant women on the hospital diet
to amount to ten per cent, and more of the total nitrogen, whereas
it varies between 2'7 and 7*7 per cent, in the non-pregnant. Similar
high figures were obtained by Murlin. Wilson2 also found an increase
in the ammo-acid nitrogen. Polypeptides have also been observed.3
The occurrence of creatin in the urine of normal pregnant women
on a creatin-free diet \vas first demonstrated by Krause ajid Cramer 4
and confirmed by other workers.5

These facts have been the chief support of the idea referred to
above (see p. 520), that even in normal pregnancy the metabolism is
faiilty ; the high ammonia-nitrogen percentage has been interpreted
as indicating an acidosis, the high amino-acid nitrogen was taken as a
sign of hepatic insufficiency in the sense that the power of the liver to
split off ammonia from the amino-acids of the proteins was impaired.
The presence of creatin was looked upon by some authors as a confirma-
tion of the existence of hepatic insufficiency. Further confirmation
was believed to be presented by the change in the distribution of
the sulphur in the urine. The inorganic sulphate sulphur was low
in percentage like the urea nitrogen, the unoxidised or neutral
sulphur was increased.6 This was interpreted by Hoffstrom as a
diminished power of oxidation on the part of the mother. From
this point of view the toxaemias of pregnancy and eclampsia, in
which very high values for the percentage of ammonia nitrogen had
been found, appeared merely as an exaggeration of a pathological
metabolism which exists throughout pregnancy.7 In 1912 Murlin8
wrote : " This theory has obtained so firm a foothold that to-day
many obstetricians consider it an additional reason why chloroform

1 Leersum, " Die Ausscheiclung von Aniinosauren wahrend der Schwanger-
schaft," Biochem. Zeitsch., 1908, Festschr. f. Hamburger.

2 Wilson (K. M.), " Nitrogenous Metabolism in Pregnane\y ," Johns Hopkins
Hosp. Bull., vol. xxvii., 1916.

3 Falk and Hesky, "Ueber Ammoniak, Aminosauren und Peptid-Stickstoif
im Harn Gravider," Zeitsch. f. klin. Med., vol. Ixxi., 1910.

4 Krause and Cramer, "The Occurrence of Creatin in Diabetic Urine,"
Proc. Phys. Soc., Jour, of Physiol., vol. xl., 1910.

6 Van Hoogenhuyze and Doeschate, "Recherches sur les echanges organ-
iques chez les femmes enceintes," Ana. de Gyn. et (PObsMr., vol. xxxviii.,
1911.

6 Hoffstrom, loc. cit. Murlin, loc. cit.

7 Ewing and Wolf, "The Metabolism in the Toxaemia of Pregnancy," Amcr.
Jour. Obstet., vol. lv., 1907.

8 Murlin and Bailey, "Protein Metabolism in late Pregnancy and the
Puerperium," Jour. Amer. Med. Ass., vol. lix., 1912.

534 THE PHYSIOLOGY OF REPRODUCTION

should not be used as an amesthetic and its use limited in normal
labour, for it has been shown that this drug produces a degeneration
of the liver cells and therefore might prove synergistic to a condition
of toxaemia which is already present, but the symptoms of which are
latent." Examination of the nitrogen distribution in the urine was
looked upon as an important index of an impending toxemia. And
one authority went so far as to state that when the ammonia
nitrogen rose to ten per cent, of the total nitrogen and vomiting-
had been present in the early months, emptying the uterus was
indicated.

The extensive observations of Murlin l on the composition of the
urine in pregnancy, both in dogs and the human female, have thrown
doubt on this view of normal pregnancy as a pathological condition.
According to Murlin this view is based on a misconception of the
significance of the observed changes in the nitrogen distribution. He
also showed that the very high figures for the ammonia excretion in
eclampsia which have been obtained are due to the fact that in this
condition the urine has to be drawn with a catheter and that even in
the most experienced hands it is impossible to avoid introducing into
the bladder bacteria capable of decomposing the urine in the bladder.
With all the clinical signs of pre-eclampsia the nitrogen partition
may be normal up to tire development of convulsions and even during
the twenty-four hours following it. From analyses of 100 cases he
concluded that the average of the nitrogen distribution in the last
month of normal pregnancy does not markedly differ from the normal
non-pregnant condition. In individual normal cases the ammonia
nitrogen may rise to seventeen per cent, and the amino-acid unde-
termined nitrogen to. ten per cent, of the total nitrogen. But this
does not necessarily indicate an acidosis or an abnormal condition.
It is the result of the increased retention of nitrogen. In a normal
non-pregnant organism the bulk of the urea excreted represents
waste or excess nitrogen, which is split off and got rid of as urea.
During the end of pregnancy increasing amounts of this waste nitrogen
are being used up, as has been seen, by the mother for the foetus and
for its own tissues. Consequently the excretion of total nitrogen and
of urea falls and if the absolute amounts of ammonia excreted remain
unaltered, its relative amount is bound to increase, i.e. the " ammonia
index" rises. The same argument applies to the change in the
relative amounts of sulphates and neutral sulphur excreted in the
urine.

1 Murlin, "Qualitative Effects of Pregnancy on the Protein Metabolism of
the Dog," Amer. Jour. PhysioL, vol. xxviii., 1911. Murlin and Bailey, loc. cit.
Murlin, " Observations on the Protein Metabolism of Normal Pregnancy and
the Normal Puerperium," Surgery, Gyimcology and Obstetrics, 1913.

CHANGES DURING PREGNANCY 535

Murlin has pointed out that some of the high ammonia indices
obtained in eclampsia and also in normal pregnancies are due to
decomposition occurring in the bladder, when a catheter has been
used. Even with the strictest aseptic precautions it is impossible to
prevent a plug of mucus being pushed into the bladder. Catharsis is
another factor which may raise the ammonia index considerably by
temporarily lowering the nitrogen intake.

There is no doubt that in abnormal pregnancies, particularly in
the pernicious vomiting of pregnancy, there is an actual increase both
in the relative and in the absolute amounts of ammonia excreted.
The ammonia index may rise to 30, 40 and even 70 against the
normal index of 4 to 8. But this condition necessarily involves a low
nitrogen intake which may amount to starvation. This in itself
raises the ammonia index. In addition, there is frequently, if not
always, a formation of considerable amounts of aceto-acetic acid and
oxybutyric acid which lead to an increased excretion of ammonia and
thus raise the ammonia index. It has been suggested that the high
ammonia excretion is due primarily to a faulty protein metabolism
which is specific for pregnancy. But the formation of the acetone
bodies is in itself an adequate explanation of the increased ammonia
excretion, and it is difficult to understand why so many observers
refuse to attach any importance to the presence of these substances.
It is even more difficult to understand why some workers have carried
this neglect so far that they record long tables of analyses for the
nitrogen distribution of the urine which show exceptionally high
values for the ammonia index and completely omit even to test
qualitatively for the presence of the acetone bodies. The only
observations which have paid due attention to this point are those of
Gilliatt and Kennaway1 who found a close parallelism to exist
between the amount of the acetone bodies present and the ammonia
excretion. The amount of acetone bodies present in their cases was
too high to be accounted for as a direct result of starvation. The}'
are inclined to look upon the excessive formation of these bodies as
the primary cause of the condition, and draw an analogy with the
similar conditions of cyclic vomiting in children. The point is of
some practical importance, because a persistent high ammonia index
is regarded by many authorities as an indication for emptying the
uterus. The ammonia index can only be determined by a skilled
worker in a special laboratory, and for its proper appreciation requires
a knowledge of the total nitrogen intake of the patient, i.e. a collection
of the urine excreted for twenty-four hours. A good estimate of

1 Gilliatt and Keunaway, " Some Observations upon Cases of Vomiting in
Pregnancy," Quar. Jour. Medicine, vol. xii., 1918. This paper contains also a
critical survey of the literature on the metabolism in this condition.

536 THE PHYSIOLOGY OF REPRODUCTION

the amount of acetone bodies present can be obtained in a few minutes
by the proper application of Rothera's test, and a test-tube is the
only apparatus required.

Other aspects of the acid-base equilibrium during pregnancy will
be dealt with below in a separate section.

The only feature of the urine of pregnancy which could not be
explained satisfactorily by Mnrliu was the presence of creatin.
Folin, as a result of his observations on the composition of the urine
of normal adult men, had stated that on a creatin-free diet creatin is
absent from normal urine. This statement was generally accepted,
and the excretion of creatin in the urine was therefore taken as a
sign of an abnormal metabolism, and far-reaching speculations were
based on it. These speculations were deprived of their basis, at least
so far as pregnancy is concerned, when it was found that normal
women frequently and children always excrete creatin, even when on
a creatin-free diet.1

Post-par turn there is a rise in the excretion of total nitrogen
which is independent of the food. It occurs rather suddenly at about
the sixth or seventh day. There is also an increase in the excretion
of creatin. These changes are probably related, as Murlin suggests,
to the involution of the uterus.

The albuminuria of pregnancy in the human female is not strictly
physiological. .Regarding its frequency very varying figures have
been given, ranging from five per cent, to sixty per cent. It appears
in the second half of pregnancy, gradually increases up to the time of
birth, and quickly decreases in the puerperium. In fifty per cent,
of the cases it has already disappeared on the fourth day after labour.
The protein is of renal origin, and in a typical case amounts to O'Ol
to 0'05 per cent. That it is not due to mechanical pressure on the
renal vessels or ureter, or to increased intra-abdominal pressure
seems certain. Xor has any definite proof been given of the influence
of a toxin arising in the fostus, and causing degeneration of the renal
epithelium, Veit 2 explains it by his hypothesis of the presence of
placental constituents in the maternal circulation. Metabolic
investigations in pregnancy complicated by albuminuria show nothing
characteristic (Magnus-Levy 3).

A special constituent of the urine may be found during' the
puerperium. Thougli called peptone (Fischel 4), it really consists of

1 Krause and Cramer, "Sex and Metabolism," Proc.'Phys. Soc., Jour, of
Phi/siul., vol. xlii., 1911. Krause, "On the Urine of Women under Normal
Conditions, etc.," Quar. Jour. E.rp. Phys., vol. iv., 1911. Krause, "On Age
and Metabolism and on the Significance of the Excretion of Creatin," ibia.,
vol. vii., 1913.

2 Veit, "Ueber Albuminurie in der Schwangerschaft," Berlin kiin. Tlor//., 1920.

3 Magnus-Levy, see v. Noorden, loc. cit.

4 Fischel, " Peptongehalt der Lochien," Arch. f. (>i/nak., vols. xxiv. and xxvi.

CHANGES DURING PREGNANCY 537

deutero-albumoses which arise from the involution, i.e. autolysis,
of the uterus (Langstein and Neubauer x). As with similar proteins
introduced subcutaneously, the organism has not the power of
splitting them up, and they are excreted unchanged. Fischel stated
that peptonuria might also occur in pregnancy ; but this was
disproved by Thomson,2 who also showed that a puerperal peptonuria
did not regularly exist. Ehrstrom 3 regards it as a certain indication
of fever and sepsis, the peptone being contained in the leucocytes of
the purulent lochia.

D. The Carbohydrate Metabolism, in Pregnancy

(a.) The Absolution of Carbohydrates by the Mother. — The starch
digestion is said to be retarded in the stomach during pregnancy
(Kehrer4). Little is known regarding the absorption of carbo-
hydrates, but there is evidence of a tendency to abortion in certain
animals on a diet containing them in excess (see p. 522).

(b.) Carbohydrates of the Maternal Organism. — Lactose may appear
in the blood in pregnancy as well as during the lactation period.
Ltevulose is not present in the serum of a healthy animal ; but it is
normally present in the allantoic fluid of the cow (Giirber and
Griinbaum 5), and in the blood-serum of the foetal rabbit, cow, and
sheep (Paton °). Whether it is the only monosaccharide present has
not yet been determined, but it is in sufficient amount to render the
serum Isevo-rotatory. The proof that the carbohydrate is la-vulose
rests on the lievo-rotation of the plane of polarised light and the
ketone reaction. Doubts have recently been expressed regarding
the sufficiency of these two tests.

The glycogen store of the liver is stated to be increased in
pregnancy in the dog (Burlando "), in the guinea-pig (Maurel 8), and

1 Langstein and Neubauer, " Autolyse des puerperalen Uterus," Munch, mod.
Woch., 1902.

- Thomson (H.), " Ueber Peptonurie in der Schwangerschaft und im
Wochenbett," Deutsche mcd. Woc/t., 1889.

3 Ehrstroni, "Puerperale Peptonurie," Arch. f. Gytiiik., vol. Ixiii., 1901.

* Kehrer, Die physiologischen wnd pathologischcn Bi'-ziehungcn dvf vwiltlinhen
Sexucdorgann zum Tractus Intestinalis, Berlin, 1905.

5 Giirber and Griinbaum, " Ueber das Yorkommen von Lavulose im Frucht-
wasser," Munch, ined. Woc/i., 1904.

0 Paton, Watson (B. P.), and Kerr, "On the Source of the Amniotic and
Allantoic Fluids in Mammals," Trans. Roy. 8oc. Edin., vol. xlvi., 1907.

~ Burlando, " Behaviour of Hepatic Glycogen during Menstruation,
Pregnancy, Puerperium, and Lactation Period," Arch. ItoL di (linec., 1906.

8 Maurel, " Des depenses albuminoides jiendant la grossesse chez le cobaye,"
Compt. Rend. Soc. Biol., vol. Ixi., 1907.

538 THE PHYSIOLOGY OF REPRODUCTION

in the human female (Charrin and Guillemont 1). But since the
amount of glycogen varies greatly and is dependent to a large extent
on the diet, it is difficult to establish with certainty that there
is an increase. Harding,2 on the other hand, postulates a greater
tendency to a deficiency of glycogen in the maternal liver and
associates this deficiency with the morning sickness of women and
even with pernicious vomiting. This view is based on the work of
Bohr and of Lochhead and Cramer,3 who showed that the presence
of the fetal cells imposes a special demand for carbohydrates on the
maternal organism. The pregnant woman has therefore a greater
tendency to pass into a state of specific carbohydrate starvation
than the nan-pregnant woman. The important practical application
of this fact will be discussed in greater detail below (see p. 544).

The placenta contains glycogen in amounts which vary greatly in
different species.3 It is found only in traces in Ruminants, but
in great amount in Rodents (see Chapter X., p. 460). It occurs
also at the margin of the zonary placenta in Carnivores, and in the
human placenta. In many species it has not yet been investigated.

In the foetus, the feature of the glycogen is not its high
percentage, but its almost universal distribution in the developing
tissues.4 It has been shown by Bohr that the energy in the
mammalian foetus is supplied by the combustion of carbohydrates
(see p. 553), and by the wide distribution of glycogen an available
supply is procured in every part of the foetal body in which the work
of organisation is proceeding.

(c.) Thi' Daily Requirement of Carbohydrate for the Foetus. — Some
idea can be obtained of the daily requirements of glycogen for the
fetus of the rabbit in the second half of pregnancy. The appended
table, from the paper of Lochhead and Cramer,5 gives the amount of
glycogen contained in the unborn young from the eighteenth day
of gestation till the day before parturition.

The table shows that 1*2 gin. of glycogen are deposited between
the eighteenth and the twenty-eighth day, or about 0*2 gm. per fetus.
Hence the average daily deposition is 0'02 gm. per fetus. In the later
stages the rate of deposition increases out of proportion. This is due
to the assumption of its glycogenie function by the fetal liver.

1 Charriu and Guillemont, " Physiologie pathologic ^ue de la Grossesse/'
Compt. Rend. 8oc. ttiol., 1899.

2 Harding, "Nausea and Vomiting in Pregnancy," The Lancet, vol. ccl., 1921.
:! Lochhead and Cramer, " The Glycogenie Changes in the Placenta and the

Ftetus of the Pregnant Rabbit," Proa. Roy. Soc. Londvn, B., vol. Ixxx., 1908.

4 Gierke, "Glycogen in der Morphologie des Zellstoffwechsels," ffabi/it(iti<>/>*-
scJirift, Freiburg, 1905.

5 Lochhead and Cramer, " The Glycogenie Changes in the Placenta and the
Fo?tus of the Pregnant Rabbit," Pr<><: lt<>,/. Soc. London, Ser. B., vol. Ixxx., 1908.

CHANGES DURING PREGNANCY

539

Day of

Gestation.

Average Weight
of each Foetus
in Grammes.

Average Amount
of Glycogen
per Foetus.

Number of
Foetuses.

Total Amount
of Glycogen.

18

0-89

•0018

8

•0144

20

2-32

•0050

6

•0300

21

3-28 -0080

5

•0400

22

4-13 .

•0103

4

•0412

23

7-20 -0203

8

•1624

24

9-75 '0346

6

•2076

25

20-23 '0808

7

•5656

26

H'24 -0257

5

•1285

27

32-84 -1418

3

•4254

28

32-07 -2017

6

1-2102

29

26-67

•1199

9

T0791

TABLE to show the foetal weight and amount of foetal glycogen in the second
half of pregnancy (rabbit). In the animal killed at the twenty-sixth day,
the pregnancy was abnormal, one foetus being dead and the others badly
developed. In the last also the foetuses were unusually small.

The amount of carbohydrate oxidised each day can be calculated
from Bohr's figures. The oxygen consumption for a foetus weighing
30 gm. is 0-14 c.c. per minute. This is sufficient to oxidise O'OOOIT
gin. of sugar, or 0'245 gin. per day, which is equal to 0'227 gm. of
glycogen. Hence for six fretuses, the average number, 1/362 gm. are
required for combustion each day. In addition, an average of
0'3 gm. of glycogen is deposited in them daily near the end of
pregnancy. Hence the total daily requirement for the unborn young
at this stage is 1'662 gm. of glycogen. A small additional amount of
carbohydrate is required for the daily increasing blood-serum, for the
liquor amnii in the rabbit, and for the manufacture of mucin and
other glycoproteins.

(d.) Excretion of Carbohydrates in Pregnancy : (rlt/eosuria and
Lactosuria. — Blot1 was the first to postulate the occurrence of a
" physiological glycosuria " in pregnancy. Kirsten - found sugar in
the urine in the majority of cases of pregnancy and labour, and
regularly in the puerperium. Hofmeister3 first discussed the
relationship of the glycosuria to milk secretion, and proved that
the sugar excreted in the puerperium was lactose.4 The sugar is
in extremely small amounts, but above the normal. Leinaire 5 found

1 Blot, " De la glycosurie physiologique chez les femmes en couches, etc.,"
Compt. Rend. *S'oc. Biol., vol. xliii., 1856.

2 Kirsten, " Ueber das Vorkommen von Zucker im Harn der Schwangeren,"
Monatsschr. f. (jrebnrtsh. u. Frauenkmnkh., vol. ix., 1857.

;! Hofmeister, " Ueber Laktosurie," Zeitsch. f. physiol. Chem., vol. i., 1877.

4 Corroborated by Kaltenbach (" Die Laktosurie der Wochnerinnen," Zeitsch.
f. Geburtsh. u. Gynak., vol. iv.) and many others.

5 Lemaire, " Ueber das Vorkommen von Milchzucker," Zeitsch. f. physiol.
Chem., vol. xxi., 1895.

540 THE PHYSIOLOGY OF REPRODUCTION

O'OOo to 0'009 per cent., and Brocard1 an upper limit of O'Ol per
cent. Zacharjewsky,2 however, observed no increase in the reducing
power of the urine on an ordinary diet during the last weeks of
pregnancy. The first definite increase comes with the appearance
of lactose in the urine after birth, though it may also be excreted a
few days before birth. It is more evident when the milk is not
utilised and becomes re-absorbed, but it rarely exceeds 0'3 per cent.3
Extirpation of the mammary glands immediately stops the lactosuria,4
and, if carried out in pregnancy, prevents it.5 In 2200 consecutive
cases Cron ° found sixty-eight, or three per cent, of pregnant women
whose urine gave a test for the presence of some reducing sugar;
seventeen women gave a positive reaction during the puerperium.
Cron points out that the presence of a reducing sugar during
pregnancy or the puerperium is usually due to lactosuria or to
alimentary glycosuria, and this condition must be distinguished from
diabetes mellitus and other types of glycosuria. He estimates that
•'50 '50 per cent, of pregnant women may at some time or another
present an alimentary glycosuria.

Numerous observations7 on the blood sugar during normal
pregnancy fail to show any deviation from the normal in women.
In rabbits Schirokauer 8 believes to have noted an increase ; in two
bitches Oppler and Rona9 failed to find any difference before and
after they had littered. During labour the blood sugar rises and
falls again in the puerperium. Very high values were found in
eclampsia if the blood was taken immediately after a convulsion.
This suggests that the hyperglycremia of labour is related to the
increased activity of the muscles.

The glycosuria of pregnancy has been ascribed to a diminished

1 Brocard, " La Glycosurie de la Grossesse," These de Pan's, 1898.

2 Zacharjewsky, loc. cit., Zeitsch. f. Biol., vol. xxx., 1894.

3 The inability of the organism to oxidise lactose was demonstrated by Voit
(" Verhalten der Zuckerarten im menschlichen Organismus," Deut. Arch. f. klin.
Med., vol. Iviii., 1897).

4 Sin6ty, "Urine of Guinea-Pigs in Puerperium," Ctnnpt. Rend, >Soc. Biot.,
vol. 1.

5 V. Noorden, loc. cit., vol. i. (see also pp. 602-605).

6 Cron, "Glycosuria during Pregnancy," Amer. Jour. Obst. and Gyncec.,
vol. i., 1920.

7 Benthin, "Der Blutzuckergehalt in der Schwangerschaft, in der Geburt,
im Wochenbett und bei Eklampsie," Zeitsch. f. Geburtsh. v. Gyndk., vol. Ixix.,
1911. Neubauer and Novack, "Zur Frage der Adrenal inaemie und des
Blutzuckers in der Schwangerschaft," Deutsche med. Witch., 1911. Bergsma,
" Der Zuckerstotfwechsel in der Schwaugerschaft," Zeitsch. f. Geburtsh. n. Gyniik.,
vol. lxxii.,'1912. Ryser, "Blutzucker wahrend der Schwangerschaft," Deutsch.
Arch.f. klin. Med., 1916.

8 Schirokauer, "Zum Zuckerstoffwechsel in der Schwangerschaft," Berl. kiln.
Woc.h., 1912.

9 Oppler and Rona, " Untersuchungen tiber den Blutzucker," Biochem. Zeitsch.,
vol. xiii., 1908.

CHANGES DURING PREGNANCY 541

glycolysis (Brocard) and to hepatic insufficiency (Cristalli),1 without
sufficient evidence. The greater tendency to alimentary glycosuria
in pregnancy was upheld by Lanz,2 who observed it after the
administration of 100 gin. of glucose. It was confirmed by
Payer,3 Keichenstein,4 and Bergsma.5 In his observations on
partially paricreatectomised dogs Allen ° found a slight lowering of
the limit of carbohydrate assimilation during pregnancy. These
observations are difficult to interpret, because, as we shall see in
dealing with the fat metabolism, the pregnant organism requires
a larger amount of carbohydrate than the non-pregnant organism
to keep the metabolism normal as judged by the tendency to the
excretion of the acetone bodies.

E. The Metabolism of Fats in Pregnancy

(a.) TJie Absorption of Fats by the Mother. — The absorption of fats
from the intestine is increased during pregnancy (Ferroni7), the
neutral fats, fatty acids, cholesterin, and soaps contained in the fteces
being all decreased towards the end of the gestation period. This
is the time when the subcutaneous tissues of the foatus receive an
abundant supply. They rapidly reach the normal level in the
puerperium. There is a corresponding increase of fat in the maternal
blood in the dog and guinea-pig, and the excess disappears after
parturition (Capaldi).8

(&.) Fats of the Maternal Organism. — According to Miotti,9 the liver
cells contain a continuously increasing amount of fat, first in the
central parts of the lobule and later throughout. He looks on it as
a fatty infiltration, and concludes that an increased fat formation
takes places during pregnancy. This observation has been confirmed
by Mottram,10 who compares it to the fatty infiltration of the liver

1 Cristalli, Ricerche sidla presenza dMo zuchero nelle orine delle donne gravide
e puerpere, Naples, 1 900. ^

2 Lanz, "Ueber alimentare Glykosurie bei Graviden," Wiei&med. Presse, 1895.

3 Payer, " Einfluss des Zuckers auf den Stott'wechsel dt^r Schwangeren,1'
Monatsschr. f. (Jelmrtsh. u. (ri/nak., vol. x., 1899.

4 Reichenstein, " Glycosurie und Schwangerschaft," Wiener klin. Wochenschr.,
1909; ibid., 1911.

5 Bergsma, loc. cit.

6 Allen, "The Influence of Pregnancy upon Experimental Diabetes," A ma:
Jour. Physiol., vol. liv., 1920.

7 Ferroni, "I grassi neutri . . . delle gravide e delle puerpere sane," Ann.
di Ost. e Ginec., 1905.

8 Capaldi, "Sul contenuto di grasso del sangue nella gravidanza e nel
puerperio," di Ann. Ost. e Ginec. , 1905.

8 Miotti, " Contributo allo studio istologico de f egato durante la gravidanza,"
Ann. di Ost. e (jlinec , 1900.

10 Mottram and Coope, " Fatty Acid Infiltration of the Liver during
Pregnancy and Lactation," Jour. Physiol., vol. xlix., 1914.

542 THE PHYSIOLOGY OF REPRODUCTION

which occurs in hunger. This " physiological " infiltration is duo
to a mobilisation of fat from the depots. It passes first to the liver
where it is desaturated and then passes On to the tissues.

A very significant change in the metabolism of fats — using the
term fat here to include lipoids — is the great increase in cholesterin
and cholesterinesters in the blood during pregnancy. There is also
an increase in the true fats (glycerinesters) but not in the phos-
phorised fats (lecithin). This was first recognised by Herrmann and
Neumann l and has been confirmed by many workers. There is an
associated increase in the storage of these substances in the corpora
lutea and in the adrenal cortex. The blood of the foetus contains
always less cholesterin than the maternal blood and does not contain
any cholesterinesters at all. The hyper-cholesterinujmia of the
mother diminishes towards the end of pregnancy and with the
beginning of lactation : there is an outpouring of these substances
in the milk. It is found accordingly that the hypercholesterinsemia
passes off more quickly in mothers who suckle their children than
in those who do not. The bile of the mother is also richer in
cholesterin, and according to M'Nee 2 this may account for the more
frequent occurrence of gall-stones in women. The function of
cholesterin is not definitely known, although there is no lack of
speculation concerning it. The meaning of this hypercholesteringemia
of pregnancy is therefore not yet understood.

In the placenta there is evidence of a transmission of fat to the
product of conception. Even in the early stages of pregnancy the cells
of the uterine mucosa are infiltrated with fat, and the trophoblast is
pervaded with fat globules. In Ungulates a large amount of fat
is contained in the uterine milk (see p. 435). In those mammalian
orders in which the trophoblast is directly bathed by maternal blood,
the fat dissolved in it forms a second available supply. There is no
reason to doubt an active transference of fat from the mother, or
to assume that a transformation from carbohydrates or proteins is
necessary. ~

(c.) The Daily Requirement of Fat for the Fcetus. — The daily require-
ment of fat varies very considerably during pregnancy, and especially
towards the end, when the subcutaneous fat of the foDtus is deposited.
Fehling 3 found O5 per cent, of fat in the human foatus at the fourth
month, over four per cent, at the eighth, and nine per cent, at the

1 Herrmann and Neumann, " Uber die Lipoide der Gravidita't, etc.,"
klin. Wockenschrift, vol. xxv., 1912.

2 M'Nee, " Cholesterin : An Account of its Relations to Pathology and
Physiology," Quar. Jour. Medieinc, vol. vii., 1914. This paper contain.-, a
complete bibliography up to 1914.

3 Fehling, "Beitrage zur Physiologie des placentaren Stott'verkehrs,' .\ /•<•/>.
f. Gyniil;., vol. xi., 1877.

CHANGES DURING PREGNANCY 543

ninth month. In guinea-pigs the foetal liver contains considerable
amounts of fat, especially towards the end of gestation.1 This excess
of fat, which is less saturated than connective tissue fat, disappears
during the first two or three days after birth.

(d.) Origin of the Foetal Fat. — As to its origin, Thiemich - states
that it is not derived from the alimentary fat of the mother, since
after feeding a dog in two successive pregnancies on widely different
fats, palmin and linseed oil, he could determine no difference in the
constitution of the foetal fat. Oshiuia 3 comes to the same conclusion
from his investigations on the number of ultra-microscopic particles
in the blood of cats, rabbits, and guinea-pigs. He states that the
number is dependent on the stage of development, and independent
of the condition of the mother's blood — for example, when a great
increase is produced by rich fat-feeding. Capaldi, on the other hand,
states that the percentage of fat is the same in the maternal and
foetal blood, at least afc the end of pregnancy. Some feeding experi-
ments carried out by Hofbauer4 agree with this. He administered
coco-nut oil, which consists essentially of the triglycerides of laurinic
and myristinic acids with a very small quantity of tripalmitin, to
three pregnant guinea-pigs, and demonstrated laurinic acid in con-
siderable amount in the foetuses. Hence the fat of the food, or at
least one of its fatty acids, had been transmitted across the placenta.
But any conclusions based on the introduction of a foreign fat must
be guarded.

In the fretus, fat is present in many of the tissues in a state of
fine division. Its widespread distribution and its amount, probably
equal at least to that of glycogen, are a characteristic of foetal life ;
but its significance is not obvious if, as Bohr states, it is not a source
of energy. Guillot 5 showed that it did become a source of energy
immediately after birth, when the fcetus is faced suddenly with
the necessity to maintain its bod}' temperature against a lower
external temperature. The rapid disappearance of fat from the
foetal liver, observed by Imrie immediately after birth, also suggests
such an explanation, although Imrie himself suggests that the fat in
the foetal liver is destined for the connective tissue depots. He found
twelve per cent, of fat in the lungs of foetuses dying during labour,
and only six per cent, after several hours' respiration. Fat may have

1 Imrie and Graham, " The Fat Content of Embryonic Livers," Jinn:
Chem., vol. xliv., 1920.

- Thiemich, "Ueber die Herkunft des fotalen .Fettes," Crntmlbl. f. Phys.,
vol. xii., 1898.

* Oshima, '' Ueber das Vorkoninien von ultra-mikroscopischen Teilchen im
fotalen Blute," Ccntralbl. f. Phys., vol. xxi., 1907.

4 Hofbauer, Kio(ogie der mewcMiehen Plazeiita, Wien and Leipzig, 1905.

5 Guillot, quoted in Richet:s Dictionnaire d<' Phyxiiilogie, Ai'ticle " F<etus."

544 THE PHYSIOLOGY OF REPRODUCTION

anabolic functions to perform in the building up of the foetal body,
e.g. in the synthesis of lecithin.

(f.) Disturbances of Fat Metabolism in Pregnancy. The Excretion of
the Acetone Bodies. — The " acetone bodies " — aceto-acetic acid and
/3-oxybutyric acid — are intermediate products of the oxidation of the
fatty acids. Acetone is formed from them by further decomposition.
They are formed normally, and very small amounts are excreted in
the urine of normal persons, while the bulk is further oxidised to C02
and H20. Vicarelli l was the first to observe the presence of these
bodies in the urine of pregnant women. He attributed it to the
presence of a dead fostus, a conclusion which was disproved by Menu
and Mercier,2 who found it to be present when the foatus was living,
but when the pregnancy was abnormal in other respects (albuminuria,
eclampsia). Stolz,3 and later Bar,4 found acetone also in a number of
normal pregnancies. In order to appreciate the findings and con-
clusions of the older observers it is necessary to remember that the
tests they had at their disposal were not very delicate and gave
positive results only when considerable amounts were present. A
second factor of importance in interpreting their findings is the diet.
In the normal organism the appearance of the acetone bodies in the
urine is related to the diet, in the sense that the excretion is greatly
increased when carbohydrates are withheld from the diet, and also of
course when no food at all is taken. This is supposed to be due to a
greatly increased formation of these substances when the liver has
lost its glycogen and has to draw upon fats and protein for the forma-
tion of carbohydrate. According to some authorities it is due to a'
deficient oxidation which allows these substances to escape in the urine
before they are burnt up. Forges and Novack 5 made the important
observation that in normal pregnant women the acetone bodies can
always be made to appear in the urine by keeping them for one day
on a special diet which does not lead to an increased excretion in
normal non-pregnant women. This diet was poor in carbohydrates
but by no means carbohydrate free. Conversely they could suppress
the excretion of these substances by adding carbohydrate to the diet.
With a more delicate test for the acetone bodies (Rothera's test)
Harding6 has recently confirmecl these results. He makes the

I Vicarelli, "Die Acetonurie wahrend der Schwangerschaft," Pragcr /«< /.
Wo,-/iens<:/ir., 1893.

- Menu and Mercier, Ihdletin de la Sw. fffObstetrique fie Pat-is, 1898.

3 Stolz, "Die Acetonurie in der Schwangerschaft, Geburt tind im Wochen-
bett," Arck.f. (,'y>i., vol. Ixv., 1902.

4 Bar, Lew/is de Pathologic Qbit&ricale, p. 822, 1907.

•' Forges and Novack, "TJber die Ursache der Acetonurie bei Schwangeren,"
Bert. klin. Work., vol. xlviii., ii.r 1911.

II Harding, tm: i-it.

CHANGES DURING PREGNANCY 545

interesting suggestion that the nausea and vomiting of early
pregnancy is related to this abnormal metabolic condition and can be
combated by an abundant supply of carbohydrates given at frequent
intervals. It is certainly suggestive that the "morning sickness"
occurs at that time of the day when there has been the longest
interval after a meal. This tendency of the normal pregnant organism
to acetonuria suggests further that at least some forms of the
pernicious vomiting of pregnancy, where large amounts of the acetone
bodies are excreted, are merely an aggravation, due to some toxic
factor, of this normal tendency. For we know from the occurrence
of the acetonuria following after chloroform or ether narcosis or in
some febrile conditions that some toxins are capable of inducing this
metabolic disturbance.

The work of Bohr and of Lochhead and Cramer has shown the
importance of carbohydrates for the development of the fostus, in
Rodents at any rate. The facts referred to in this section indicate
that this holds good also for the human foetus. Pregnancy in the
human subject imposes such a drain of carbohydrate material from
the mother that for the maintenance of a normal metabolism a larger
supply of carbohydrate is necessary for the pregnant than for the
non-pregnant woman.

The formation of these acid bodies in pregnancy naturally leads
to a discussion of the acid-base equilibrium in pregnancy.

F. The Acid-base Equilibrium in Pregnancy. The so-called
" Acidosis of Pregnancy"

The question to be discussed here is whether the acid-base
equilibrium is disturbed in normal pregnancy by the excessive
formation of acid metabolites. The body tends to maintain at a
constant level the reaction of the blood or, as it is called, the
hydrogen-ion concentration of the blood. It can compensate for an
increased formation of acid bodies chiefly by the following three
methods : firstly, by an increased lung ventilation which leads to a
lowering of the alveolar C0.2 pressure ; secondly, by a transformation
of the disodium phosphate excreted in the urine into the acid mono-
sodium phosphate ; and thirdly, by combining acid with ammonia,
which would visually be converted into urea, and excreting the
ammonium salt in the urine. The criteria of an increased formation
of acid metabolites — a condition which is now usually designated
by the term " acidosis " — are therefore lowering of the alveolar CO.,,
the acidity of the urine, and the increased excretion of ammonia.
These three factors do not necessarily come into play simultaneously.
It should be also borne in mind that the conception of " acidosis " as
18

546 THE PHYSIOLOGY OF REPRODUCTION

defined by these criteria is rather different from the conception of
acidosis as used by the older writers, who applied it to conditions
where abnormal acids such as aceto-acetic acid and oxybutyric acid
can be definitely identified, as, for instance, in the acidosis of diabetes
or of pernicious vomiting of pregnancy (see above, p. 544). In this
latter condition there is," as has been shown above, a greatly increased
excretion of ammonia in the urine for which, no doubt, the factor
of starvation is largely responsible, while the alveolar C02 shows
only a comparatively slight diminution, as Loosee and van Slyke l
point out. In normal pregnancies the observations of Hasselbalch
and Gamrneltoft 2 have shown that there is a slight but distinct fall in
the alveolar C02 pressure. This fall was observed in one case very
early in pregnancy, namely on the first occasion when menstruation
ceased, and gradually progressed to 30 mm. against a normal value
varying between 35 mm. and 43 mm. In another case the alveolar
C02 pressure before birth was 32 mm. and rose to a mean value of
38 mm. after birth.

Hasselbalch also holds that the ammonia excretion is slightly
increased in pregnancy, although as Murlin has pointed out (see
above, p. 534) the argument as to the existence of an acidosis from
the increased ammonia excretion is open to criticism.

There is also a distinct diminution in the C02 combining power
of the blood : the so-called " alkali reserve " of the blood. Thus
Siemens 3 found in normal pregnancies values of 37 c.c. to 50 c.c. C02
per 100 c.c. of plasma against values from 55 c.c. to 75 c.c. for normal
non-pregnant women. The toxaemias of pregnancy show the same
apparent paradox with reference to the alkali reserve as they do
with the alveolar C02 : the diminution of the alkali reserve in these
conditions is no greater than in normal pregnancies, while the
ammonia index gives very high figures.

If we accept the definition of acidosis as an increased formation
of acid metabolites as evidenced by a fall in the alveolar C02 pressure,
then pregnancy is accompanied by an acidosis. This "acidosis" does not,
however, affect the reaction of the blood, which is stated to be normal.
It is not yet clear how this acidosis is related to the acidosis of the
pernicious vomiting of pregnancy, in which the main alteration of
the acid-base equilibrium is an increased excretion of ammonia with
only a slight change in the alveolar C02 pressure. The " acidosis " of

1 Loosee and van Slyke, "The Toxaemias of Pregnancy," Aimer. Jour. Med.
Sciences, vol. cliii., 1917.

2 Hasselbalch and Gammeltoft, " Neutralitatsregulation des graviden
Organismus," Bwchem. Zeitsch.., vol. Ixviii., 1915 ; 'ibid., vol. Ixxiv., 1916.

3 Slemons, "Analysis of the Blood in Eclampsia and Allied Conditions,"
A me): Jour. Obstet., vol. Ixxvii., 1918. See also Emge, "Acidosis in Normal
Uterine Pregnancies," Amer. Jour. Obstet., vol. Ixxiv., 1916 ; vol. Ixxvii., 1918.

CHANGES DURING PREGNANCY 547

normal pregnancy, which leads to an increased lung ventilation, may
be a physiological method by which the maternal organism adapts
itself to the presence of the foetus with its increased demand for
oxygen and its increased formation of C02.

G. The Metabolism of Metals and Salts in Pregnancy

Little is known regarding the metabolism of the individual
metals and salts. The fixation of mineral elements is slight at the
beginning, but becomes active towards the end of pregnancy. From
first to last, about a hundred grammes are transferred from the
mother to the human foetus. With a few exceptions, the mineral
salts are approximately in the same proportion throughout pregnancy.
The exceptions are sodium, potassium, and calcium, of which sodium
decreases and calcium increases with the replacement of cartilage by
bone, and potassium increases with the increased manufacture of red
blood corpuscles (Hugounenq x).

The analyses of Oamerer and Soldener 2 of the ash of the human
foetus have given the following results : —

P2O5 CaO NagO K2O MgO Fe2O3 Cl
38-5 36-1 9-1 7'8 0'9 0'8 77

The significance of these figures lies in the preponderance of CaO
and P205 m tne asn- The analyses of Michel 3 and of Fehling 4 of
embryos at different stages of development show that the retention
of mineral salts by the foetus does not proceed evenly. There is a
sudden increase, beginning in the twenty-ninth week, in the retention
of calcium from 0'4 gm. to 2 gm. and of phosphorus from 0'3 gm.
to 1*3 gm. These relations have been expressed very clearly in
graphs by Hoffstrom.5 The relatively high retention of iron is also
significant.

(a.) Iron. — Part at least of the iron for the foetus is derived from
the hsemoglobin of the maternal organism. In the poly-cotyledonary
placenta of Ruminants and the zonary placenta of Carnivores, the
disintegration of red blood corpuscles has been demonstrated. There
is less certainty regarding the actual ingestion of the red cells by the
syncytium of the discoid placenta, though it has been described by

1 Hugounenq, "Recherches sur la statique des elements mineraux et
particulierement du fer chez le foetus humain," Compt. Rend. >Soc. Biol., llth
series, vol. i., 1889.

2 Camerer and Soldener, "Die chemische Zusammensetzung des neugeborenen
Menschen," Zeitsch. f. Biol., vol. xxv., 1902.

3 Michel, "Sut la composition de 1'embrion et du foetus humain aux
differents epoques de la grossesse," Compt. Rend, de la Soc. de Siol., vol. li., 1899.

* Fehling, "Beitrage zur Phys. des placentaren Stoffverkehrs," Zeitsch. f.
Gynakol., vol. ii.

6 Hoffstrom, loc. cit.

•

548 THE PHYSIOLOGY OF REPRODUCTION

Peters in an early human ovum.1 But in all placentae yet investigated,
iron-containing granules have been observed in the trophoblast. The
possible sources are haemoglobin, which is in part absorbed as such
by the trophoblast in man (Bonnet2), nucleoprotein, and the reserve
iron of the mother. Nuclein is the only iron-containing constituent
of yolk of egg, and must serve for the manufacture of haemoglobin
in the developing chick. It is also known that in the adult organism
nucleoprotein is a better source of iron for haemoglobin than any
inorganic or other organic compound hitherto administered by the
mouth.3 Hence it is not difficult to conceive that the same process
may occur in the foetus. But whether it is the food nucleoproteins
or the organised nuclein bodies of the maternal organism that are
utilised, is unknown.4 With regard to the reserve iron of the
mother, it is stated by Charrin5 that the store in the spleen is
reduced during pregnancy.

In the foetus iron is required for the synthesis of haemoglobin
(see p. 505) and nucleoproteins.6 But large amounts of iron are also
stored in the liver and other organs of the embryo without being
used immediately. According to Bunge's 7 law, this forms a reserve
which is drawn on after birth to make up for the deficiency of the
iron in the milk. Thus the liver of a rabbit contains 18 mg. of iron
per 100 gm. body-weight at birth, and only 3'2 mg. twenty-four days
later. This fact is of great practical importance in the nutrition of
infants. The period during which milk is an adequate diet for the
infant is limited by the reserve of iron which the infant has stored
away in its body before birth. This reserve is sufficient to last during
the normal period of lactation. Then a mixed diet, containing food
richer in iron than milk, is required. If the mother during pregnancy
is kept on a diet rich in iron, the embryo will store more iron than
when the diet is poor in iron. If the supply of iron t*> the mother is
kept low during repeated pregnancies abortion may occur.8

1 See Chapter X., p. 505.
a Ibid.

3 V. Noorden, loc. cit., vol. i., p. 78.

4 As the purine bases of the urine are stated to be decreased in pregnancy,
the maternal nucleins are probably not a source of iron for the foetus to any
Appreciable extent.

5 Charrin, " Physiologic pathologique de la grossesse," Compt. Rend. Xoc. de
Hiol., 1899.

6 The nucleoproteins of the fetal placenta in the sheep differ in their
•chemical constitution from those of the maternal placenta. They are probably
.synthesised in the ovum from lower complexes, in the same way as the nucleo-
proteins of the chick embryo are built up though the egg contains no
purine bases.

7 Bunge, " Weitere Untersuchungen iiber die Aufnahme des Eisens in den
Organismus des Sauglings," Zcitsch.f. physiol. C/iem., vols. xvi. and xvii., 1892-93.

8 Fetzer, " Experimentelle Untersuchungen iiber den Eisenstoffwechsel,"
•26 Kongress f. inn. Medizin, ] 909.

CHANGES DURING PREGNANCY 549

According to Veit and Scholten,1 the villi can dissolve intact red
cells of the circulating blood, just as the solution of erythrocytes can.
be produced by placental extracts. As a result of this, luemo-
globinsemia may occur in pregnancy. Wychgel 2 observed it in eight-
out of twenty-three pregnancies, and the condition occurs more
frequently still in eclampsia. At present, however, it is not yet
generally accepted that an erythrotoxin is formed by the syncytium,
though Bonnet3 has shown histologically that a destruction of red
cells probably takes place during life. He noticed on the surface of
the villi " perfect and damaged erythrocytes in all stages of degenera-
tion, clumping and solution." So Hofbauer found, by adding neutral-
red to the chorionic villi of two fresh two-months' placentae teased in
saline, that many of the blood corpuscles showed red dots indicating
degeneration.

(b.) Calcium. — The great demand for calcium by the developing
embryo, especially during the last three months of pregnancy, would
lead one to suppose that pregnancy involves a loss of calcium on the
part of the mother. It has, in fact, been stated that teeth are apt to
become brittle in pregnancy from a decrease in calcium fluoride-
and a deficiency in enamel formation.4 Evidence of a special
drain on calcium is also found in puerperal osteomalacia, which
occurs in poor people who presumably live on an ill-constructed
diet, and which has been produced experimentally as the result
of such a diet in animals.5 The effect on the teeth is not admitted
as a general occurrence in pregnancy by some authorities,6 if it
occurs at all, and is probably the result of a diet deficient in calcium.
The exact observations of Hoffstrom have shown clearly that on a
suitable calcium-rich diet the mother actually gains in calcium. On
such a diet Hoffstrom's patient retained 34*3 gin. Ca during the whole
pregnancy, of which 30*1 gm. were required by the foetus, so that the
mother ended her pregnancy with a net gain of 4'2 gin. Ca. As has
been stated, the requirements of the foetus are particular!}' high
during the last three months of pregnancy, and the mother responds
to this increased call for calcium by diminishing the excretion of
calcium in the urine and to a lesser extent by the intestine. Even
on this diet and with a total positive balance there are short periods of

1 Veit and Scholten, " Synzytiolyse und Hamolyse," Zeitsck. f. Gcburtsh. v.
Gynal'., vol. xlix.

- Wychgel, " Untersuchungen viber das Pigment der Haut und der Urin
wahrend der Schwangerschaft," Zeitsch. f. Gelmrtsh. u. Gyncik., vol. xlvii.

3 Bonnet, quoted by Hofbauer (Biologic der menschfichen Plazenta, Wien und
Leipzig, 1905).
. 4 Terrier, " De 1'influence de la grossesse sur les dents," These de Paris, 1899.

5 Stilling and Mering, "Ueber experimentelle Erzeugung von Osteomalacie,"
Zentralbl. f. med. Wissenschaft, 1889.

0 Dr. Sim Wallace, Private communication.

550 THE PHYSIOLOGY OF REPRODUCTION

a loss of calcium. This occurred particularly at the end of the sixth
month (thirtieth week) when there was a sudden increase in the foetal
requirements of Ca. It is necessary to emphasise a point in
Hoffstrom's observations, the importance of which has not been
sufficiently recognised, namely the nature of the diet on which
Hoffstrom's patient lived. She was allowed a free choice of food
and from a sample menu given in Hoffstrom's paper it is clear that
the diet was particularly rich in calcium. She consumed a litre of
milk a day in addition to other calcium-rich foods and the result is
an average weekly intake of Ca of 1*7 gm. throughout the whole of
pregnancy. Tigerstedt calculates that the amount of Ca necessary to
maintain a normal non-pregnant organism does not exceed 1 gm. Ca
per week. When the diet is poor in calcium, as in the experiments
of Dibbelt l on a pregnant bitch, the embryos do not suffer a loss of
calcium. The deficiency is made up entirely by the maternal tissues,
which in Dibbelt's experiments had to furnish 4'2 gm. Ca. The calcium
content of the blood is said to be increased during pregnancy.2 These
considerations emphasise the importance of including in the dietary
of pregnant women food material rich in calcium such as milk, butter,
cheese, green vegetables, certain fruits such as oranges, lemons, etc.
With reference to this point it is important to note that margarine is
practically free from calcium, while butter is a food particularly rich
in calcium.

(c.) Magnesium. — The magnesium intake and output was also
observed by Hoffstrom. The amounts which came into question are
much smaller and the results are irregular. On the whole there is a
magnesium retention amounting on an average to 0'013 gm. per day
with an average daily intake of 0'282 gm. which Hoffstrom considers
to be low. There are periods of magnesium loss. But even with
this low intake Hoffstrom's case retained during the whole of
pregnancy a total of 2-44 gm., of which 0*98 gm. was fixed by the
foetus, so that the maternal organism gained.

(d.) Phosphorus. — The phosphorus metabolism runs as a rule
parallel to the nitrogen metabolism. The same has been observed in
pregnancy (V. Eeke,3 Schrader4). Jagerroos,5 however, showed an
equilibrium between intake and output of phosphorus in a pregnant
dog which showed a distinct loss of nitrogen. But since sucli

1 Dibbelt, "Die Bedeutung der Kalksalze f. d. Schwangerschaft und Still-
periode, etc.," Ziegler's Seitr. path. Anat., vol. xlviii., 1910.

2 Lamers, "Der Kalkgehalt des menschlichen Blutes, etc.,!' Zeitsch.j. Oeburtsh.
u. Gynak., vol. Ixxi., 1912.

3 Ver Eeke, loc. tit.

* Schrader, " Stoffwechsel wahrend der Schwangerschaft," Arch. f. Gyn&k.,
vol. lx., 1900.

5 Jagerroos, loc. cit.

CHANGES DURING PREGNANCY 551

abnormalities have also been observed in normal persons (Ehrstroin l)
it cannot be considered as being peculiar to pregnancy. In
Hoffstrom's case 2 there was an increased phosphorus retention, which
was associated with a diminished excretion of phosphates in the urine
and resembled in that respect the progressive nitrogen retention.
But the nitrogen was retained somewhat more actively than the
phosphorus, so that there was no strict parallelism. Altogether
56 gm. of phosphorus were retained during pregnancy, of which
18 gm. were fixed by the foetus, so that the maternal organism
showed a net gain of 38 gm. Similar results have been obtained by
Bar 3 and by Landsberg.4

(e.) Sulphur. — Hoffstrom's observations are, as he himself states,
not conclusive, because the analyses for the sulphur intake were
vitiated by an error. . His analyses of the excreted sulphur show a
progressive diminution of the total sulphur which is due entirely to
a diminution of the so-called " oxidised sulphur," the sulphur excreted
in the various kinds of sulphates. The so-called " neutral sulphur,"
which is derived mainly from cystin and from the taurin of the bile,
showed actually an increase. The relative proportion of neutral
sulphur to oxidised sulphur, which is supposed to be about 1 : 5 in a
normal person, was in Hoffstrom's cases completely changed and was
1 : 2. Bar found a much higher excretion of total sulphur with
a relation of neutral sulphur to oxidised sulphur of 1 : 9. Landsberg
has been able to demonstrate a sulphur retention during the end of
pregnancy which was proportionate to the nitrogen retention.
Hoffstrom interprets the diminution of the oxidised sulphur in his
case as indicating a diminished store of bases in the body, while the
increase in the neutral, i.e. unoxidised sulphur, he interprets as being
due to a diminished power of oxidation on the part of the pregnant
organism. Murlin, however, has pointed out that this change in the
sulphur excretion can be explained as being the result of the progressive
sulphur retention, just as in the case of nitrogen.

(/.) Chlorides. — The first estimations of the chlorides of the urine
in pregnancy indicated no variation from the non-pregnant level
(Winckel5). Repeated investigations have been carried out since
the discovery that a retention of chlorides may occur in nephritis
and lead to oedema ( Widal 6).

1 Ehrstroin, "Zur Kenntniss des Phosphorumsatzes bei dem erwachsenen
Menschen," Skandin. Arch. f. Physiol., vol. xiv., 1903.

2 Hoffstrom, loc. cit.

3 Bar, loc. cit.

4 Landsberg, loc. cit.

5 Winckel, Studien ilber Stoffwechsel etc., Rostock, 1865.

6 Widal, " La cure de d6chloruration dans le mal de Bright," Arch. Gener.,
vol. cxciii., 1904.

552 THE PHYSIOLOGY OF REPRODUCTION

Biancardi 1 stated that cedemas in pregnancy were sometimes due
to the same cause, and might be cured by decreasing the chlorides
of the food. Next Cramer2 affirmed that all cases of hydrops
graviditatis without albuminuria were due to a retention of sodium
chloride; and Boni, whose careful investigations of the urine in
pregnancy have already been referred to, found that the chlorine
excretion was decreased, and remained low during the puerperium.
Along with this there is a retention of water to maintain osmotic
balance. Normally 90 to 100 per cent, of the water taken in is
excreted in the urine, but the percentage fell to 72 per cent, in a
primipara, 53 per cent, in a multipara, and 48 per cent, in a twin
pregnancy (Siemens 3). Such a retention did not occur in a woman
who was later delivered of dead twins, 93 per cent, of the water
being excreted in the urine.

Birnbaum's 4 results are not in agreement with the others. He
states that a retention of chlorides occurs only in the nephritis of
pregnancy, and not in normal pregnancy or in hydrops without
albuminuria. In the blood-serum the chlorides were 0'1740 per
cent, and 0'1775 per cent, in two cases, and 01733 per cent, in a
non-pregnant woman.

H. Respiratory Exchange and Energy Metabolism during Pregnancy

Modifications in the respiratory exchange arise from the altera-
tions in the maternal organism, and from the requirements of the
product of conception. To a certain extent diffusion of oxygen takes
place from mother to foetus, as it has been proved, by experiments
in asphyxia of the mother, that the direction in which oxygen goes
across the placenta depends on the tension. Whether there is also
a gas-secretion by the trophoblast is unknown.

With regard to the foetus, Pfliiger argued on theoretical grounds
that the oxidation processes were inconsiderable, and the oxygen
intake small. Experimentally Cohnstein and N. Zuntz 5 arrived at
a similar conclusion. More recently, however, Bohr6 has shown
that in the later stages of pregnancy the foetal guinea-pig has a
respiratory exchange at least as high as the mother. The actual

1 Biancardi, " Sulla cura declorurante nelle nefriti e nelle albuminurie nel
campo ostetrico," Ann. di Ost. c Ginec., 1906.

2 Cramer, " Chlornatrium-Entziehung bei Hydrops Graviditatis," Monats-
-ift f. Geburtsh. u. Gyniik., vol. xxiii.

3 Siemens, "Metabolism during Pregnancy, Labour, and Puerperium," Johns
Hopkins Hasp. Rep., vol. xii., 1904.

4 Birnbaum, "Excretion of Chlorides during Pregnancy," Arch. f. Gynak.y
vol. Ixxxiii., 1907.

5 Cohnstein and Zuntz, " Untersuchungen iiber das Blut, den Kreislauf, und
die Atmung beim Saugetierfotus," Pflitgcr>s Arch., vol. xxxiv., 1884.

6 Bohr, " Der Respiratorische Stoffwechsel des Saugetierembryos," Skandzn.
A, -c.lt. f. PhysioL, vol. x., 1900.

CHANGES DURING PREGNANCY 553

figures per kilo per hour which he obtained were 462 c.c. C02 for
the mother and 509 c.c. C02 for the foatus. The difference
between these figures is within the rather high limits of error in
such a complicated experiment. He has also shown that the foetal
respiratory quotient is unity, indicating that carbohydrates are the
source of energy. The same has been found in new-born puppies
before suckling (Murlin 1). Russell and Gye 2 determined the oxygen
consumption of embryonic mouse tissue by suspending the minced
tissue in blood and analysing the blood in Barcroft's apparatus.
They found values much lower than those obtained for normal adult
tissues under the same conditions. Their results are therefore more
in accord with Pfliiger's conception. Russell and Woglom 3 in subse-
quent observations determined the respiratory quotient of minced
embryonic tissue (skin) and found it to be unity. It is well to
remember that all these experiments refer only to the foetus in the
later stages of development, and that they entirely leave out of
account the placental metabolism. In the later stages there is a
wide distribution of glycogen throughout the tissues of the fcetus,
and the fcetal liver has assumed its glycogenic function. It is
scarcely justifiable to extend Bohr's results to the early stages of
pregnancy, when the placenta prbbably takes a leading part in
embryonic development. It may be that at that time also glycogen
is the source of energy for the placenta in Rodents, but it cannot
be so in Ruminants. In their placentae glycogen is found only in
traces, while fat is in considerable amount. Hence we must not assume
that in Ruminants the energy is derived from the combustion of
carbohydrates until experimental evidence has been obtained.

With regard to the total energy exchange the older investigations
of Oddi and Vicarelli4 showed a progressive increase in the con-
sumption of oxygen during the last third of pregnancy in rats ; but
Magnus-Levy raises the objection that the movements of the animals
were not restricted. The observations of Magnus-Levy,5 F. Miiller,6
and L. Zuntz7 showed that in the human pregnancy there was

1 Murlin, "Protein Metabolism in Development," Amer. Jour, of Physiol.,
vol. xxiii., 1908-09.

2 Russell and Gye, "The Oxygen Consumption of Mouse Tissue," British
Jour. Exp. Paikol., vol. i., 1920.

3 Russell and Woglom, "The Respiratory Exchange of Surviving Mouse
Tissues, etc.," ibid., vol. i., 1920.

4 Oddi and Vicarelli, "Influence de la grossesse sur 1'echange respiratoire,"
Arch. ital. de Biol., vol. xv., 1891.

5 Magnus-Levy, " Stoffwechsel und Nahrungsbedarf in der Schwangerschaft,"
Vortrag, Zeitsch. f. Geburtsh. u. Gynak., vol. lii., 1904 ; also v. Noorden, loc. cit.,
vol. i.

6 F. Miiller, "Diskussion zum Vortrag von Magnus-Levy," see v. Noorden,
loc. cit., vol. i.

7 Zuntz (L.), " Der Stoffaustausch zwischen Mutter und Frucht," Ergebn. d.
Phys., 1908.

18 A

554 THE PHYSIOLOGY OF REPRODUCTION

certainly no decrease in metabolism, the metabolic changes being at
least as active in the fostus as in the mother.

L. Zuntz's1 more recent and extended observations on women
before and during pregnancy showed a distinct increase in the
energy metabolism, which became progressively greater towards
the end of pregnancy. At the same time he observed, from the
middle of pregnancy on, as Magnus-Levy had before him, an
increased lung ventilation. This fact is of interest as it indicates
a stimulation of the respiratory centre by acid metabolites, in other
words, it is an expression of an acidosis (see p. 545). The increased
muscular work involved in this increased lung ventilation accounts
for at least part of the higher values obtained for the gaseous
exchange. If a corresponding amount is deducted there still remains
a slight increase in the gaseous metabolism which is on the whole
proportional to the increase in weight. In one case there was an
increase out of proportion to the increase in weight. Carpenter and
Murlin 2 have made very complete observations on pregnant women
during the last few days of pregnancy in a respiration calorimeter.
Unfortunately they could not obtain observations on the same
individuals in the non-pregnant state and were therefore restricted
to comparing their results on pregnant women with observations on
eight other normal women. They found an increase in the energy
exchange which was four per cent, higher than could be accounted
for by the increase in weight. Their measurements gave an energy
requirement for the resting pregnant woman during the end of
pregnancy of 24 cal. per day and per kilo. This must be regarded
as a minimum value. Hoffstrorn's case had an intake of 31 cal. per
day per kilo.

In a dog pregnant with one puppy Murlin 3 found a very marked
increase in the total energy production amounting to nine per cent,
which became apparent in the sixth week and persisted till the end
of pregnancy (ninth week). The same dog became pregnant again
with five puppies. The increase then was much greater and was
exactly proportional to the greater weight of the offspring. In
comparing these results with those obtained in women the greater
weight of the puppy embryos in proportion to that of the mother
must be borne in mind.

1 Zuntz (L.), " Respiratorische Stoffwechsel u. Atmung wahrend der
Graviditat," Arch. f. (Jynakol., vol. xc., 1910.

2 Carpenter and Murlin, "The Energy Metabolism of Mother arid Child just
before and just after Birth," Arch, of Int. Med., vol. viL, 1911.

3 Murlin, "Energy Metabolism of the Pregnant Dog," Ainer. Jour. PhysioL,
vol. xxvi., 1910.

CHANGES DURING PREGNANCY 555

I. Summary of Clwnges in the Metabolism of Pregnancy

The maternal organism adapts itself to the progressively increasing
requirements of the foetus, which dominate the metabolism of the
mother. Under suitable dietary conditions this adaptation is so suc-
cessful that the maternal organism completes pregnancy with a gain.
The dietary conditions which must be observed more particularly are
an abundant supply of firstly carbohydrates, secondly calcium, and
thirdly vitamins. The gain at the end of pregnancy is a reserve for
the mother to draw upon during the puerperium and lactation.
Under unsuitable dietary conditions the mother suffers first.

The adaptation of the maternal organism involves changes in the
metabolism of the mother, of which the most definitely established i&
the occurrence of an acidosis due probably to the slightly increased
formation of aceto-acetic acid and oxybutyric acids. Under normal
conditions this acidosis remains within physiological limits and, like
the acidosis which sets in as the result of exposure to high altitudes,
it subserves the function of increasing the ventilation of the lungs.
Many facts point to the maternal liver as the organ on which
pregnancy imposes a special strain and this is confirmed by a hyper-
trophy of this organ occurring in pregnancy.1 But no clear evidence
has yet been brought that normal pregnancy involves a hepatic
insufficiency.

K. Analogy between the Metabolism of Pregnant Animals and
Tumour- Bearing Anim als

Certain changes in the maternal organism, for instance those due
to the changes in the mamma and uterus, are obviously specific to
pregnancy. Others, however, are apparently simply the result of the
presence of a mass of rapidly growing cells in an adult organism.
For as Cramer 2 has pointed out, the metabolism of tumour- bearing
animals presents a close similarity to that of pregnant animals.
There is in both cases an increased nitrogen retention 3 which is in
excess of that necessary for the mass of growing cells and thus
benefits the organism serving as a host. There is the same faculty in
both cancerous cells and embryonic cells of being able to build up
living protoplasm with less nitrogen than the non-growing or more
slowly growing cells of the adult host. There is an increased demand

1 Herring, "The Effect of Pregnancy upon the Size and Weight of some
of the Organs of the Body," Brit. Med. Jour., llth December 1920.

2 Cramer, "Zur Btochemie des Wachstums," VIII. Interned. Physiologen
Konqress, Vienna, 1910. Also ///. Sci. Report, Imperial Cancer Research Fund,
19u8.

3 Cramer and Pringle, " Contributions to the Biochemistry of Growth," Proc*
Roy. Soc., B., vol. Ixxxii., 1910 ; vol. Ixxxvi., 1912.

556 THE PHYSIOLOGY OF REPRODUCTION

for carbohydrates which suggests that carbohydrate material is
essential for growth.1 There is further the hypertrophy of the liver
which has been observed in tumour-bearing animals 2 as in pregnant
animals.3 This close analogy suggests that perhaps the physiological
acidosis of pregnancy may occur in cancer, and that the diminished
C02 pressure in the alveolar air, which is such a very early indication
of this acidosis in pregnancy, might also be found comparatively early
in cancer.

III. THE CHANGES IN THE MATERNAL TISSUES DURING PREGNANCY

The changes in the ovaries, the mammae, and the mucous
membrane of the uterus are dealt with elsewhere. To the changes in
some of the other organs, a brief consideration is here given.

(a.) The Blood. — -Ehrlich's4 statement that pregnancy does not
appreciably alter the number of the red blood corpuscles has been
more or less firmly established by Ingerslev,5 'Dubner,6 Bernhard 7
and others in man, by Spiegelberg and Gscheidlen 8 in the dog, and
by Cohnstein9 in the sheep. Their investigations have upset the
older theory of a hydrse.mia of pregnancy.

There is evidence of a slight increase of haemoglobin (Payer,10
Fehling,11 Winckeluianri,12 Wild13), especially towards the end of
pregnancy.

The number of leucocytes increases during pregnancy, and there
is a further rise during the act of parturition (Nasse,14 Lebedeff,15
Rieder10). The leucocytosis is referred by some to the lymphoid

1 Cramer and Lochhead, "Contributions to the Biochemistry of Growth,"
Proc. Roy. Soc., vol. Ixxxvi., 1913.

2 Medigreceanu, " Ueber die Grosseverhaltnisse einiger der wichtigsten
Organe bei Tumortragenden Ratten u. Mausen," Berl. klin. Wochenschrift, 1910.

3 Herring, loc. cit.

4 Ehrlich, " Die Anamien," in Nothnagel's Spezielle Pathologic.

5 Ingerslev, " Ueber die Menge der roten Blutkorperchen bei Schwangeren,"
Centralbl. f. Gyndk., 1879.

6 Dubner, " Untersuchungen iiber den Hamoglobingehalt des Blutes, etc.,"
Miinch. med. Woch., 1890.

7 Bernhard, " Untersuchungen iiber Hamoglobingehalt und Blutkorper-
chenzahl in der letzten Zeit der Schwangerschaft," Miinch. med. Woch., 1892.

8 Spiegelberg and Gscheidlen, "Untersuchungen iiber die Blutmenge
trachtiger Hunde," Arch.f. Geburtsh. u. Gyndk., vol. iv.

9 Cohnstein, " Blutveranderungen wahrend der Schwangerschaft," PJliigers
Arch., vol. xxxiv., 1884.

10 Payer, vide v. Winckel's Handbuch der Geburtshiilfe, v.ol. i., H. 1.

11 Fehling, "Ueber Blutbeschaflenheit, etc.," Arch.f. Gyndk., vol. xxviii., 1886.

12 Winckelmann, " Hamoglobin-Bestimmungen bei Schwangeren und Woch-
nerinnen," Inaua. Diss., Heidelberg, 1888.

13 Wild, " Untersuchungen iiber den Hamoglobingehalt und die Anzahl der
roten und weissen Blutkorperchen bei Schwangeren," Arch.f. Gyntik., vol. liii.

14 Nasse, Das Blut, Bonn, 1836.

15 Lebedeff, quoted in v. Winckel's Handbuch der Geburtshiilfe, vol. i., H. 1.

16 Bieder, Beitrdge zur Kenntnis der Leukocytose und verwandter Zustande des
Blutes, Leipzig, 1892.

CHANGES DURING PREGNANCY 557

tissue of the endometriuni, and by others to an increase in the groups
of lymphatic glands in the neighbourhood of the genital apparatus.
The spleen is not obviously affected, but a remarkable change was
observed in rats in the thymus. It was reduced to half its normal
size and histologically presented the appearances of involution.
These findings confirm the view expressed above that the functional
activity of the lymphoid tissue is of special importance during the
period of pregnancy.

According to Spiegelberg and Gscheidlen, the total amount of
blood is increased during pregnancy in the dog from 7 '8 per cent, to
9 per cent, of the body-weight. There is no essential difference in
the specific gravity (Nasse, Blumreich x). The reaction of the blood
has been dealt with above (see p. 546).

(b.} The Heart and Circulation. — Older authorities stated that a
true hypertrophy of the heart occurred during pregnancy, and was
caused by the increased length and size of the uterine vessels, the
placental circulation, and the compression of the aorta by the gravid
uterus. Experiments showed, however, that the uterine vessels did
not offer a resistance which required an increase in the work of the
heart (Engstrom 2), while the compression of the abdominal aorta and
the introduction of large quantities of fluid into the abdominal cavity
prodiiced no change which could be detected from the pulse
(Heinricius 3). The controversy has been a long one, but it does not
properly belong to this article. In the rat Herring 4 failed to find a
hypertrophy or enlargement as the result of pregnancy.

It has been suggested that the increased work of the heart is
due to an increased peripheral resistance from the presence of a
vaso-constricting substance in the blood. Whether such a substance
exists is very doubtful. The investigation of extracts of the placenta
by Lochhead and Cramer5 in 1907, proved that this organ contained
no blood-pressure raising substance. The substances extracted by
Dixon and Taylor6 from the placenta and observed to have an
adrenalin-like action, were subsequently shown to arise in the course
of putrefaction.

The blood-pressure is not affected in normal pregnancy, but is
always raised in labour as a result of the uterine contractions. After

1 Blumreich, " Der Einfluss der Graviditat auf die Blutalkalescenz," Arch. f.
Gyncik., vol. lix., 1899.

2 Engstrom, " L'Influence de la grossesse sur la circulation," Arch, de Gyn.,
vol. ii., 1886.

3 Heinricius, Experimentelle und klinische Untersuchungen ilber Circulations-
verhalten der Mutter und der Frucht, Helsingfors, 1889.

4 Herring, "The Effect of Pregnancy, etc.," British Med. Jour., llth December
1920.

6 Lochhead and Cramer, Unpublished observations.

6 Dixon and Taylor, " On the Physiological Action of the Placenta," Proc.
Roy. Soc. Med., London, vol. i., 1908.

558 THE PHYSIOLOGY OF REPRODUCTION

'parturition the pressure falls, but rises again on the third day of the
puerperium.

The effects of pregnancy in the human female on the heart have
l>een the subject of a recent monograph,1 to which the reader is
referred for details. So far as the normal heart is concerned the
effepts may be summarised as follows: There is no change in the
circulation during the first months of pregnancy. After the sixth
month the response to effort is restricted: breathlessness appears
after an effort which can be accomplished in comfort by a normal
non-pregnant woman. There is no hypertrophy of the left ventricle.
Owing to the displacement of the abdominal viscera the shape of
the chest is altered, so that there is a displacement of the heart.
The apex beat may be pushed out one inch beyond the left nipple
line, and this has led to the erroneous supposition of the occurrence
of a hypertrophy. Similarly an increased area of dullness to the
right of the sternum can usually be made out.2 This also is due to
the abnormal position of the heart, and is not to be interpreted as
a dilatation of the right ventricle. There is venous stasis, probably
due to pressure on the pelvic veins, and a tendency to dropsy, the
cause of which is not clear.

Varices of the lower extremities and external genitals are frequent
in human pregnancy. They are clue mainly to the increased intra-
abdominal pressure and the stretching of the abdominal wall.
Secondary thromboses are common in the puerperium.

(c.) The Ductless Glands. — There is regularly a swelling of. the
thyroid gland in pregnancy (Tait 3), which consists of a simple hyper-
trophy, and not a vascular engorgement or cystic change (Freund 4).
It has been shown experimentally in cats that a remnant of the gland,
which is sufficient to maintain health in the non-pregnant state, is
insufficient after the onset of pregnancy (Lange5). Herring's6
observations on pregnant rats show no increase in size and no
histological changes indicating an increase of secretion. The adrenals,
however, showed a slight increase in weight and the load of adrenalin
was slightly higher. The hypercholesterinsemia of pregnancy seems
to suggest that there are probably functional changes in the
adrenal cortex. The pituitary body of pregnant rats is diminished in
size by about twenty-four per cent. This diminution affects mainly
the glandular lobe, which shows a great diminution of the granular
eosinophil cells. The human pituitary is stated to be enlarged in

1 Mackenzie (Sir J.), Heart Disease and Pregnancy, London, 1921.

2 v. Winckel, Handbuch der Geburtshiilfe, vol. i.

3 Tait, "Enlargement of the Thyroid Body in Pregnancy," Obstet. Jour., 1875.

4 Freund, " Ueber die Beziehung der Schilddriise, etc.," Deuts. Zeitsch. f.
Chir., vol. xxxi., 1890.

5 Lange, " Die Beziehungen der Schilddriise zur Sehwangerschaft,"
f. Geburtsh. u. Gynak., vol. xl., 1899.

0 Herring, loc. cit.

CHANGES DURING PREGNANCY 559

pregnancy, and the eosinophil cells of the glandular lobe are then
replaced by large neutrophil cells.1

(W.) The Skin.— The cause of the increased pigmentation of the
skin in pregnancy is little understood. It has been looked on as a
simple deposit of pigment, as the result of infection with the Microsporon
furfur, the cause of pityriasis versicolor which not infrequently
attacks pregnant women, and as a subcutaneous haemorrhage.'2
Jeannin3 first suggested that it was derived from haemoglobin set
free by the solution of red blood corpuscles. According to Veit 4 the
haemolysis may be produced by the circulation of syncytial elements
in the blood. The presence of iron in the pigment, though strongly
denied by Truzzi,5 has recently been demonstrated by Wychgel.0 He
associates its presence with the frequent occurrence of hsemoglobinuria
in pregnancy. V. Fiirth and Schneider's suggestion that the pigment
is derived from tyrosin by the action of a placental tyrosinase is
mentioned elsewhere (Chapter X., p. 507).

An abnormal development of the hair of the face and body is
occasionally seen in pregnancy (Slocum,7 Halban 8). Under the name
of dermographismus, Freund9 describes a phenomenon, often met
with in pregnancy, similar to the tachc cerebrate of meningitis and
other nervous affections. It may be elicited even in the early stages
of gestation, and is best shown by stroking the skin over the sternum
or fundus uteri.

(#.) The Mammcc.— The growth of the mammary glands is brought
about by the development of new vesicles, the widening of existing
blood-channels, and the formation of new vessels.10 Even in the first
half 9f pregnancy, and sometimes in the first weeks, the mamm;e
contain colostrum, a milky fluid composed of proteins, albumen,
globulin, and casein, the carbohydrate lactose, fat, free fatty acids,
lecithin, cholesterin, free glycero-phosphoric acid, and urea (Winter-
stein and Stickler n).

1 Erdheim and Stuiume, Ubcr die ^ckwangerschaftseerdiulerung der
Ziegler, Bcitr. z. pathol. Anat., vol. xlvi., 1909.

2 See v. Winckel's Handbuch der (jeburtsltidfe, vol. i., H. 1.

3 Jeannin, "Observations pour sei-vir a 1'histoire du masque des femmes
enceintes," (laz. Hebdoni., 1868.

4 Veit and Scholten, " Synzytiolyse und Hamolyse," Zeitsch. f. Geburtsh. n.
</?/««&., vol. xlix., 1903.

•"' Truzzi, "Ueber die Genese der Hyperchromie der Haut in der Graviditat,"
Monattschr, f. Gebwrteh., vol. xi., 1898.

6 Wychgel, " Untersuchungen iiber das Pigment der Haut und den Urin
wahrend der Schwangerschaft," Zeitsch. f. (leburtsh. u. Gyncik., vol. xlvii.

7 Slocum, "Hair Development in Pregnancy," New York ^fed. Rec., 1875.

8 Halban, "Zur Frage der Graviditatshypertrichose," Wien. klin. Woc/t., 1907.

9 Freund, "Die Haut bei Schwangeren," Verhandl. d. VI. deutsch.Dennatolog<'n-
Kongr. zu Strassburg.

10 See Chapter XIII.

11 Winterstein and Stickler, " Die chemische Zusammensetzung des Colos-
trums," Zeitsch. f. physiol. Chem., vol. xlvii., 1906.

CHAPTER XII

THE INNERVATION OF THE FEMALE GENERATIVE
ORGANS — UTERINE CONTRACTION — PARTURI-
TION—THE PUERPERAL STATE

" Birth is the end of that time when we really knew our business, and the
beginning of the days wherein we know not what we would do, or do."—
SAMUEL BUTLER.

THE innervation of the generative organs of the male was dealt with
at some length in an earlier part of this work. It remains in the
present chapter to describe the nerve supply to the female generative
system, and more particularly to the uterus, since this is the organ
which is especially concerned in the process of parturition. But
before giving an account of the innervation of the internal organs,
the nerve supply to the vulva and clitoris may be briefly dealt -with.

THE INNERVATION OF THE EXTERNAL GENERATIVE ORGANS

The external generative organs in the female are similarly
innervated to those of the male (p. 265 et seq.).

Langley and Anderson l found that stimulation of the first five
lumbar nerves in the cat, or the third, fourth, and fifth lumbar
nerves in the rabbit, produced the same effects as in the male
excepting that they were less pronounced. The effects were (1)
Pallor of the clitoris and of the mucous membrane of the vulva,
accompanied by slight retraction of the clitoris, (2) Contraction of
the vulva, and (3) Contraction of the muscles of the adjoining skin,
drawing the vulva dorsally towards the rectum.

Langley,2 and subsequently Langley and Anderson,3 found that
two groups of effects, which were antagonistic to one another, could
be produced by stimulating the sacral set of nerves in the vertebral
canal, but that, as in the male, only those fibres which exercised an
inhibitory influence run from the spinal cord in the sacral nerve
roots. The inhibitory effects produced were (1) Flushing of the

1 Langley and Anderson, "The Innervation of the Pelvic and Adjoining
Viscera," Jour, of Physiol., vol. xix., 1895.

2 Langley, " The Innervation of the Pelvic Viscera," Proc. Phys. 3oc., Jour,
of Physiol., vol. xii., 1891.

3 Langley and Anderson, loc. cit.

56°

INNERVATION OF THE GENERATIVE ORGANS 561

vulva and clitoris, (2) Dilatation of the vulva, and (3) Relaxation of
the skin muscles surrounding the vulva. The visceral motor effects
were the same as those produced by the lumbar set of nerves as
described above. Besides these effects, contraction was induced in
the external sphincter of the vagina and in the striated genital
muscles.

THE INNERVATION OF THE OVARIES

The ovary is innervated from the sympathetic plexus accompany-
ing the ovarian artery and from the plexus associated with the
ovarian branch of the uterine artery. It is generally supposed that
the nerve fibres, which are non-medullated, are merely vascular in
function.1 The fact that ovulation in some animals only occurs as
a consequence of coition, and then takes place at a definite time
afterwards, points to the conclusion that the follicles discharge in
response to a stimulus conveyed to the ovary by its nerves (see
p. 129). It has been suggested that the rupture is due to the
stimulation of erectile tissue.2 Nerve fibres have been described in
the tissue immediately surrounding the follicles, and have even been
traced as far as the follicular epithelium.

THE INNERVATION OF THE UTERUS AND VAGINA AND THE
MECHANISM OF UTERINE CONTRACTION

'It is well known that the onset of parturition is manifested by
rhythmically repeated contractions of the uterus which constitute
the "labour pains." But although the contractions are most pro-
nounced at this period, observations on animals have shown that
even in a virgin uterus rhythmical movements may occur.

Kehrer 3 showed long ago that a uterus separated from the body
is capable of undergoing ^contractions if kept moist, and at the
normal body temperature. More recently Helme,4 Kurdinowski,5

1 Von Herff, " Ueber den f eineren Verlauf der Nerven im Eierstocke des
Menschens," Zeitsch. f. Geburt. w. Gyndk., vol. xxiv., 1892. Gawronsky,
" Ueber Verbreitung und Endigungen der Nerven in den weiblichen Geni-
talien," Arch. f. Gyndk., vol. xlvii., 1894. Kallius, " Nervendigungen in
Driiseri d. Eierstocke," Merkel and Bonnet's Ergeb. d. Anat. u. Entivick.,
vol. iv., 1895. Mandl, " Ueber Anordnung und Endigungsweise der Nerven
im Ovarium," Arch. f. Gyndk., vol. xlviii., 1894-95. Vallet, "Nerfs d'Ovarie,
etc.," Thesis, Paris, 1900. Abel and Mcllroy, "Nerves of the Ovary," Phys.
Soc., 5th June 1909. See also references on p. 358.

2 Eouget, " Eecherches sur les Organes Erectiles de la Femme," Jour, de la
Phys., vol. i., 1858.

3 Kehrer, " Zusammenziehungen der glatten Genitalmuskelatur, etc.,"
Beitrdge zur Vergl. u. Exper. Geburtskunde, 1867.

4 Helme, " Contributions to the Physiology of the Uterus and the Physio-
logical Action of Drugs upon it," Reports of the Laboratory of the Royal College
of Physicians, Edinburgh, vol. iii., 1891.

6 Kurdinowski, " Physiologische und pharmakologische Versuche an der
isolirten Gebarmutter," Arch. f. Anat. u. Phys., Phys. Abth. (supplement), 1904.

562 THE PHYSIOLOGY OF REPRODUCTION

Franz,1 and others have confirmed Kehrer's observation, thus
proving that the movements are not dependent on impulses received
from the central nervous system. Those investigators showed that
the excised uterus may undergo regular contractions for a prolonged
period if placed in a warm bath of normal saline solution or on
having its vessels perfused with Locke's solution. According to
Franz the excised virgin uterus exhibits no spontaneous contractions,
but Helme and Kurdinowski state that they may occur, but that they
are much weaker than those taking place during and after pregnancy.
The movements of the uterus have lately been more fully
investigated by Cushny,2 who has carried out a large number of
experiments upon rabbits and other animals. This author states
that in virgins the unexcised uterus may remain motionless for a
long time, but that after manipulation or exposure to air rhythmic
contractions are often developed. He is disposed to believe, there-
fore, that the virgin uterus in the intact animal undergoes no
spontaneous movements. In animals in a state of " heat," and
during and after pregnancy, spontaneous contractions could generally
be discerned from the first, arid the author is doubtful if the organ
ever resumes its original inert condition after it has once been
pregnant. In some cases the movements seemed to occur almost
simultaneously throughout the entire organ, but in others the
circular muscle fibres contracted independently of the longitudinal,
and vice versa. Mechanical or electrical stimulation caused very
powerful contractions, but these were elicited more easily in the
pregnant than in the virgin uterus, while the increased irritability
was found to persist after pregnancy was over.

Helme stated that a shutting off of the blood-supply in the
excised and perfused uterus of the sheep brought about contraction.
Kurdinowski, on the other hand, found tfiat in the intact animal the
opposite effect was produced. Cushny's experiments for the most
part confirm those of Kurdinowski, but clamping the aorta in the cat
led to conflicting results, since in1 two cases it was succeeded by
relaxation and in three by contraction. Xo reason could be assigned
for this divergence.

It has long been known that uterine contractions can be induced
by nervous stimulation.3 Thus Serres 4 showed that irritation of the

1 Franz, "Studien zur Physiologie des Uterus," Zeitsch. f. Geburt. it,
vol. liii., 1904.

2 Cushny, "On the Movements of the Uterus," Jour, of Pkysiol., vol. xxxv.,
1906.

3 Feldman (The Principles of Ante-Natal awl Post-Natal Child Phti*i<>1n<i<i,
London, 1920) states that there are probably centres for uterine contraction
in the cortex, medulla, and cerebellum, since stimulation of these areas causes
uterine contractions, but he does not cite his authorities.

4 Serres, Anatomic Comparee du Cerveau, 1824.

INNERVATION OF THE GENERATIVE ORGANS 563

spinal cord in the .lumbar region excited the uterus to contract, and
later investigators have obtained similar results.1 Rohrig2 showed
that asphyxia which may bring about uterine contractions (and
abortion in the pregnant condition) cannot do so if the lumbar cord
is destroyed. Frankenhauser 3 and Korner4 discovered that the
efferent nerve fibres left the lumbar region of the spinal cord, and
after traversing the sympathetic, the inferior mesenteric ganglia and
the aortic plexus, made their way to the uterus. Langley5 found
that the majority passed to this organ by way of the sympathetic in
the region of the fourth, fifth, and sixth lumbar ganglia, so that
they probably arise from the third, fourth, and fifth spinal nerves.
Subsequently Langley and Anderson6 showed that stimulation of
the second, third, fourth, and fifth lumbar nerves (in cats and rabbits)
causes pallor and contraction of the Fallopian tubes, uterus, or
vagina, but that stimulation of the first and sixth lumbar nerves
produces no effect. They state that the efferent fibres are motor for
the muscular walls and vaso-constrictor for the small arteries. The
effect on the uterus and vagina was found to vary with the state of
the uterus in regard to parturition. Langley and Anderson state
that the sacral nerves send neither motor nor inhibitory fibres to any
of the internal generative organs, thus differing from Kehrer, Korner,
and others, who say that they obtained contraction of the uterus on
stimulating these nerves.

Keiffer7 also independently investigated the innervation of the
uterus, and the results obtained by exciting various nerves, his
observations agreeing for the most part with those of Langley and
Anderson.8

Cushny, in the paper already referred to, has described at some
length the effects of hypogastric stimulation, which produced in the
rabbit powerful contraction of the whole uterus irrespective of its
condition in regard to the occurrence of pregnancy. If the stimula-
tion was prolonged for more than fifteen seconds the organ remained
in a state of extreme contraction (tetanus uteri), but oscillations soon

1 Budge, " Ueber das Centrum genitospinale des Nervus sympatheticus,"
Virchoufs Archiv, vol. xv., 1858. Kiemaim, " Einige Bemerkungen iiber die
Innervation der Gebarmutter," Arch.f. Gyn&k., vol. ii., 1871.

2 Rohrig, " Experimentelle Untersuchungen iiber die Physiologic der
Uterusbewegung," Virchow's Archiv, vol. Ixxvi., 1879.

3 Frankenhauser, "Die Bewegungsnerven der Gebarmutteiy' Jeuaische
Zeitsch. f. Med., vol. i., 1864.

* Korner, Studien d. Phi/s. Instituts zu Brcslau, 1865.

6 Langley, loc. cit.

*' Langley and Anderson, loc. cit.

~ Keiffer, Recherches sur la Physiologic de P Uterus, Bruxelles, 1896.

8 Feldman (loc. cit.) states that motor nerve fibres to the uterus come from
the pneumogastric, phrenic, and splanchnic, and that sensory fibres pass through
the sacral nerves.

564 THE PHYSIOLOGY OF REPRODUCTION

began again and a gradual relaxation followed. Cushny shows also
that the hypogastric contains inhibitory fibres, and in one exceptional
case (a pregnant rabbit) stimulation of this nerve induced pure
inhibition, the uterus ceasing to contract at all. Moreover, in the
virgin cat the effect of hypogastric stimulation was inhibitory, the
organ undergoing relaxation. On the other hand, in the cat during
pregnancy, or as a general rule after pregnancy, hypogastric
stimulation led to strong and immediate contraction just as in the
rabbit. It is supposed, therefore, that the inhibitory fibres prevail in
the virgin, but that during and after pregnancy the action of the
motor fibres conceals their presence.1

Fellner - states that the " nervi erigentes " are motor for the
longitudinal muscles of the uterus and for the circular muscles of
the cervix, but are inhibitory for the circular muscles of the uterus
and the longitudinal muscles of the cervix. According to the same
author the hypogastric nerves are motor for the circular muscles of
the corpus uteri and for the longitudinal muscles of the cervix, but
are inhibitory for the longitudinal muscles of the uterus and for the
circular muscles of the cervix.

Dembo3 has described a peripheral nerve centre for the uterus in
the upper part of the anterior wall of the vagina in the rabbit.
Stimulation of this centre produced a very distinct contraction of
both uterine cornua.

According to Jacob4 there is an inhibitory centre for uterine
contraction situated in the medulla oblongata. This assertion is
based on experiments upon rabbits, in which it was found that

1 Cushny deals also with the action of various drugs on the uterus, and for
an account of this subject the reader is referred to his paper (loc. cit.). See also
Dale, " On some Physiological Actions of Ergot," Jour, of Physiol., vol. xxxiv.,
1906. The effects of temperature upon uterine contraction were first described
by Runge (M.) (" Die Wirkung hoher und niedriger Temperaturen auf den
Uterus," Arch. f. Gyntik., vol. xiii., 1878), who found that hot water caused
increased contraction followed by paralysis, while cold water produced tetanus.
Helme (loc. cit.) obtained results which were mostly similar. Kurdinowski
also found that cold excited contraction to tetanus, and that long-continued
mechanical stimulation produced exhaustion. Asphyxia did not cause con-
traction, and experimental anaemia had no effect.

2 Fellner, " Ueber die Bewegungen und Hemmungsnerven des Uterus,'*
Arch. f. Gynak,, vol. Ixxx., 1906. Labhardt ("Das Verhalten der Nerven in
der Substanz des Uterus," Arch. f. Gynak., vol. Ixxx., 1906) describes an
extensive system of nerves in the uterus of man and of the rabbit, the
main trunks lying between the middle layer of muscles and giving off intra-
fascicular bundles. Keiffer (Bull. Soc. d'Obstet., Paris, 1908, Nos. 2 and 3)
describes sympathetic ganglia in the uterine and vaginal walls in the course
of the large nerves coming from the hypogastric plexus.

3 Dembo, "Zur Frage iiber die Unabhangigkeit der Kontraktinen der
Gebarmutter von dem Cerebrospinalnervensystem," Abstract in Biol. Centralbl.,
vol. iv., 1885. (The original is in Russian.)

4 Jacob, " Ueber die Rhythmischen Bewegungen des Kaninchenuterus,"
Verhandl. der Phys. Gesell. zu Berlin, Arch, f. Anat. u. Phys., Phys. Abth.,
1884.

INNERVATION OF THE GENERATIVE ORGANS 565

stimulation of the medulla caused the movements of the uterus
to cease. Moreover, it is to some extent borne out by the fact that
the "pains" of labour can often be inhibited by emotions and other
contemporary actions of the central nervous system (see below, p. 572).

It is well known that uterine contraction can be induced by the
presence of a foreign body in the uterus, by injections into the
rectum, by the application of the child to the breast, and by various
other means. According to Kurdinowski1 the sensation of any
violent pain may cause uterine contraction in animals, and the organ
may respond to remote stimulation (e.g. in the ears). These observa-
tions alone are sufficient to show that the contraction is often a reflex
act. The experimental evidence cited above shows no less clearly
that the controlling centre is in the lumbar portion of the spinal
cord. Nevertheless there are many indications, as just mentioned,
that the movements of the uterus can be brought under the influence
of a higher centre situated in the brain. On the other hand, the
fact that rhythmical contractions can continue to occur in the absence
of all nervous connections is a certain proof that they are primarily
independent of the central nervous system, although normally they
are to a large extent influenced by it. It must be concluded,
therefore, that the power to contract and relax rhythmically is an
inherent property of the uterus.

The question as to the nature of the mechanism involved in
uterine contraction is inseparably connected with the further
problem concerning the part played by nervous influence in
controlling the course of parturition. This subject is dealt with
below (p. 570).

THE NORMAL COURSE OF PARTURITION IN THE HUMAN FEMALE

The increased size of the foetus, together with the accumulation of
the amniotjc fluid, causes the uterus towards the end of pregnancy to
become considerably distended. The enlargement is still further
increased by the growth of the uterine wall itself. Partly as a
consequence of this enlargement the waves of contraction which
were present at the beginning of pregnancy, or even previously, as
above described, become much more marked, but are still unaccom-
panied by painful sensation. With the onset of labour, however,
these unconscious painless contractions are replaced by others of
increasing intensity, and in the human subject distinctly affecting
consciousness and giving rise to severe suffering. These are the
" labour pains " which bring about the dilatation of the cervix uteri
and lead to the expulsion of the child followed by the placenta.

1 Kurdinowski, " Ueber die Reflectorische Wechselbeziehung zwischen den
Briistdriisen und dem Uterus," Arch. f. Gynak., vol. Ixxxi., 1907.

566 THE PHYSIOLOGY OF REPRODUCTION

At the commencement of labour the contractions do not occur
oftener than once every half or quarter of an hour, but they soon
become more frequent, and recur eventually at intervals of two or
three minutes. Their average duration is about a minute, though
actual pain is experienced for a shorter time.1 Polaillon2 and
Schutz 3 have shown from tracings that the period of increase occupies
the main portion of the " pain," its acme being of short duration. In
animals possessing bi-cornuate uteri the contractions are said to be
peristaltic in nature, but this is not so evident in the case of the
human subject.

Williams 4 has discussed the question as to the amount of force
exerted at each " pain " in a woman during delivery. He states that
the expenditure of energy necessary to restrain the head of the child
as it emerges from the vulva is represented by not more than fifty
pounds, although the obstetrician sometimes finds it impossible to
hold it back at the acme of the pain. Schutz 5 made an attempt to
arrive at a more exact estimation by inserting into the uterus a
rubber bag connected with a mercury manometer. He found that
whereas the intra-uterine pressure between the contractions was
represented by a column of mercury of 20 mm., during the pains it
rose to a height of from 80 to 250 mm. This difference is calculated
to represent a force of from 8-| to 27 £ pounds.

The clinical course of labour and the muscular forces concerned
in the process are fully dealt with in the text-books on Midwifery,6
and it is not proposed in the present work to devote more than a
very brief space to the consideration of this subject. It is customary
to divide the period of labour into three stages.

The first stage is characterised by the dilatation of the cervix
and os uteri. G-alabin gives the following account of the mechanical
processes which take place in the uterus during this stage of labour :
" There are three elements in the mechanism of dilatation of the
cervix and os ; first, the mechanical stretching by the bag" of mem-
branes; secondly, the contraction of the longitudinal fibres of the
uterus, which draw the cervix open ; and thirdly, the physiological
relaxation of the circular fibres, which [is always associated] with the
contraction of the body of the uterus. It follows from the principles

1 Williams (W.), Obstetrics, London, 1904.

'J Polaillon, Recherckes sur la Physiologic de V Uterus Gravide, Paris, 1880.

:{ Schutz, " Ueber die Formen der Wehenerven und ttber die Peristaltik des
Menschlichen Uterus," Arch. f. Gyniik., vol. xxvii., 1886.

4 Williams, loc. cit.

:> Schutz, " Ueber die Entwickelung der Kraft des Uterus in Verlaufe der
Geburt," Verkandl d. Deutsch. Gesell.fur Gynak., 1895.

6 See Williams, loc. cit. Galabin, Manual of Midwifery, 6th Edition,.
London, 1904, and the other text-books on the subject. See also Sellheim,
"Die Physiologic der Weiblichen Geschlechtsorgane," Nagel's Handbuch der
Physiologic des Menschen, vol. ii., Braunschweig, 1906.

INNERVATION OF THE GENERATIVE ORGANS 567

of mechanics that the effect of any given pressure within the bag of
membranes in producing a tension of the edge, either of the internal
or external os, is directly proportional to the diameter of the os, and
therefore vanishes when the os is very small. Hence, if the os is
closed to begin with, some dilatation by the stretching influence of
the longitudinal fibres must have taken place before the mechanism
of dilatation by the bag of membranes or parts of the foetus can come
into play. The mechanical action of the dilating part, as it is
pressed into the cervix, is that of a wedge; a fluid and uniform
wedge, in the case of the bag of membranes ; a solid and irregular
wedge, in the case of the head or other part of the foetus. It follows
that the effect produced by the wedge varies according to the
acuteness of its angle at the points where it is in contact with the
edge of the os. . . . It follows that the dilating force vanishes when
there is no projection, and becomes greater the more complete is the
projection. It follows also that it becomes progressively more and
more effective in proportion to the degree of dilatation which has
already been produced." l

The second stage, which has been called the expulsive stage, may
be said to include the period from the complete dilatation of the
os uteri to the delivery of the foetus. When the os has become fully
expanded, and the membranes have ruptured, there is generally a
short lull in the pains of labour. At the end of the lull the con-
tractions of the uterus begin to recur with increasing vigour and
frequency, while the abdominal muscles which are brought into play
for the first time exert on the uterus an additional extrinsic force
similar to that exerted on the rectum during defaecation. These
abdominal contractions are synchronous with those of the uterus, and
therefore, like them/tend to occur rhythmically. At the commence-
ment of the process the patient is able to some extent to control the
contractions by an effort of the will, but later on they, are quite
involuntary. The combined effect of the contractions is to drive
the child, usually head foremost, through the vagina and then out
through the vulva, these, however, playing a purely passive part in
the act of expulsion. Sometimes the membranes- do not rupture
before birth, and the child is born surrounded by a " caul."

The third stage of labour comprises the expulsion of the placenta.
After the delivery of the child the uterus ceases to contract for a
longer or shorter period, at the end of which its activity is renewed
once more. At this time the placenta becomes completely separated
from the wall of the uterus, and passes into the upper part of the
vagina. It is expelled thence through the action of the muscles of
the abdomen. During this stage there is almost invariably a certain

1 Galabin, loc. cit.

568 THE PHYSIOLOGY OF REPRODUCTION

amount of haemorrhage, which is represented in normal cases by from
three to four hundred cubic centimetres of blood.

The duration of labour shows considerable variation, but is
generally longer in primiparous women (i.e. those who have never
borne children before) than in multiparous ones. The average for
the former is rather more than eighteen hours, the three stages
respectively occupying sixteen, two, and from a quarter to half-an-
hour. The average for multiparous women is twelve hours, eleven
of which are occupied by the first, and one by the second stage.
The duration of labour in primiparous women depends also upon
age, being usually more prolonged in elderly subjects.

PARTURITION IN OTHER MAMMALIA

In animals the process of delivery varies somewhat in the different
animals. In the horse the fcetus, which has been lying on its back

FIG. 158. — The first stage in the revolution of the equine foetus. The os is
dilated by the membranes, which have not yet ruptured. (After Franck.
From Smith's Veterinary Physiology, Bailliere, Tindall & Cox.)

during intra--uterine life, preparatory to birth changes on to its side
and afterwards assumes the upright position, with its muzzle and
forelegs in the direction of the pelvis. Dilatation of the passage
follows, and the foal is delivered head first. In the cow and sheep
the movements which occur are essentially similar. It is stated that
the alteration in the position of the foatus is not brought about by
its own movements but by the uterine contractions. The revolution
of the foetus prior to -birth in the mare and cow is apparently
responsible for the torsion of the neck of the uterus which often
occurs in these animals.

Parturition in the mare is accompanied by a complete separation
of the chorion from the uterine wall. As a consequence of this fact

INNERVATION OF THE GENERATIVE ORGANS 569

any difficulty experienced in delivery usually causes the death of
the foal. In Ruminants, on the other hand, the separation of the
cotyledons takes place very gradually, so that the connection between
the maternal and foatal circulation is maintained to some extent
until the last. In these animals the process of parturition may last
for hours (in the cow, about two hours ; in the sheep, about fifteen
minutes for each lamb born). In the mare, on the contrary,
delivery is usually effected very rapidly1 (five to fifteen minutes).
In the sow, bitch, and cat it takes from ten to thirty minutes for
each young one born, with sometimes an interval of an hour between
the births. The foetal membranes may be expelled with the young

FIG. 159. — The foal in the normal position for delivery, the revolution being
completed and the membranes ruptured. (After Franck. From Smith's
Veterinary Physiology, Bailliere, Tindall & Cox.)

or be retained until a little later, when the uterus recovers its power
and then expels them (in the mare several hours after the foal
is born).

In the Garni vora the mother usually gnaws through the umbilical
cord but in the other animals it is torn.

In animals such as the rat, in which multiple .conception is the
rule, the " presentation " of the young at birth may be either " breech "
or " head." The foetuses tend to be expelled irregularly,, some being

1 Smith (F.), Veterinary Physiology, 3rd Edition, London, 1907. Fleming,
Veterinary Obstetrics, Craig's Edition, London, 1912. Wortley Axe, "The Mare
and Foal," Jour. Royal Agric. Soc., 3rd Series, vol. ix., 1898. Leeney, " The
Lambing Pen," Jour. Royal Agric. Soc., 3rd Series, vol. vii., 1896. Article on
" Parturition " by the same author in The Standard Cyclopedia of Modern
Agriculture, vol. ix., London, 1910.

570 THE PHYSIOLOGY OF REPRODUCTION

discharged along with the placenta, while others are born
separately.1

Hartmann2 has described the phenomena attending parturition
in the opossum (Didelphys virginiana). The very immature young
make their way unaided to the mother's pouch, and in so doing
crawl three inches from the vagina over an entanglement of hair ;
amid a forest of hair the "ten-day-old foetus" finds the nipple.
Hartmann mentions that he found thirteen teats with eleven young
attached.

In the actual process of being born the foetuses of the opossum
do not pass out through the lateral canals of the vagina, but break
through a cleft-like rupture, the "pseudo-vaginal canal," into the
median canal. This occurs also in Dasyurus and Perameles.3

The young kangaroo, like the opossum, reaches the pouch
unaided.

THE NERVOUS MECHANISM OF PARTURITION

Parturition may be considered as being normally a reflex act, the
centre of which is situated in the lumbar region of the spinal ' cord.
On the other hand, it has been shown from experiments upon animals .
that the transmission of impulses through the cord is not absolutely
essential to the occurrence of parturition.

Simpson (Sir James)4 removed the spinal cord from the first
dorsal vertebra downwards from a number of sows a few days before
parturition was due. Some* of the animals died as a result of the
operation, but in others parturition proceeded normally, excepting
that in each case the last foetus of the series was not born. " The
uterine contractions proceeding from fundus to cervix were sufficient
to expel the foetuses from the uterus ; and each foetus as it came into
the vagina was thence extruded by the force transmitted from the
foetus behind it; but when the last foetus came into the vagina it
remained there, because there was nothing to transmit the uterine
expulsive force, while the vaginal and abdominal muscles, being under
the influence of the spinal nerves, had been rendered powerless by
the removal of the spinal cord."

1 Brumpt, " Parturition chez le Rat blanc," Bull. Soc. Zool. France, vol.
xxxii., 1907. The loosening of the placenta and other changes in Tupaia are
described by van Herwerden, " Die puerperalen Vorgange in der Mucosa uteri
von Tupaia javanica" Anat. Hefte, vol. xxxii., 1907.

2 Hartmann, "Studies in the Development of the Opossum, and the
Phenomena of Parturition," Anat. Record, vol. xix., 1920.

3 Hill, " On the Fretal Membranes, Placentation, and Parturition of the Native
Cat," Anat. Anz., vol. xviii., 1900. See also Proc. Linn. Soc. of N.S. Wales,
vols. xxiv. and xxv., 1899 and 1900. The lateral vaginal canals are described
as enlarging in the prooestrum, containing a lymph-like fluid during oastrus
when they are enormous and act as seminal reservoirs, since several days
elapse between copulation and ovulation and subsequently becoming reduced.

4 Simpson, Selected Obstetric Works, edited by W. H. Black, Edinburgh, 1871.

Riemann l states that after the destruction of the cord of a cat
from the third dorsal vertebra downwards the animal gave birth to
a kitten two days subsequently, shortly before its death.

Rein 2 describes experiments upon rabbits in which he severed the
uterus from all nervous connection with the cerebrospinal system, and
found afterwards that the mechanism of labour was not destroyed.

Furthermore, Oser and Schlesinger,3 as a result of experimental
evidence, state that parturition can occur in animals after the
severance of the sympathetic nerves which pass to the uterus, but it
is difficult to understand how this operation could have been made
complete without interfering with the blood-supply to that organ.

More recently, Goltz and Ewald 4 have described an experiment
in which they completely exsected the spinal cord of a bitch from the
mid-dorsal region downwards, and found that after the operation
the animal experienced normal " heat," became pregnant, and in due
course produced a litter of pups. Kruiger and Offergeld 5 have also
shown that parturition is possible after destruction of the cord. Goltz
had already shown 6 that parturition could occur after the transection
of the spinal cord in the dorsal region, and consequently after all
connection with the higher centres had been cut off (see p. 514).

The last-mentioned fact is also demonstrated in the various cases
in which parturition has proceeded normally in women suffering from
paraplegia from the level of the mid-dorsal part of the spinal cord
downwards. Routh 7 has recorded several such cases, and in all of
them labour set in and proceeded regularly (or almost regularly), but
without sensation. In Routh's own patient the injury was in the
dorsal region of the cord, which was completely disorganised at the
seat of the fracture of the spine, as the post-mortem evidence showed.
In the lumbo-sacral region, however, there were a large number of
cells which were normal in appearance, so that it could not be
contended that the centre for parturition had been destroyed. Routh
also refers to Brachet's case,8 which he states is the only one recorded

1 Riemann, " Einige Bemerkungen iiber die Innervation der Gebarmutter,"
Arch. f. Gynak., vol. ii., 1871.

2 Rein, " Beitrag zur Lehre von der Innervation des Uterus," Pfliige^s
Archiv, vol. xxiii.

3 Oser and Schlesinger, " Experimentelle Untersuchungen iiber Uterus-
be wegungen," Strieker's Ned. Jahrbiicher, 1872.

4 Goltz and Ewald, "Der Hund mit verkurzteni Ruckenmark," P/luger>s
Archiv, vol. Ixiii., 1896.

6 Kruiger and Offergeld, "Der Vorgang von Zeugung, Schwangerschaft,
Geburt, und Wochenbett an der ausgeschalteten Gebarmutter," Arch. f. Gynak.,
vol. Ixxxiii., 1908.

6 Goltz, " Ueber den Einfluss des Nervensystems auf die Vorgange wahrend
der Schwangerschaft und des Gebarakts," Pfluger's Archiv, vol. ix., 1874.

7 Routh, "Parturition during Paraplegia," Trans. Obstet. Soc. Land., vol.
xxxix., 1898.

8 Brachet, Recherches, 2nd Edition, Paris, 1837.

572 THE PHYSIOLOGY OF REPRODUCTION

in which the spinal lesion was apparently in the lumbar region of the
cord. In this case the uterus failed to make the normal contractions,
and the child was eventually extracted with forceps. The placenta
also had to be removed by hand. It is clear, therefore, that a spinal
lesion in the lumbar region may result in materially weakening the
action of the uterus, and so may hinder the normal course of labour.
On the other hand, in those cases in which the lesion was in the
dorsal part of the cord, the possibility of spinal reflexes in the lumbar
region could not be excluded.1

The following general conclusions regarding the nervous mechanism
of parturition are based largely on those of Kouth. (1) The act of
parturition is partly automatic and partly reflex, these actions
corresponding in the main to the first and second stages of labour
respectively, the spinal reflexes usually commencing as soon as the
membranes have ruptured. (2) Direct communication with the brain
is not essential for the proper co-ordination of uterine action, but
the brain appears to exercise a controlling influence of some kind.
Thus, emotions often become a hindrance to the progress of parturition.
It would seem possible that this inhibition of uterine contractions is
brought about by an inhibition of a centre in the brain (see above,
p. 564). (3) Direct communication between the uterus and the
lumbar region of the cord is generally essential for the occurrence of
those rhythmical contractions which take place during the progress
of normal labour. There is experimental evidence upon animals,
however, that the uterus is sometimes able automatically to expel its
contents, at least as far as the relaxed portion of the genital cord,
even when entirely deprived of all spinal influence.2

CHANGES IN THE MATERNAL ORGANISM

The influence of parturition upon the metabolism of the maternal
organism is dealt with by Sellheiin.3 There is a slight rise of
temperature during the process, and the pulse rate is also affected,
being much quicker during the pains, but slower between them, the
difference amounting to as much as thirty-six beats a minute. The
blood shows a marked leucocytosis, and the blood pressure is higher.
Urine is secreted in smaller quantities, and is liable to contain traces,
of renal epithelium, red and white blood corpuscles, and albumen.

1 Routh also discusses post-mortem parturition, but points out that in most
of those cases where it occurred, the expulsion of the foetus was caused by
increased abdominal pressure due to putrefactive gaseous distension during a
condition of muscular relaxation. There are some facts which go to prove that
uterine contractility and retraction may continue or even commence after death,
possibly resulting from the movements of the imprisoned child.

2 For further references to the literature of the nervous mechanism of
parturition, see Bechterew, Die Fuiiktionen der Nervencentra, Weinberg's
German translation, vol. i., Jena, 1908.

:! Sellheim, loc. cit.

INNERVATION OF THE GENERATIVE ORGANS 573

THE CAUSE OF BIRTH

Foster in his " Text-Book of Physiology " l has written as follows :
" We may be said to be in the dark as to why the uterus, after
remaining for months subject only to futile contractions, is suddenly
thrown into powerful and efficient action, and within it may be a few-
hours, or even less, gets rid of the burden which it has borne with
such tolerance for so long a time. None of the various hypotheses
which have been put forward can be considered as satisfactory. We
can only say that labour is the culminating point of a series of
events, and must come sooner or later, though its immediate advent
may sometimes be decided by accident." What Foster wrote about
this problem is 'now only partly true, but although progress has been
made towards its solution no complete answer has yet been given to
the question as to the immediate cause of parturition.

Williams2 has classified the various theories which have been
formulated under eleven heads. These may now be briefly considered
in the ouder adopted by him.

(1) The increasing irritability of the uterus, as manifested by
its greater tendency to respond to stimulation in the later stages of
gestation, is probably a factor in determining the time of birth. As
already described, the uterine contractions towards the close of
pregnancy are not only more frequent, but they are also much more
intense. This growing irritability is no doubt to be associated in
part with the increase in the size of the foetus.

(2) It is suggested that the mere distension of the uterus must,
after a certain point, lead to a reaction, when the organ attempts to
reduce itself to its former size, and so expels its contents. This
idea receives some support from the fact that twin pregnancies and
hydramnios (or the presence of an excessive quantity of liquor anmii)
often result in premature labour.

(3) It has been supposed from early times onwards that parturi-
tion might be brought about through the pressure of the foetus
producing a gradual dilatation of the cervix. Williams, however,
has pointed out that this condition of the cervix cannot be the
sole factor, since in a certain number of cases, especially in twin
pregnancies, a pronounced dilatation has been known to occur for a
considerable period prior to the onset of labour.

(4) Keilmann,3 working upon the bat, came to the conclusion that
the onset of labour was caused by the increasing pressure set up
by the lower distended portion of the pregnant uterus (the lower

1 Foster, Text-Book of Physiology, oth Edition, vol. iv., London, 1891.

2 Williams, loc. cit.

3 Keilmann, "Zur Klarung der Cervixfrage," Zeitsch. f. Geb. u. Gyniik.,
vol. xxii., 189?.

574 THE PHYSIOLOGY OF REPRODUCTION

uterine segment) upon the surrounding nerve ganglia. Supposing
this conclusion to be correct as applied to the bat, it is not quite
clear that it is equally applicable to the human female and to other
animals.

(5) Simpson l and others were of opinion that the " pains " of
labour were the indirect result of a partial separation of foetus and
decidua, brought about by the fatty degeneration of the latter in
the last stages of pregnancy, so that the fostus became virtually
converted into a foreign body, which caused the uterus to respond
accordingly. It is true that part of the maternal placenta undergoes
degenerative changes towards the end of pregnancy, but there is no
evidence that this by itself is sufficient to cause a separation of the
foetus from the uterine wall.

(6) There is no evidence in support of the theory that the
exciting cause of parturition is an accumulation of carbon dioxide
in the blood, beyond the fact demonstrated by Brown-Sequard,2
Keiffer,3 and others, that uterine contractions can be induced
experimentally by this means.

(7) Spiegelberg4 put forward the theory that parturition was
brought about through the action of substances secreted by the
foetus and passed into the maternal blood. These hypothetical
substances, which appear to have been comparable to Starling's
hormones, were supposed to act on the uterine centre in the spinal
cord. Spiegelberg suggested, further, that the exciting substances
were elaborated as a result of an insufficiency of nutrition, and were
an indication that the mature foetus required other sustenance than
that supplied to it through the placenta. This theory appears to be
devoid of all experimental basis, but it is not opposed by any of the
known facts.5

(8) Tyler Smith,6 Minot,7 Beard,8 and others have held the view
that there is a connection between parturition and menstruation, the
two processes being physiologically homologous. According to this
theory, there is an increased tendency towards uterine contractions

1 Simpson, loc. cit.

2 Brown-Sequard, Experimental Researches, English translation, London,
1853.

3 Keiffer, loc. cit.

4 Spiegelberg, " Die Dauer der Geburt," Lehrbuch der Geburtshiilfe, vol. ii.,
1891.

5 Van der Heide states that he induced labour pains at full term in
pregnant women by injecting foetal blood-serum. According to the same
author the maternal blood of rats in late pregnancy contains substances toxic
to non-pregnant animals (Jour. Med. Research, vol. xxix., 1914).

6 Tyler Smith, Parturition and the Principles and Practice of Obstetrics,
London, 1849.

7 Minot, " Uterus and Embryo," Jour, of Morph., vol. ii., 1889. " Human
Embryology."

8 Beard, The Span of Gestation and the Cause of Birth, Jena, 1897.

INNERVATION OF THE GENERATIVE ORGANS 575

at the periods at which menstruation would occur if the condition
were nob one of pregnancy. Thus Tyler Smith says that there is in
all women a greater tendency to abort at the times represented by
the catamenial periods. According to Minot, the menstrual and
gravitidal changes follow the same cycle of events, the pregnant
uterus passing through a prolonged and intensified " menstrual cycle."
Consequently, it is probable that there is a common cause for the
ending of the series (the casting off of the superficial part of the
mucosa in both cases'). This theory has been further elaborated by
Beard, who has arrived at the conclusion that parturition takes place
at the time it does in order that a new ovulation may be carried into
effect. This author lays great stress upon the rhythmical character
of the sexual processes, and points out in support of his theory that
" heat " and ovulation frequently ensue shortly after parturition.
That this does not happen in many animals has been already shown
in the second chapter of this work.1 Moreover, Beard's theory makes
no attempt to explain why parturition should occur in some animals
at the close of one particular ovulation interval (e.g. in the human
species at the close of the tenth), and in other animals at the
termination of a different one (that is to say, no explanation is given
of the variation in the number of ovulation intervals which are
comprised in the period of gestation in different animals). It cannot
be said, therefore, that Beard's hypothesis as to the time occupied by
gestation and the cause of birth is an adequate one.

(9) Various writers, such, as Geyl,2 have laid some stress upon the
belief that parturition occurs in women at a time which has proved,
after long ages, to be the most suitable for the perpetuation of the
race. A similar statement might of course be made about any other
existing species of mammal, for it is only another way of stating
the generally accepted belief that parturition, like all other natural
phenonema in the animal world, is under the control of natural
selection. In support of this contention, as applied to the human
species, it has been pointed out that when labour takes place after
an abnormally prolonged gestation, it frequently results in dead
children, while, on the other hand, premature labour results in puny,
ill-developed children, who often perish in early life.

(10) Eden,3 and also Williams, have pointed out " that the
frequent occurrence of infarct formation [i.e. a certain kind of.

1 Beard holds that ovulation takes place shortly after parturition in all
Mammals. This is not the case in any monoestrous animals which have a
prolonged anrestrous period.

2 Geyl, " Ueber die Ursache des .-Geburtseintrittes," Arch. f. GynaL,
vol. xvii., 1881.

3 Eden, " A Study of the Human Placenta," Jour, of Path, and Bacteriol.,
vol. iv., 1897.

576 THE PHYSIOLOGY OF REPRODUCTION

degenerative change] in the placenta at term must be regarded as
evidence of its senility, and that this change is analogous to the
obliteration and atrophy of the chorion hieve at an earlier period.
Where these changes are marked the nutrition of the foetus must
be interfered with, and it is possible that certain of its metabolic
products may result in stimulation of the uterine centre."1 This
theory should be compared with that advanced by Spiegelberg (see
above).

(11) Lastly, Williams calls attention to the fact that excessive
physical fatigue, sudden jars or violence, mental emotion, fright, etc.,
may lead to the termination of gestation in women. Similarly, it is
well known that circumstances of a like nature may induce abortion
in animals.

Williams remarks that in all probability the onset of labour in
most cases is due to a combination of a number of the above-
mentioned causes. The main objection to all the theories which
have so far been advanced is that they take no account of the
complexity of the problem. An hypothesis may be fairly adequate
as a general explanation of the duration of gestation, while at the
same time taking no account of the immediate cause of birth. Thus,
it is no doubt true that the time of parturition is determined largely
by the necessities of the offspring, but this conclusion provides no sort
of explanation as to why it is that the process in any one particular
species generally commences at a certain fixed stage of development,
and it remains for us to assume that it is one of the inherent
properties of the uterus and correlated organs in the species in
question that it should do so. Even on this assumption it is
impossible to avoid concluding that there must be some definite
exciting cause.

Some light is thrown on this question by the study of the
condition of pseudo-pregnancy (see pp. 33 and 36). The three
animals in which it is known are the dog, the marsupial cat, and
the rabbit (the latter only under experimental conditions). In each
of these species during pseudo-pregnancy there is a persistent corpus
luteum which at or near the end of the period enters into a state of
involution and so probably is in a condition which is not dissimilar
to that of the corpus luteum verum; at the end of gestation. Further-
more all these animals at the termination of pseudo-pregnancy2 display
habits or instincts which are iisually associated with the act of
giving birth. Thus the. bitch may prepare a bed as if for a litter
of pups, the female Dasyurus cleans out her pouch as if for the
reception of young, and the doe ^rabbit plucks her breast of fur and
uses it to line a nest. Since these habits are displayed at the end

1 Williams, loc. cit. - In the rabbit about the eighteenth day.

INNERVATION OF THE GENERATIVE ORGANS 577

of pseudo-pregnancy, which, as we have seen, is dependent on the
persistence of the corpus luteum, it is reasonable to suppose that the
processes associated with actual parturition after true pregnancy are
correlated similarly with changes in the ovarian internal secretions.
Ancel and Bourn l have supposed that in the first part of pregnancy
the tolerance of the uterus for the foetus is due to the corpus luteum,
and in the second half that it is caused by the myometrial gland
(see p. 618), but Hammond2 has shown that it is much more likely
that the corpus luteum is the responsible organ throughout the whole
of gestation. Further, Sharpey Schafer3 has shown that the ovaries
produce two hormones (see p. 621), one inhibiting the contractility
of plain muscle and the other increasing it. Similarly, Guggisberg,4
by injecting extract of corpus luteum into the extirpated uterus, in
some cases obtained increased contraction, in others relaxation. It
seems probable that whereas during pregnancy the inhibitory
secretion is produced in greatest abundance, at the end of pregnancy
the secretion which has an excitatory effect on uterine or other
muscle may be dominant in its influence, and so promote the act
of giving birth and the processes which are associated with it.

The causes of abortion or premature parturition are disciissed
below in the chapter on fertility.

PROLONGED GESTATION

The duration of gestation in any one species usually varies within
quite narrow limits, but under exceptional circumstances it may

1 Ancel and Bouin, " Sur le Determinisme de PAccouckement," (J. R. de
I'Acad. des Sciences, vol. cliv., 1912.

- Hammond, " On the Causes Responsible for the Developmental Progress
of the Mammary Glands, etc.," Proc. Ray. Soc., B., vol. Ixxxix., 1917.

3 Sharpey Schafer, The Endocrine Organs, London, 1917. Itagaki states
thatf extract of corpus luteum generally produces an increase of tone in the
uterus, but sometimes the opposite effect is brought about. This difference is
not due to condition of pregnancy or non-pregnancy, nor to the strength of
the extract, but to differences in the samples of corpus luteum. Extract may
produce relaxation in other muscular tissues. Liquor folliculi caused increase
in tone of uterine and other muscles. Extract of hilum ovarii (containing
interstitial cells) caused inhibition of uterine muscle, but increase of tone in
intestine. ("The Influence of Corpus Luteum Extracts upon Plain Muscle,"
and "On the Action of Various Extracts, etc.," i^uar. Jour. Exp. Pht/sioL,
vol. xi., 1917.) See also Athias, who describes the effects of various extracts
of internally secretory organs upon uterine movements, especially after
ovariotomy. (" Effets de la Castration sur les Mouvements Automatiques de
1'Uterus chez le Cobaye," Jour, de Phys. et de Path. Gen., vol. xviii., 1919 ;
Arch. Intemat. de Pharm. et de Ther., vol. xxv., 1920.) The rhythmical
contractions after ovariotomy become enfeebled and eventually die away, but
the " tonic " oscillations persist.

4 Guggisberg, "Ueber die Wirkung der inneren Sekrete auf die Tatigkeit
des Uterus," Zeitsch. f. Gel. und Gyn., vol. Ixxv., 1913. Extracts of pregnant
uterus or of placenta caused contraction.

19

578 THE PHYSIOLOGY OF REPRODUCTION

continue for an abnormally long period. Thus, Williams l records
a case of a woman with whom pregnancy extended for over eleven
lunar months after the cessation of menstruation, instead of the
usual ten lunar months (i.e. about 280 days). In this case typical
labour pains were experienced at the end of the tenth month, but
these subsided after a short tune, and were not renewed until four
weeks later, when they resulted in parturition. The same woman
became pregnant a second time, when the period of pregnancy was
again prolonged until the end of the eleventh month after the last
menstruation. The children on each occasion were abnormally large
and* heavy at birth. Allen2 has recently recorded a number of
further cases of prolonged gestation in women, the longest time
chronicled being 334 days. It is stated that inertia of the uterus
(due to fatty degeneration) is frequently associated with prolonged
gestation ; but the occurrence of the latter is no doubt often brought
about by other causes which are at present unknown.

Cases of prolonged gestation have been observed also among
animals. Professor Ewart has informed the writer of a mare in his
possession in which the period of gestation was extended to twelve
months instead of the usual eleven. Other cases of prolonged
gestation in mares, and also in cows, have been recorded by Tessier 3
and Franck-Albrecht-Goring,4 and appear to be not uncommon.
No satisfactory reason has been suggested to account for such cases.

According to Pinard 5 prolonged gestation may occur in Rodents
(Dipodillus simoni, Meriones shaivi, M. longifrons, Mus musculus, etc.),
as a result of suckling a large litter produced just previously to a
second gestation, as if the development of the young during the
latter were arrested by a relative insufficiency of nourishment. In
some cases the period of gestation was half as long again as the
normal duration.

Kirkham 6 says that with white mice where more than two young

1 Williams, foe. cit.

2 Allen (L. M.), "Prolonged Gestation," Amer. Jour, of Obstet., vol. lv., 1907.

3 Tessier, " Recherches sur la Duree de la Gestation, etc.," Mem. de VAcad. des
Sciences, Paris, 1817.

4 Franck-Albrecht-Goring, "Die Trachtigkeitsdauer," Thierarztliche Gelmrt-
shUlfe, vol. iv., 1901.

5 Pinard, Article "Gestation," Richet's Dictionnaire de Physiologic, vol. vii.,
Paris, 1905.

6 Kirkham, "The Prolonged Gestation Period in Suckling Mice," Anat. /.'«.,
vol. xi., 1916 ; "The Life of the White Mouse," Proc. Soc. Exp. Biol. and M<>rl,
vol. xvii , 1920. Kirkham and also Adler, writing earlier, state that the
mammary glands exert an inhibitory influence upon the stimuli coming from
the blastula or from the corpus luteum. (Adler, " Versuche mit ' Mammimum
Poehl' betreff'end die Funktion der Briistdriise als innerlich sezernierendes
Organ," Munch. Med. Woch., vol. lix., 1912.) That the gestation period in
suckling mice is lengthened had been previously noted by Daniel (" Gestation
in White Mice," Jour. Exp. ZooL, vol. ix., 1910), while Miss King records
similar phenomena in white rats (liioL /lull., vol. xxiv., 1913).

INNERVATION OF THE GENERATIVE ORGANS 579

are being suckled and the mother becomes pregnant the implantation
of the embryos is retarded for about nine clays, and until suckling-
ceases, and that a corresponding prolongation of the period of
gestation occurs, as compared with that of non-suckling females.
In other cases of suckling mice, according to Kirkham, ovulation
is inhibited or postponed. These phenomena are interpreted as
being of a protective nature to the parent organism, since mice whose
litters are removed at birth usually produce young so frequently
that they die of exhaustion before reaching their climacteric.

THE PUERPERIUM

In multiparous women the uterus continues to contract and relax
at more or less regular intervals after the expulsion of the placenta
which marks the termination of the third stage of labour. The
contractions which occur at this period give rise to the sensations
commonly known as the " after-pains." These may last several days,
but are not generally very severe after the first day. They are
particularly liable to occur when the child is put to the breast, a
fact which seems to indicate a nervous connection between the
uterus and the mammary glands. In primiparous women the tonicity
of the puerperal uterus is usually greater than in multiparous ones,
so that the uterus is capable of remaining during this period in a
state of almost uninterrupted retraction unless blood clots or other
foreign bodies are present in the cavity, in which case the organ
undergoes movements in attempting to expel them.

This tonic retraction of the uterus is an important factor in
closing the blood sinuses, and so preventing bleeding. If, owing to
any circumstance, the normal contraction and retraction of the
uterus are interfered with, post-partum haemorrhage is liable to
occur. This is not infrequently the case with white women who
have migrated to the tropics, or with ill-nourished women in the
slums, in whom, owing apparently to an inefficiency in the uterine
nerve supply, the organ tends to become inert.1 It follows from
what has been said that multiparous women are more liable to
post-partum haemorrhage than primiparous ones.2

According to Longridge the anaemic condition of the normal
puerperal uterus is due partly to the effacement of the ovarian and
uterine arteries which occurs when the uterus contracts. "The

1 Longridge, The Puerperium, London, 1906.

2 Longridge has pointed out, however, that the amount of post-partum
discharge in multipart is not as a rule in proportion to the severity of the
"'after-pains," and consequently that the latter cannot be ascribed simply to
defective retraction on the part of the uterus. He suggests, therefore, that
the "after-pains" in multipart are largely due to the uterus suffering from
cramp resulting from the excessive exertion involved in discharging the child.

58o THE PHYSIOLOGY OF REPRODUCTION

reality of this occurrence is supported by an observation which can
be made in many cases of Cnesarian section ; in this operation it is
noticed that as long as the uterus remains outside the abdomen it
tends to bleed, but that as soon as it is dropped back bleeding
ceases. It is not the warmth of the abdominal cavity that checks
the bleeding, since it may continue when the uterus is wrapped in
warm towels outside the abdomen. But the mere fact of pulling up
the uterus opens out the concertina, as it were, and allows blood to
now through the arteries. If the bladder is full at the end of labour,
the uterus is pushed upwards, and slight loss may continue until the
water is drawn off. As soon as the uterus is allowed to nestle down
into its normal position the bleeding stops." l

The puerperal vaginal discharge is known technically as the
lochia. It varies considerably in amount in different individuals, and
changes in character as the puerperium proceeds, ceasing altogether
about the middle of the third week. For the first few days it
consists almost entirely of blood, which makes its way from the raw
surface of the uterus and from lacerations caused during delivery.
This is the lochia rubra. After three or four days it becomes paler,
owing to the dilution of the sanguineous discharge by mucous
secretion. This is called the lochia serosa. During the next three
days the normal colour of the lochia is brown. This change (from
pale pink to brown) is due to the fact that the normal acidity of the
vaginal secretion has by this time become re-established. Longridge
suggests that the brown colour is probably the result of the formation
of some such compound as acid heematin. After about the tenth day
the lochia assumes a whitish or yellowish-white colour, owing to the
admixture of leucocytes and the cessation of the blood flow. It is
then known as the lochia alba. In many cases, however, traces of
blood may be observed for weeks, but the lochia alba consists mainly
of secretions from the vagina and cervix, together with leucocytes, a
few epithelial cells, fragments of decidual tissue, and crystals of
cholesterin. Micro-organisms are also present in the discharge, but
recent investigations have shown that the lochia obtained directly
from the uterine cavity does not contain bacteria, excepting in cases
where the uterus is the seat of infectious processes.2

The average quantity of the discharge has been computed by
Gassner3 at 1485 cubic centimetres, or about 50 ounces. Giles4

1 Brock (Practitioner, January 1908) has recently expressed the opinion
that puerperal bleeding is chiefly venous, pointing out that the discharge is
usually very dark in colour.

2 Kronig, Bakteriologie des Genitalkanales, etc., Leipzig, 1907.

3 Gassner, "Ueber die Veranderungen des Korpergewichtes bei Schwangeren,
Gebarenden, und Wochnerinnen," Monatsschr. f. Geburtskunde, vol. xv., 1862.

4 Giles, "On the Lochia," Trans. Obstet. Soc., vol. xxxv., 1897.

INNERVATION OF THE GENERATIVE ORGANS 581

estimated it as 10 1 ounces (or considerably less than Gassner's
estimation), and found further that in women who were accustomed
to bleed freely at the menstrual periods the amount of the lochial
discharge was beyond the average. According to Gassner, the
discharge is generally less in women who suckle.

The uterus after delivery becomes rapidly reduced in size. This
process is known as the involution of the uterus; it is completely
effected in from five to eight weeks, the greatest reduction taking
place in the first few days. Thus the freshly delivered uterus weighs
on an average 1000 grammes (or about two pounds), a week later it
weighs only half that amount, at the close of the second week 375
grammes, and at the end of the puerperal period as little as
60 grammes (or about two ounces). Its decrease in size is such that
by the tenth day after parturition the organ is once more confined
to the cavity of the pelvis proper, and cannot be felt above the
symphysis.

The process of uterine involution is the result chiefly of changes
occurring in the muscle walls.1 The size of the individual cells
becomes very markedly diminished, but there is little or no reduction
in their number. Fatty degeneration does not take place in the
muscular tissue. It is stated that the retraction of the muscle fibres
produces a compression of the vessels, and that the comparatively
anaemic condition of the puerperal uterus, especially in the earlier
stages, is due to this cause. Subsequently the uterus becomes more
vascular again.

The remains of the decidua which are not expelled at parturition
undergo degeneration and are discharged in the lochia, leaving only
the fundi of the glands and a certain amount of connective tissue
from which the uterine stroma is renewed. The epithelium is
re-formed from that of the glands, as shown by Friedlander,2 Kundrat
and Engelmann,3 Leopold,4 Kronig,5 and others.6 Excepting in the
position of the placenta, the new epithelium is completely regenerated
by the end of the sixth week after delivery.

1 The account given of the changes in the uterus during the puerperium is
based largely on that given by Williams (Obstetrics, New York, 1904). See
also Sellheim, " Das Wochenbett," in Nagel's Handbuch der Physiologic des
Menschen, vol. ii., Braunschweig, 1906, where further references are given.

- Friedlander, Physiologische und Ariatomische Untersuchungen iiber den
Utems, Leipzig, 1870.

3 Kundrat and Engelmann, " Untersuchungen iiber die Uterusschleimhaut,"
Strieker 's Ned. Jahrbuch, 1873.

4 Leopold, tftudien iiber die Utenwschleimhaut, etc., Berlin, 1878.

5 Kronig, "Beitrag zum anatomischen Verhalten der Schleimhaut der Cervix
und des Uterus, etc.," Arch. f. Gynak., vol. Ixiii., 1901.

0 Leusden, assuming the syncytial tissue of the deciduum to be of maternal
origin, has suggested that it may assist in giving rise to the new epithelium
(" Ueber die Serotinalen Riesenzellen, etc.," Zeitsch.f. Geb. und Gynak., vol. xxxvi.,
1897).

582 THE PHYSIOLOGY OF REPRODUCTION

The placental area at the end of parturition is marked by the
presence of thrombosed vessels. It is raised above the general
surface of the uterine wall, and is irregular in shape. It very soon
diminishes in size, its diameter being not more than two centimetres
long at the end of the puerperal period, although its former position
may be detected as an area slightly stained by blood pigment for
several months after delivery.

Williams states that in the last month of pregnancy some of the
sinuses at the placental area undergo thrombosis, but that this
process becomes much more marked after the completion of labour,
although many of the sinuses are simply compressed by the contract-
ing uterine muscles without ever becoming thrombosed.1 The
thrombi are eventually converted into ordinary connective tissue
by a cellular proliferation from the lining membrane of the vessel.s
While this change is in progress the lining membrane presents a
folded appearance somewhat resembling a typical developing corpus
luteum. This is especially well seen about the fourth week after
parturition, but even up to the end of a year the convoluted appear-
ance is still sometimes discernible.2 The lumina of the arteries become
reduced in size, but the thickening of their walls, which takes place
during pregnancy, is an alteration of a more permanent character.
This histological change affords a means of discriminating between
a virgin and a parous uterus.

Leo Loeb and Huramitau3 have studied the involution of the
uterus in the guinea-pig and find that it is favoured by suckling.
They regard the effect on the uterine tissues as acting directly, and
not indirectly by way of the ovaries. Castration is 'stated to favour
uterine involution in the guinea-pig.

The human cervix remains for some time after delivery as a soft
flaccid structure with lacerated edges, but it gradually undergoes
involution, the lumen becoming narrower. The vagina takes about
the same time to recover as the uterus. After a first delivery its
outlet remains permanently wider than before. The rug?e reappear
about the third week. The place of the hymen is taken by numerous
small tags of tissue which become transformed into the carunculse
myrtiformes. The condition of the labia majora and labia minora is
generally flabby and atrophic as contrasted with that existing in
virgin women.

1 According to Longridge (see below in the text), thrombosis is of little or
no importance in assisting the haemostasia of normal labour.

2 Williams (Sir J.), " Changes in the Uterus, etc.," Trans. Obstet. Soc., vol. xx.,
1878. See also Helme, "Histological Observations, etc.," Trans. Roy. Soc. Edin.,
vol. xxxv., 1890.

3 Huramitau and Leo Loeb, "The Involution of the Uterus following
Labour," Ainer. Jour. Physiol., vol. lv., 1921.

INNERVATION OF THE GENERATIVE ORGANS 583

The characteristic changes which occur in the breasts in connection
with the secretion of milk are described in the next chapter.

The quantity of urine passed during the first two days of the
puerperium is generally above the average. The urine frequently
contains sugar, which may be either glucose or lactose. In the latter
case it is generally believed that the sugar has been absorbed into the
circulation from the changed mammary glands. When glycosuria
occurs, it is probably comparable to post-operative glycosuria (see
p. 539 and pp. 602-604). Albumen may also be present in the urine
in the first days of the puerperium. It is stated further that there
is an increase in the amount of acetone l (see also p. 535).

As mentioned above, a marked leucocytosis occurs during labour.
According to Hofbauer,'2 this becomes still more pronounced during
the first twelve hours of the puerperium, after which the number of
leucocytes in the blood falls again and in a short time becomes

FIG. 160. — Virginal external os FIG. 161. — Parous external os

(human). (From Williams' (human). (From Williams'

Obstetrics. Appleton & Co.) Obstetrics. Appleton & Co.)

normal. Henderson 3 states that on the fifth day the average number
of leucocytes per cubic millimetre is 12,000, whereas immediately
after parturition it is 21,000, as compared with about 8000 in a normal
woman. It is stated that there is a diminution in the number of red
corpuscles during the first days of the puerperium, a circumstance
which is commonly ascribed to the loss of blood at delivery and the
lochial discharge. It is also said that the amount of haemoglobin is
reduced, and that there is a relative increase in the quantity of fibrin
and serum. Experiments show, however, that there is no appreciable
shortening in the coagulation-time of the blood, such as has been
supposed to account for the thrombosis of the sinuses.4

The pulse rate during the early days of the puerperium is usually

1 Scholten, " Ueber Puerperale Acetonurie," Hegar's Beitnige zur Geb. und
Gyndk., vol. iii., 1900.

2 Hofbauer, " Zur Physiologic des Puerperiums," Monatssckr, f. Geburt. uiid
.Gynitk., vol. v., 1897.

3 Henderson, "Observations on the Maternal Blood at Term and during
the Puerperium," Jour, of Obstet. and Gyncec., vol. i., 1902.

4 Longridge, loc. cit.

584 THE PHYSIOLOGY OF REPRODUCTION

stated to be somewhat below the normal, but according to Longridge
such cases are unusual. Williams l says that the pulse is slowest on
the second or third day, after which it becomes quicker, resuming its
normal rate after about ten days.

The temperature is ordinarily normal during the puerperium, the
old idea that the commencement of milk secretion was associated
with a rise of temperature having apparently no basis in fact,
excepting in cases of infection.

Little attention has been paid to the changes which occur during
the puerperal period in other animals. Strahl has shown 2 that the
Mammalia with so-called full placenta (commonly called Deciduata)
can be arranged under three groups according to the process of
puerperal involution of the uterus. In the first group, to which man
and monkeys belong, the epithelium is absent from the mucosa, and
requires, therefore, to be re-formed in the manner described above.
In the second group the placenta is spread out over the inside of the
uterus as in the first group, but in addition to this the inside of
the organ is covered by a layer of epithelium. This arrangement is
found in Carnivores. In the Rodents we often meet writh the third
form; here, towards the end of gestation, not only is the womb
covered with cell-tissue, but this epithelium also runs from the
fimbrisa right underneath the placenta, undermining it till it is finally
only adhering to the walls of the uterus by a slender cord carrying
the vessels. It is evident, therefore, that the uteri of the second
and third groups will resume relatively quickly their non-puerperal
appearance. The principal changes that occur are the reduction of
the surface epithelium both by the casting off of superfluous parts
and by the changing of larger cells into smaller ones, the advance of
new epithelium to cover places that were bare,3 and the reduction
and consolidation of the connective tissue. The latter process is
effected by the cells becoming more compact, as in the bitch, or by
a reduction in the amount of intercellular substance, as in the
hedgehog.4 The puerperal changes in Tarsius are said to resemble
those of Rodents.5 Excepting in those animals which belong to the
first group mentioned the lochial discharge is either very slight or
absent altogether.

The changes which take place in the uterus after abortion have

1 "Williams (Whitridge), loc. cit.

2 Strahl, " The Process of Involution of the Mucous Membrane of the Uterus
of Tarsius spectrum after Parturition," Proc. Section of Sciences, Koninklijke
Akademie van Wetenschappen te Amsterdam, vol. vi., 1904.

3 Duval, "De la Regeneration de 1'Epithelium des Corne ut6rine apres la
Parturition," C. R. de la Soc. de BioL, vol. ii., Series 9, 1890. <

4 Strahl, " The Uterus of Erinaceus europwus after Parturition," Proc. Sect.
Sciences, Kon. Akad. Wet. Amsterdam, vol. viii., 1906.

5 For the puerperal changes in Tvpaia see van Herwerden, loc. cit.

INNERVATION OF THE GENERATIVE ORGANS 585

been studied by Weymeersch,1 who states that the placenta may for
a time persist. If the abortion is produced experimentally by the
removal of the ovaries the absence of the corpus luteum results in an
immediate contraction of the uterine vessels as well as of the uterine
muscle wall. Fortayn2 also states that the chorion survives after
the death of the embryo in the. mouse.

The changes which take place in connection with the formation
of milk in animals are described in the next chapter.

1 Weymeersch, " Etude sur le Mechanisme de 1'Avortement, etc." These.
University de Bruxelles, Paris, 1911. See also Jour, de VAnat. et Phys.,
vol. xlvii., 1911.

- Fortayn, " The Involution of the Placenta in the Mouse after the Death
of the Embryo," Arckiv. de Biol., vol. xxx.. 1920.

19 A

CHAPTER XIII
LACTATION

" Nunc femina quaeque,

Cum peperit, dulci repletur lacte, quod omnis
Impetus in mammas convertitur ille alimenti."

— LUCRETIUS.

THE possession of mammary glands is an essentially mammalian
character. Their function is to provide nourishment for the newly-
born young. They are present in both sexes, but are usually
functional in the female only. Their number and position vary
considerably in different species. There may be only a single pair
(man), or as many as eleven pairs (Centetes). The number in any
particular species usually bears a relation to the normal size of the
litter, or to the requirements of the newly-born offspring. Thus in
the guinea-pig, in which the young are born in an advanced state
of development, and can feed without being suckled, there are only
two mammary glands, while in the rabbit, in which the newly-born
young are naked and helpless and the gestation period is far shorter,
there are seven or eight mammre. In animals which possess a
number of mammary glands, these are usually arranged in two
nearly parallel rows along the ventral side of the thorax and
abdomen. In other cases they are restricted to the thorax (Primates,
excepting some lemurs, Cheiroptera, Sirenia, elephants, sloths) ; while
in others again they are confined to the inguinal region (most
Ungulates, Cetaceans).

In the cow and most other Ungulates the mammae are contained
within a definite milk-bag or udder, which is surrounded by a fibrous
envelope and is suspended below the abdomen. The udder is
provided with milk cisterns or galactophorous sinuses into which
the ducts of the gland open and convey the milk from the secretory
acini. Each sinus communicates with the exterior by a teat, there
being four teats in a cow, corresponding to the four mammary glands
(and sinuses) commonly called the four " quarters." One quarter
may run dry without the others. There is a fibrous division
consisting of yellow elastic tissue between the two lateral halves of
the cow's udder, but not between the anterior and posterior parts.
There are very frequently extra teats (sometimes as many as three)

586

LACTATION 587

situated posteriorly (or one may be between two of the chief teats)
and with glands associated with them. During lactation these extra
glands may secrete, but the milk or other fluid secreted by them,
since it is not usually drawn off, is absorbed into the circulation (see
below, p. 603). In the sheep there are only two glands (lateral
halves), sinuses, and teats (occasionally four), and the mare is similar
excepting that there may be two or even four sinuses opening into
one teat. In the sow the teats extend forward to the thorax in two
rows. In many animals there is a sphincter at the end of each teat.

In Monotremes the mammary glands are stated to be modified
sweat glands, whereas in other mammalian orders they are commonly
regarded as representing sebaceous glands.1 In Monotremes alone
there are no teats, the orifices of the glands being mere scattered
pores in the skin, the exuding milk probably passing along the hairs,
which in this region are arranged in bunches. In Echidna the
orifices open into two depressions which have been called the
mammary pockets.2 Teats, which are present in all other orders
of Mammals, are of two kinds. In one kind the skin in the region
of the gland becomes raised up in a circular rim, and in this. way
gives rise to a tubular teat or nipple, into the base of which the
ducts of the gland open. This form of teat occurs in Carnivora and
Ungulata. In the other kind of teat the gland itself is raised into a
papilla, as in man and other Primates, in Rodents and in Marsupials.
The use of the teats is to facilitate the process of sucking. In the
Cetacea, however, where the action of sucking is incompatible with
the subaqueous life of these animals, the ducts of the mammary
glands are enlarged into reservoirs (somewhat similar to the galacto-
phorous sinuses of Ungulates), from which the milk is ejected into
the mouths of the young by means of a compressor muscle.3

In the male mammal, as just mentioned, the mamm?e do not
usually function, though milk is occasionally produced in man at
birth and at puberty, and more rarely at other times. Male goats
and sheep have been known to yield milk exceptionally, and the
same is also said to be the case with male rats4 (see p. 614).

1 Brouha and certain other authorities regard the mammary glands in all
the Mammalia as modified sweat glands (" Recherches sur les Diverses Phases
du Developpement et de 1'Activite de la Mamelle," Arch, de Biol., vol. xxi.,
1905. This paper contains many references). Eggelung regards the mammary
glands either as homologous with sweat glands, or else as organs which are
sui generis, being derived independently from the primitive merocrine skin-
gland ("Ueber den wichtigen Stadium in der Entwickehtng der menschlichen
Milchdriise," Anat. Am., vol. xxiv., 1904).

2 Wiedersheim, Comparative Anatomy of Vertebrates, Parker's translation,
2nd Edition, London, 1897.

3 Flower and Lydekker, An Introduction to the Study of Mammals, London,
1891.

* Wiedersheim, loc. cit.

588 THE PHYSIOLOGY OF REPRODUCTION

STEUCTURE OF THE MAMMARY GLANDS

The mammary glands are composed typically of a number of
lobes, which are themselves divisible into lobules. Each lobule
consists of connective tissue in which the convoluted ducts of the
gland are bound together. If these ducts are traced backwards they
are seen to arise from groups of secretory alveoli. If they are traced
forwards they are found to unite together to form the lactiferous
ducts, which in the human subject are from fifteen to twenty in
number, and open to the exterior by minute apertures through the
teat. The lactiferous ducts at their point of origin from the lobular
ducts are provided with reservoirs in which the milk collects
during the periods of glandular activity (i.e. during lactation).
These reservoirs in some animals are of a very considerable size (e.g.
whales, as described above). The duct walls consist of areolar tissue
containing some unstriated muscle fibres. They are lined internally
by short columnar epithelial cells which become flattened in the
proximity of the nipple. A quantity of fat generally covers the
surface of the gland, excepting the nipple. This fat is connected
both with the skin in front and with the glandular tissue behind.
Like the latter it is lobulated by processes of areolar tissue. The
nipple also is formed of areolar tissue with unstriated muscle fibres.
It is richly supplied with vessels which give it an erectile structure.
The glandular tissue also is plentifully supplied with vessels, which
vary in size according to the condition of the gland. The glands
in man are innervated by branches from the anterior and lateral
intercostal cutaneous nerves. Sensitive papillte are present on the
surface of the nipple, and around it there is a small area of skin, on
which the ducts of little secretory glands open to the exterior.

In the sow the mammary glands are often pigmented, and the
bacon cut from this area is discoloured, the condition being known
among bacon-curers as " seedy-cut." It was formerly supposed that
the pigment was blood pigment derived from red corpuscles extra-
vasated during "heat," when the glands are apt to be congested,
and that it did not occur in pigs which had been subjected to
ovariotomy. It is now known, however, that the pigment is not
derived from blood (thus, it does not contain iron) and that it may
occur in spayed sows and even in males, but it is always in association
with mammary tissue. It has been identified by Hammond in foetal
pigs in the walls of the developing ducts as they dip down from the
skin. The pigment is presumably identical with that of the hair since it
only occurs in coloured pigs, and in Red Tarn worths is of a sandy colour.1

1 Mackenzie, Marshall, and Hammond, " On Ovariotomy in Sows, etc.," Jour.
Agric. Science, vols. iv., 1911-12 ; v., 1912-13 ; vi., 1914 ; and vii., 1915-16 ; and
"Physiology and Bacon Curing," Jour. Roy. Agric. /S'oc., vol. Ixxvi., 1915.

LACTATION

589

In the secretory cells of the lactating mammary gland an active
and a resting condition can be distinguished. In the latter the
lumina of the alveoli are wide, and the cells of the lining epithelium
form a single flat layer with centrally situated nuclei. In the active
condition the epithelial cells are long and columnar, and project into
the lumina, and some of them have two nuclei.

In these cells numbers of granules and globules accumulate, the
former being probably of a protein nature, and the latter of a fatty
composition. Gradually the alveoli become charged with a fluid
containing detached cells and fatty globules. The detached cells are
usually filled with granules, staining with osmic acid and seemingly

FIG. 162. — Section of mammary gland of woman. (From Sharpey
Schafer, after de Sinety.)

a, Lobule of gland ; b, acini lined by cubical epithelium ; <°, duct ;
#, connective tissue.

identical with the colostrum corpuscles which have been observed to
occur in milk in the first few days after parturition, and occasionally
also at other times. These colostrum corpuscles have been seen to
exhibit amoeboid movements, and so are probably leucocytes which
have wandered into the lumina of the alveoli.1 The secretory fluid
also contains cells which are supposed to have been detached from
the epithelium, but, as will be seen presently, there is some doubt
regarding this point.

The alveoli secrete milk during lactation, not merely while
suckling is going on, but also at other times, so that milk tends to
collect in the ducts and especially in the reservoirs. It has been

1 Sharpey Schafer, "The Mechanism of the Secretion of Milk," Text-Book
of Physiology, vol. i., Edinburgh, 1898.

590

THE PHYSIOLOGY OF REPRODUCTION

calculated that the udder of a cow could not contain the quantity
of milk which can be obtained from it at one milking, so that in
such cases at least it seems certain that the process of secretion must
be carried on during the time that the milk is being drawn.
Furthermore, the milk which is drawn latest has been shown to have
a different composition from that which is first obtained, the proportion
of solids to liquids undergoing an increase as the process of milking
is continued. This, however, is believed to be due partly to the

»••

®r *•'

^^^

^^P^SiS. ^ b

k flp...^4^g,
/••f

FIG. 163. — Section of mammary gland (human) during lactation
(highly magnified), a, Acini ; b, duct.

larger globules of fat meeting with greater resistance in passing
through the ducts and so being retained \intil the end of milking.
Lehmann 1 has recorded an experiment in which a solution of sulphin-
digotate of sodium was injected into a vein of a goat which was
immediately afterwards milked. By the time the udder had been
almost completely emptied, a blue tinge appeared in the milk. After
an interval of about an hour and a half the animal was again milked,
when it was found that the injected sulphindigotate had penetrated
in sufficient quantity to render the milk quite blue.

1 Lehmann, "Beitrage zur Physiologic der Milchbildung," Die landwirth-
schaftlichen Versuchs-Stationen, vol. xxxiii., 1887.

LACTATION 591

Three different hypotheses have been put forward regarding the
manner in. which the substances of which the milk is formed pass out
from the secretory cells. According to one view, the cells themselves
break loose and become disintegrated, setting free their contents in
the alveoli of the gland, just aa in the case of the sebaceous glands.

Another theory states that the cells simply excrete the substances
into the alveolar lumina without becoming detached or destroyed
themselves, as with the submaxillary mucous gland. According to
the third hypothesis the mammary gland in its mode of activity

FIG. 164. — Section of mammary gland (human) in full activity.
(From Sharpey Schafer, after von Ebner.)

«, «',"«", Alveoli variously cut and distended by secretion ; g, g\ commencing
ducts ; ?, connective tissue.

occupies a position midway between the sebaceous and submaxillary
glands ; some of the cells simply discharging their contents into the
lumina, while with others, the central part of the cell, containing a
degenerate daughter nucleus, breaks away and becomes disintegrated,
leaving the basal portion still in position.

It has already been mentioned that the mammary glands of all
Mammals, with the exception of the Monotremes, are usually regarded
as being of the nature of modified sebaceous glands. It was partly
on account of this belief that certain of the older writers held the
view that the secretion of milk was the result of a fatty degeneration

592 THE PHYSIOLOGY OF REPRODUCTION

leading to a complete disintegration of the secretory cells of the
mammary gland.1 According to this theory the colostrum corpuscles
were the detached epithelial cells. In opposition to this theory, it
has been pointed out that there is no evidence of the extensive cell
multiplication, such as would be required in order to supply the large
number of cells which, according to this hypothesis, would necessarily
become detached. Heidenhain2 has shown that if this theory is
correct, the cells of the gland must be completely renewed as often
as five times in one day in order to provide the solid constituents of
the secretion.

The second of the above-mentioned theories receives considerable
support from the circumstance that it has the analogy of the great
majority of secretory glands.3 Moreover, the results of Bertkau's4
investigation point strongly to the conclusion that any appearances of

FIG. 165. — Section through an alveolus with fat drops in cells. (From
Sharpey Schafer, after von Ebner.)

e, Cells of alveolus ; /•, cells of basement membrane (m) ; i, connective tissue.

disintegration which the secretory cells possess are due to imperfect
fixation. This author states that he found no necrobiosis of any
kind in these cells, and he believes that milk formation is a purely
secretory process. This view is now widely accepted and the colostrum
corpuscl.es are regarded as of the nature of wandering leucocytes.

The third theory was first suggested by Langer, and has since
been adopted, with various slight modifications, by Heidenhain,5
Steinhaus,6 and Brouha7 and others. According to their view the

1 Virchow, Die Cellular- Pathologie, Berlin, 1871.

2 Heidenhain, "Die Milchabsonderung," Hermanns ffandbuck der Physiologic,
vol. iv., 1883.

3 Sharpey Schafer, loc. cit.

4 Bertkau, " Ein Beitrag zur Anatomic und Physiologic der Milchdriise,"
Anat. Anz., vol. xxx., 1907.

5 Heidenhain, he. cit.

6 Steinhaus, "Die Morphologic der Milchabsonderung," Arch. f. Anat. u.
Phys., Phys. Abth., Suppl., 1892.

7 Brouha's paper (loc. cit.) contains a full account of the literature.

LACTATION 593

cells of the gland lengthen out, so that their ends couie to project
freely into the lumina of the alveoli. The projecting portions then
undergo a process of disintegration before or after becoming detached,
and the cell substance passes into solution to form the albuminous
and carbohydrate constituents of the milk. The fat droplets which
collect in the disintegrating part of the cell give rise to the milk fat.
The basal portions of the cell remain in position without being
detached, and subsequently develop fresh processes, which in their turn
become disintegrated. It is believed, however, that some cells simply
discharge their fat droplets and other contents into the lumina, while
otherwise remaining intact.1

Steinhaus states that mitotic division of the cell nuclei in the
actively secreting mammary glands is of frequent occurrence, and
that the daughter nuclei which lie in the outer portions of the cells
degenerate and share in the general process of dissociation. Szabo 2
also records the occurrence of two or more nuclei in the same cell
during lactation, and similar evidence of nuclear division has been
observed by others. Moreover, it is argued that this view is in no
way inconsistent with the generally accepted homology between the
mammary and sebaceous glands, since it is easy to understand how,
in the course of evolutionary development, the mode of secretion in
the glands in question might have undergone an alteration, whereby
the process of disintegration in the actively secreting cells became
gradually lessened as the character of the secretion changed. On
the other hand, if we suppose that the cells of the mammary gland
merely extrude their secreted materials without undergoing any
histological disintegration, it is more difficult to uphold the homology
in question. Lastly, it should be mentioned that those who, like
Steinhaus, support the theory of partial disintegration, do not regard
the colostrum corpuscles as detached epithelial cells, as Heidenhain
did, but agree with those who uphold the purely secretory theory in
supposing the corpuscles to be of the nature of " mast cells," or
basophil leucocytes which have wandered inward from the connective
tissue of the gland, as already described, and have made their way
into the lumina of the alveoli.3

1 Brouha, loc. cit. ; also "Les Phenomeaes histologiques de la Secretion
lactee," Anat. Anz., vol. xxvii.

2 Szabo, " Die Milchdriise im Euhezustande und wahrend ihrer Thatigkeit,'
Arch.f. Anat. u. Phys., Anat. Abth., 1896.

3 For references to further literature upon the physiology of milk formation
see Basch, "Die Physiologic der Milchabsonderung," Ergeb. des Phys., 1903,
Jahrg. See also the following for references to the histology : Bizzorzero
and Ottolanghi, "Histologie der Milchdriise," Merkel and Bonnet's Ergeb. d.
Anat. u. Entivick., vol. ix., 1900, and von Ebner, "Von den Geschlechtsorganen,"
Kolliker's Handbuch der Oewebelehre des Menschen, vol. iii., 1902.

594 THE PHYSIOLOGY OF REPRODUCTION

THE COMPOSITION AND PROPERTIES OF MILK

Milk is essentially an emulsion, its white appearance being caused
by the reflection of the innumerable fat globules which it contains in
suspension. These globules, which are from '0015 to '005 millimetre
in diameter, tend to float chiefly at the top, where they help to form
the cream, or that part of the fluid which is richest in fatty
constituents. The specific gravity of both human and cow's milk is
from about 1*028 to i'034.1 When the cream is skimmed off the
specific gravity of course rises.

It is not proposed in the present work to deal more than very
briefly with the composition and properties of milk in different
animals.2 Human milk and cow's milk have been most fully investi-
gated, and it will suffice in this place £o give a short account of their
respective constituents.

The average composition of cow's milk as compared with human

milk is as follows : —

Cow's. Human.

Water- - 88'3 88'8

Proteins 3'0 TO

Fats - 3'5 3'5

Carbohydrates 4'5 65

Salts - --- 07 0'2

lOO'O 100-0

The proteins of milk are caseinogen, lactalbumen, and lacto-
globulin. Of these caseinogen is the most important. This is the
substance which is acted on by the ferment of rennet, producing the
well-known clotting or curding of milk, when the caseinogen is
converted into whey albumen and insoluble casein. Lactoglobulin
and lactalbumen are only present in small quantities.

The fats of milk, which occur in small globules as just described,
are olein, palmatin, and stearin, with small quantities of butyrin,
capronin,and other fats of lower composition. Lecithin and cholesterin
are also present in small amounts, at any rate in cow's milk. The
percentage of volatile fatty acids is less in human than in cow's milk.

Lactose or milk-sugar is the carbohydrate of milk, but other
carbohydrates (animal gum, dextrin, etc.) have also been stated to
occur. Lactose under the influence of certain micro-organisms
becomes converted into lactic acid, which causes the souring of
milk.

Milk is rich in calcium and potassium salts (especially in calcium
phosphate), but magnesium, sodium, and other salts (chiefly chlorides)
are also present in small quantities. The amount of iron in human

1 Halliburton, "The Chemical Constituents of the Body and Food," Sharpey
Schafer's Text-Book of Physiology, vol. i., Edinburgh, 1898.

2 See Halliburton, loc. cit., and Sharpey Schafer.

(1) Young

(2) Dog's

(3) Dog's

Pup.

Milk.

Serum.

- 8-5

107

2-4

- 8-2

6-1

52-1

- 35-8

34-4

2-1

T6

1-5

0-5

0-34

0-14

0-12

39-8

37-5

5-9

7'3

12-4

47-6

LACTATION 595

milk is very slight, while in cow's milk it is practically absent
altogether.

Bunge l has pointed out that whereas the inorganic salts in milk
are present in different proportions from those found in the blood
plasma, these proportions are almost identical with those occurring
in the young animal. He supposes this similarity to indicate an
adaptation to the needs of the young. This point is illustrated in
the following table, which gives the respective amounts of mineral
constituents present in a hundred parts of ash of (1) the young pup,
(2) dog's milk, and (3) dog's serum.

K20 -

Na20 -
CaO -
MgO -
Fe203 -

PA -

ci -

Small quantities of oxygen, nitrogen, and carbon dioxide gases
have been found in solution both in human and in cow's milk.

The chief difference in the composition of cow's milk as compared
with human milk is the relatively high percentage of proteins, fats.
and salts, and the correspondingly low percentage of lactose present
in cow's milk.

Colostrum is the milk which is secreted during the first two or
three days after parturition. It contains less caseinogen than
ordinary milk, but considerable quantities of albumen and globulin
enter into its composition. It coagulates on boiling. The char-
acteristic colostrum corpuscles have already been described.

The mammary glands of newly- born animals sometimes secrete
small quantities of what is popularly called " witches' milk." This
secretion contains most of the constituents of normal milk, but the
solid substances are usually less in amount. It has an alkaline
reaction.2

1 Bunge, Lehrbuch der Physiologischen und Pathologischen Chemie, Leipzig,
1887, and various original papers. Cf. Abderhalden, "Die Beziehungen der
Wachsthumsgeschwindigkeit der Sauglinge zur Zusammensetzung der Milch,
etc.," Zeitsch. f. physiol. C/tem., vol. xxvi., 1899, and other papers by the same
author in the same journal (vols. xxvi. and xxvii.). For further references
see Lusk, The Science of Nutrition, Philadelphia, 1906. It is stated also that
the rennin of the stomach is specifically adapted for the coagulation of the
casein produced by the female of the same race.

2 For fuller information about the constituents and properties of milk, with
tables of composition for different animals, and numerous references to the
literature, see Halliburton, loc. cit. See also Raudnitz, " Bestandteile, Eigen-
schaften und Veranderungen der Milch," Ergeb. der Phys., 1903, Jahrg. 2,
where certain later papers are referred to ; and Abderhalden, loc. cit.

596 THE PHYSIOLOGY OF REPRODUCTION

THE INFLUENCE OF DIET AND OTHER FACTORS ON THE
COMPOSITION AND YIELD OF MILK

The composition of the milk in any one species is subject to
some amount of variation, which is due to various causes. Thus,
the differences in the composition of cow's milk are said to depend
on the following factors : (1) The breed, (2) The advance in the
period of lactation, (3) The season of the year, (4) The length of
the interval between the times of milking, (5) The occurrence of
sexual excitement, (6) Situation and climate, (7) Meteorological
changes, and (8) The character of the food.1 These factors may
now be briefly discussed.

That the yield and composition of the milk varies in the different
breeds is generally admitted. Thus Jersey cows yield a larger
proportion of butter fat than Ayrshires. Within the limits of the
breed also there is great individual variation and heredity plays an
important part.2 But of all the factors enumerated above, diet is
perhaps the most important. The richest and also the most
abundant supply of milk is usually yielded when the food supply
is liberal. As a result of giving food rich in protein substances,
the milk supply tends to contain a larger quantity of protein, sugar, and
fat (especially the latter). Sharpey Schaf er has pointed out, however,
that because an excess of a particular organic principle in the food
causes an increase of certain constituents in the milk, it must not
.be supposed that these constituents are necessarily formed directly
from such material, " for the effect may be produced indirectly by
the functions of the gland-cells becoming modified, according to
the nature of the pabulum they are receiving. Looked at in this
light, certain substances may be said to stimulate the cells of the

1 Crowther, Milk Investigations at Garforth, Leeds, 1904. Droop Richmond,
"The Composition of Milk," Analyst, vol. xxxi., 1906. Lauder, "The Variation
in the Composition of Milk," Bulletin XI. issued by the Edinburgh and East
of Scotland College of Agriculture, 1906. Crowther, "The Chemical Composition
of Butter," Trans. Highland and Agric. >Soc., vol. xix., 1907. Gilchrist and
Jones, " Dairy Investigations in the North-East of England," Trans. Highland
and Agric. Soc., vol. xviii., 1906, and vol. xix., 1907.

2 Gavin has dealt with the question of estimating a cow's milking capacity
by her first lactation yield, and has come to the conclusion that with cows
giving a fairly high or fairly low first lactation revised maximum, this figure
should be used to determine whether they should be kept or not, but with
cows giving a medium first lactation revised maximum, it is worth waiting to
obtain the increased accuracy of an estimate based on the mean between the
first and second lactation revised maxima. (The " Revised Maximum " is
defined as the maximum day-yield of the lactation which is three times reached
or exceeded, i.e. the highest figure common to the three highest day-yields of
a lactation.) Gavin thinks that the maximum yield is a better indicator of
physiological capability than the average yield, and therefore a better guide as
to whether a cow should be kept. ("Studies in Milk Records," Jour. A<j, •',>•.
Science, vol. v., 1913.)

LACTATION 597

glands to increased activity in all directions, tending to the pro-
duction of a larger quantity of milk rich in all kinds of solid
constituents; whilst other substances may be looked upon as
stimulating the cells in a special manner, tending to the increased
production of certain only of the constituents of the milk." 1

According to Crowther's researches on cows, change from a
highly nitrogenous diet to one relatively poor in nitrogen causes
secretion of a greater quantity of milk, but there is a decrease in
the fat content, this being more pronounced in the morning than
in the evening milk. A change in the reverse direction effected an
improvement in the quality of the milk. Concentrated food given
either in the morning or evening tended to increase the fat content
of the morning milk, but had little or no effect upon the evening
milk. These alterations were found to persist without appreciable
diminution for fully five weeks after the change of treatment.

There are a number of preparations in the market, known as
galactogogues, which are said to increase the flow of milk in women,
but, according to Williams, any virtue which they possess is due
largely to the quantity of fluid which is taken with them.2 It is
stated also that certain particular food-stuffs have a very appreciable
effect upon the quantity and quality of milk in cows. Thus bean-
meal is said to increase the flow of really good milk, unless it is
given in immoderate quantities. Brewers' and distillers' grains are
likewise described as having a beneficial influence upon the milk
supply, but if given too freely they tend to injure the breeding
capacity, and in consequence are most used in town dairies where
the cows are not bred from.3 Many substances ingested by the
mother pass unaltered into the milk. It is well known that certain
foods (e.g. turnips) cause an unpleasant taste or smell in the milk
of cows to which they are supplied. Lehmann's experiment, in
which sodium sulphindigotate was injected into the veins of a
goat, and shortly afterwards made its appearance in the milk, has
already been referred to (p. 590). So also it has been found that
immunity from disease may be acquired by young animals being
suckled by a female which had previously become immune, the
antibody to the disease being absorbed in the ingested milk.

It is generally recognised that the nature of the surroundings
has an influence over the mammary secretion. For example, the

1 Sharpey Schafer, loc. cit. There is evidence also that an abnormal diet
during and previous to pregnancy may arrest the normal mammary develop-
ment. See Watson (B. P.), "The Effect of a Meat Diet on Fertility and
Lactation," Proc. Roy. Soc. Edin., vol. xxvii., 1907. For general literature see
Meigs, "Milk Secretion as Related to Diet," Physiological Jieviews, vol. ii., 1922.

- Williams (W.), Obstetrics, London, 1904.

3 Wallace (R), Farm Live Stock of Great Britain, 4th Edit., Edinburgh, 1907.

598 THE PHYSIOLOGY OF REPRODUCTION

composition of the fat in the milk of cows varies with the condition
of the animals. Circumstances tending to cause discomfort usually
lower the proportion of volatile acids present in the butter fat, but
the variation in the composition is very irregular, and appears to
depend partly upon the nervous temperament of the cow. Extremes
of heat and cold are said to produce a decrease in the percentage of
volatile acids, a fact which has been put forward as an explanation
of the general poorness in these compounds of butters from Siberia
and other cold climates. Unseasonable and inclement weather is
believed to have a similar influence.1

In women exercise in the open air may not infrequently increase
the flow of milk. Nervous and mental- influences or any cause which
affects the general metabolism may so change the character of the
secretion in women as to make it no longer fit for the child.
Violent emotion or shock have been known to lead to the complete
suppression of the mammary secretion.2 The employment of certain
drugs also influences it. Thus atropine, if given in sufficient
quantities, stops the secretion altogether, or if supplied in smaller
amounts causes the milk to become more concentrated.

The occurrence of menstruation in women, or of heat in certain
animals, may have a deleterious influence upon the milk, and so
upon the offspring (see p. 362). In the case of cows, oestrus generally
has a marked effect on the milk-yield, which as a rule shows at first
a perceptible diminution, followed usually at the next milking by a
yield well above the average. The fat content is generally at first
considerably reduced, but at the following milking is sometimes
abnormally high, or may be still abnormally low. On the two or
three days preceding the outward manifestations of heat, the fat
content tends to be decidedly above the average.

Ovariotomy is stated to have a beneficial effect upon goat's milk,
relieving it of the characteristic hircine odour, increasing the quantity
of butter, casein, and phosphoric acid (though decreasing the lactose
present), and producing a greater and more long-continued secretion.3
The removal of the ovaries in cows may also tend to improve the
quality of the milk, rendering it 'richer than when the animals have
been some months pregnant.4

The advance of lactation may be. accompanied by changes both
in the amount and in the composition of the mammary secretion,
but the changes vary greatly in different individuals. In cows, the
milk fat secreted in the first few days after parturition is poor in

1 Crowther, loc. cit.
- Williams, loc. cit.

3 Oceanu and Babes, " Les Effets Physiologiques de 1'Ovariotomie," C. R. de
VAcad. des Sciences, vol. cxl., 1905.

4 Wallace, loc. cit.

LACTATION 599

volatile acids, but it tends to improve rapidly during the first few
months, the improvement being maintained until near the close of
the lactation period, i.e. in most cases near the approach of the next
parturition.1

It is well known that there is a change in the amount of milk
produced by a cow as it grows, older. Pearl has dealt with this
matter statistically and has arrived at the following general con-
clusion: "The amount of milk produced by a cow in a given
unit of time (seven days, one year, etc.) is a logarithmic function
of the age of the cow."

The law may be stated verbally in the following way : Milk flow
increases with increasing age but at a constantly diminishing rate
(the increase in any given time being inversely proportional to the
total amount of flow already attained) until a maximum flow is
reached. After the age of maximum flow is passed the flow
diminishes with advancing age and at an increasing rate. The
rate of decrease after the maximum is, on the whole, much slower
than the rate of increase preceding the maximum. In general the
law above stated applies to the absolute amount of fat produced in
a unit time as well as to the milk. 2 These conclusions agree with
those of Gavin.

THE DURATION OF LACTATION

The duration of the lactation or nursing period in the different
species of animals is governed mainly by the needs of the young. In
such animals as the guinea-pig, in which the young are born in a
sufficiently advanced state of development that they are able to fend
for themselves, the length of the lactation period is relatively short
and inconstant, while in other animals, belonging to the same order
of Mammals, the young are born helpless, and are dependent for
some weeks upon their mother's milk. In the larger animals the
period of nursing is of course longer, but in them also its average
duration appears to depend largely upon the necessities of the
offspring.

The natural period of lactation in the cow is between nine and

1 In cows which are "drying off," the percentage of volatile acids in the
butter fat is very low. See Crowther, loc. cit.

2 Pearl, "On the Law Eelating Milk Flow to Age in Dairy Cattle," Proc.
Soc. Exp. Biol. and Med., vol. xii., 1914. See also Pearl, "The Change of Milk
Flow with Age," Agric. Exp. State Papers, Orono, Maine, 1917 ; and Gowen,
"Studies in Milk Secretion," V. and VI., Genetics, vol. v., 1920. These papers
give numerous references. For further information about variation in quantity
and quality in milk of dairy cattle see papers by Pearl and by Gowen, Jour, of
Agric. Research, vols. xvi. and xvii., 1919, and Gowen, Jour, of Dairy Science,
vol. iii., 1920. For "Transmission or Inheritance of Milking Capacity"
see Gowen, Jour, of Heredity, vol. xi., 1920.

6oo THE PHYSIOLOGY OF REPRODUCTION

ten months, allowing for an interval of from two to three months to
prepare for the next milking period. The duration of the period in
any given animal depends to some extent upon such factors as diet
and general treatment as described above, but there is much
individual variation. Some cows continue to give milk until the
next calving, but without a rest they are liable to yield a less
abundant supply in the succeeding year.1 Gavin 2 shows that in the
absence of gestation the average milk yield falls from the maximum
to about forty-five per cent, forty-two weeks after calving. One
cow, however, was sold in milk sixty-three weeks after calving. If
gestation intervenes the lactation-time is on the average very
much shorter. The milk yield begins to drop about nine weeks after
service, and once the reduction begins the rate of fall is steady.

It follows that a new gestation period in the cow has no arresting
influence over the mammary secretion. Cows which have been
castrated during lactation may yield milk for years without any
cessation, and thus give on the aggregate a larger supply than cows
which calve annually in the ordinary way. It is well known that
constant milking acts as a stimulus to the secretory activity, and
that cows which are not milked soon " run dry."

In the human female a year may be regarded as the normal
period of nursing, any longer time involving what is known as
hyperlactation. The practice of hyperlactation is said to be common,
but it is to be deprecated in the interests of the infant.3 It would
appear that if continuous suckling is encouraged, the supply of milk
in strong, healthy women may last almost indefinitely. As already
mentioned, menstruation not infrequently commences to recur during
the lactation period, and the latter may overlap gestation until
within a short time of delivery.

THE DISCHARGE OK MILK

The discharge of the milk from the lactiferous ducts which occurs
during sucking is due partly to the direct mechanical pressure, and
partly to the action of the muscular tissue which is present in the
walls of the ducts and in the nipple. The muscular mechanism
appears to be stimulated reflexly by the action of sucking. The
contraction of the muscles in the nipple causes this structure to

1 Wallace, loc. cit.

2 Gavin, "Studies in Milk Records," I., Jour. Agric. Science, vol. v., 1913.
Gavin's results were obtained from a study of the data accumulated by the late
Lord Eayleigh and the Hon. E. G. Strutt at Terling for twenty years.

3 Dingwall Fordyce, "An Investigation into the Complications and Dis-
abilities of Prolonged Lactation, etc.," an extension of papers published in the
Lancet, the British Medical Journal, and the British Journal of Children's
Diseases, 1906.

LACTATION 601

stiffen, and it is suggested that this action has the effect of keeping
open the orifices of the ducts, and thus permitting the free outflow
of milk.1

It is probable also that the discharge of the secretion is assisted
in some degree by the swelling of the entire mammary gland
resulting from a reflex dilatation of the vessels ; but if the secretory
process is very active, and the ducts are heavily charged, the flow
of milk may take place almost automatically, and with hardly any
external stimulus.

THE FORMATION OF THE ORGANIC CONSTITUENTS OF MILK

The principal organic constituents of milk are peculiar to the
secretion, a fact which shows that they are elaborated in the
mammary glands themselves, and not elsewhere in the body. It is
stated, however, that a relatively small amount of caseinogen is
present in the secretion of the sebaceous glands, from which, as
already remarked, it is commonly supposed that the mammary
glands2 have been derived in the course of evolution. Nothing
appears to be known definitely regarding the method of formation of
the caseinogen of milk,3 but it has been suggested that it is derived
from the degenerate nuclei of the gland-cells.

The precise method by which the milk fat is formed is likewise
unknown. It may be derived from protein material, the change
being effected in the cells of the gland, or some of it may possibly
have its source in fat which has already been formed elsewhere, and
carried to the mammary glands in the blood or lymph. There is no
reason for supposing that the cells of the glands do not possess, in
common with most other tissues, the power to elaborate fat. On the
other hand, there is definite histological evidence that they have this
capacity (see above, p. 593). Moreover, the special composition of
the milk fat seems to be by itself conclusive evidence that it is
constructed within the mammary glands.

The suggestion has been made that the leucocytes which migrate
through the epithelium and make their way into the secretory fluid
may help to bring fatty globules into it,4 but there seems no
necessity for assuming that this is the case.

The fat formation which takes place in the cells of the lacteal
glands in the process of milk manufacture has been compared with
the fatty degeneration which occurs in other tissues, milk being

1 Sharpey Schafer, loc. cit.

- Neumeister, Lehrbuch der physiologischen Chemte, vol. ii., Jena, 1895.

:i Thierfelder, "Zur Phvsiologie der Milchbildung," Pfltiger's Arch., vol. xxxii.,
1883.

4 Michaelis, "Beitrage zur Kenntniss der Milchsecretion," Arch. f. Mikr.
Anat., vol. xxi., 1898.

602 THE PHYSIOLOGY OF REPRODUCTION

nothing more than an emulsion of the fat of butter in a solution of
salts, proteins, and sugar. " What occurs as a normal process in the
cells of the lacteal glands occurs under pathological conditions in
much greater extent in very various tissues, and leads almost always
to incurable and fatal losses, since as a rule no reparation is made by
the younger cells." l " The production of milk," says Virchow,2 " in
the brain instead of in the lacteal glands, constitutes a form of brain
softening. The same process that in the one place affords the
happiest and sweetest results, in another induces a painful and bitter
wound." It has already been mentioned, however, that the fat of
milk has a special composition of its own, so that too much stress
must not be laid upon a resemblance between the secretion of milk
and the pathological formation of other fluid substances in different
parts of the body.

The mode of formation of the sugar of milk has been the subject
of some controversy. Bert3 supposed that it was formed from
glucose which was absorbed by the cells of the mammary gland
from the circulating blood. The glucose, according to this view, was
manufactured in the liver, or, at any rate, elsewhere than in the
mammary gland. Bert based his hypothesis upon two experiments
in which the glands were removed from goats- which afterwards
became pregnant. The urine of each animal was tested during
pregnancy to see if any reducing agent was present, but no such
substance could be found prior to the birth of the kid. On the
other hand, for several days after parturition a substance which
reduced cupric sulphate was discovered in each case. Bert concluded
that this was glucose. He supposed further that the reducing body
present in the urine of the two goats represented glucose which in
normal animals would have been converted into lactose in the
mammary glands. The experiments were afterwards repeated by
Moore and Parker,4 who operated likewise upon two goats, and
obtained results which were the direct opposite of those of Bert.
These authors consequently concluded that the complete process of
lactose formation takes place in the cells of the mammary glands.

The question was subsequently reopened by Porcher,5 who also
repeated Bert's original experiment on a goat. After parturition in

1 Verworn, General Physiology, Lee's Translation from the second German
edition, London, 1899.

2 Virchow, loc. cit.

3 Bert, "Sur 1'Origine du Sucre du Lait," C. R. de VAcad. des Sciences,
vol. Ixxxviii., 1884.

4 Moore (B.) and Parker, " A Study of the Effects of Complete Eemoval of the
Mammary Glands in Relationship to Lactose Formation," Amer. Jour, of
PhysioL, vol. iv., 1900.

5 Porcher, "Sur 1'Origine du Lactose," C. R. de VAcad. des Sciences,
vol. cxxxviii., 1904. " De la Lactosurie," Monographies Cliniques, Paris, 1906.

LACTATION 603

the operated animal, an intense glycosuria is said to have occurred,
the phenylhydrazine test showing that the substance present in the
urine was glucose, and not lactose or some other reducing body.
Porcher also removed the mammary glands from four goats and one
cow during lactation, and for a few hours after the operation obtained
marked glycosuria. As a result of these experiments, taken in
conjunction with those of Bert, he concluded that the truth of the
latter's theory was established beyond all doubt.

More recently the writer, working in conjunction with Dr.
Kirkness,1 carried out a series of experiments upon guinea-pigs.
The mammary glands were removed prior to pregnancy (four cases)
or during pregnancy (one case). The urine was tested for sugar
both before and after parturition, but none was found in any of the
experiments. Other experiments showed that glycosuria may occur
after parturition in normal unoperated animals, but that it does
not do so invariably.2 When glycosuria does so take place, its
occurrence is probably comparable to post-operative glycosuria, the
cause of which is not understood. The glycosuria observed by
Porcher after the removal of the mammary glands during lactation
may perhaps be explained as an ordinary post-operative effect, and
cannot be cited as proof of Bert's hypothesis.

According to Thierfelder 3 and Landwehr,4 a formation of lactose
may take place if pieces of fresh mammary tissue are kept in normal
salt solution at body temperature. The lactose is said to be formed
from a precursor which Landwehr identified as " animal gum " or
carbohydrate of low reducing power.

According to Foa, there is a diminution of glucose in the venous
blood coming from the mammary glands, but the amount of glucose
and other carbohydrates present in the blood during lactation is no
greater than in normal blood.5

Muntz6 has put forward the view that the lactose of the

1 Marshall and Kirkness, " On the Formation of Lactose," Biochem. Jour.,
vol. ii., 1906.

2 Puerperal glycosuria and lactosuria have been described in women in
a number of cases. Lactosuria is also stated to occur not infrequently in the
late stages of pregnancy both in women and animals, the lactose in such cases
being presumably derived from the mammary glands by a process of absorption.
So similarly lactose has been found in the urine of cows having accessory glands
and teats from which the milk is not drawn off (see above, p. 587 ; Mackenzie
and Marshall, MS. unpublished). See Hofmeister, " Ueber Laktosurie," Zeitsch.
f. physiol, Chem., vol. i., 1887 ; Porcher, De la Lactosurie, 1906 ; and " L'Origine
du Lactose," Arch. Internat. de Phys., vol. viii., 1909. See also p. 539.

3 Thierfelder, "Zur Physiologic der Milchbildung," Pfliiger's Arch., vol. xxxii.,
1883.

4 Landwehr, "Ueber die Bedeutung des tierischen Gummis," PJliiger's
Arch., vol. xl., 1887.

5 Foa, "Sull' Origine del Lattosio del Latte," Arch, di Fis., vol. v., 1908.

6 Muntz, " Sur 1'Existence des Elements du Sucre de Lait dans les Plantes,"
Annales de Chim. et de Phys., vol. x.

604 THE PHYSIOLOGY OF REPRODUCTION

mammary secretion is formed by the union of glucose, the normal
.sugar of the organism, with galactose, which is supposed to be
derived directly by hydrolysis from certain polysaccharide substances
introduced in the food. It is pointed out further, that such
substances are present in plants which form the normal diet of
certain animals. It would appear, however, that there is no direct
evidence that lactose is actually formed in this way. Moreover,
this theory can scarcely be applied to carnivorous animals, as
Porcher 1 has pointed out.

There is, therefore, no definite evidence that lactose is elaborated
in the mammary glands from any closely related carbohydrate
precursor carried thither from elsewhere in the body. It is more
likely, as Hammond has suggested, that milk-sugar is derived from a
glycoprotein precursor which, mixing with water and salts from
the blood, contributes to the secretory product. As evidence of this
contention he refers to a number of experimental observations by
different physiologists besides recording a series of experiments of
his own. The evidence is summarised in the next paragraphs.

Lusk 2 states that after administering phloridzin (which removes
glucose from the blood by causing it to be excreted in the urine)
to a goat the results were a reduction in the milk yield but an
increase in the percentage of fat. Similarly Porcher,3 experimenting
on cows and goats, obtained a reduction in the milk yield. Paton
and Cathcart,4 by injecting phloridzin, likewise produced a decrease
in the secretion together with a diminution in the lactose, nitrogen,
and ash. When the milk secretion was most reduced the sugar
excreted in the urine was greatest. Rose5 found that the milk
secreted varied inversely with the phytin in the food, and that
when the latter was increased the percentage of fat in the milk
increased.

Hammond & himself found that as a result of injecting pituitary
extract, which acts as a powerful immediate galactogogue (see below,
p. 621), the milk was normal in composition except for an increase
in the fat. (The daily yield was only slightly increased ; thus if the
goat was injected in the morning the milk secreted at that time

1 Porcher, " Sur la Physiologic de la Mamelle," Jour, de Med. Vet. de VEcole
de Lyon, 30th September 1905.

- Lusk, "Ueber Phloridzin-Diabetes," Zeitsch. f. Biol. (Festschr. B. Voit),
1901.

3 Porcher, "L'Origine du Lactose," Arch. Internat. de Phys., vol. viii., 1909.

4 Paton and Cathcart, "On the Mode of Production of Lactose in the
Mammary Gland," Jour, of P/iysiol., vol. xlii., 1911.

5 Rose, " A Study of the Metabolism Effects of Certain Phosphorous Com-
pounds," New York State, State Tech. Bull., 1912.

6 Hammond, "The Effect of Pituitary Extract on the Secretion of Milk,"
Quart. Jour. Exp. PhysioL, vol. vi., 1913. Hammond and Hawk, " Studies in
Milk Secretion," Jour. Agric. Science, vol. viii., 1917.

LACTATION 605

was greath7 increased, but the evening milk was reduced almost in
proportion.) The ratio of nitrogen to lactose in the milk was almost
constant throughout.

As a result of withholding food for a few days, together with an
injection of phloridzin, thereby considerably reducing the nutrition,
the yield of milk could be greatly diminished but the fat percentage
rose. The fat, however, subsequently diminished, possibly as a
secondary effect of the decreased secretion by the gland-cells. On
feeding such animals the milk yield rapidly increased, but the
percentage of fat decreased. Hammond found also that the amount
of milk produced by the action of pituitary extract varied with the
state of nutrition, and he concludes that the fat percentage of the
pituitary milk is increased by a condition of lowered nutrition in
the same way as with normal milk. Further, after injecting
adrenalin the fat percentage in the milk is increased but the actual
quantity of milk is somewhat below the normal.

Taylor and Husband,1 as a result of a recent investigation upon
cow's milk, have reached the following conclusions : The percentage
composition of the milk seems to be determined by its rate of
secretion. The percentages of protein and ash, as well as of fat, vary
inversely, and the percentage of lactose varies directly, as the daily
volume, the greatest variation being shown by the fat and the least
by the inorganic elements. There is an inverse relationship between
the percentage of lactose and the percentages of all the other con-
stituents of the milk, this being particularly apparent in the case
of the fat. Diet has no direct influence on the percentage composi-
tion of the milk, except in the case of the non-protein nitrogen
which is not a product of the mammary gland. Diet has, however,
an indirect influence by reason of its effect on the daily volume. A
high protein diet would appear to stimulate the rate of secretion of
the milk. It is suggested, further, that the quantity of lactose
elaborated by the gland may control the daily volume of milk,
and that therefore the rate of its elaboration is a regulative factor
in the rate of milk secretion.

THE NORMAL GROWTH OF THE MAMMARY GLANDS

The growth of the mammary glands in the rabbit has been
described by Miss Lane-Claypon and Starling, from whose paper the
following account is taken.2

1 Taylor and Husband, "The Effect on the Percentage Composition of
the Milk of (a) Variations in the Daily Volume, and (b) Variations in the
Nature of the Diet," Jour, of Agric. Science, vol. xii., 1922. This paper contains
further references.

2 Lane-Claypon and Starling, " An Experimental Inquiry into the Factors
which Determine the Growth and Activity of the Mammary Glands," Proc.
Roy. Soc., B., vol. Ixxvii., 1906. See also Brouha, loc. tit.

6o6

THE PHYSIOLOGY OF REPRODUCTION

In the virgin animal of about eight to twelve months old
mammary tissue cannot ordinarily be detected with the naked eye,
but in stained preparations of the connective tissue surrounding
the nipple, it is possible to see the ducts which comprise the gland.
These are generally restricted to an area of not more than one
centimetre broad. Sections show that the gland at this stage
consists entirely of ducts which are lined with a single layer of
flattened epithelium, and end blindly. No traces of alveoli are to be
seen in the gland.

By the fifth day after conception a marked change has taken

FIG. 166. — Section of developing mammary gland of horse.
Sharpey Schafer, after Hamburger.)

s, Sebaceous glands ; v, blood-vessels.

(From

place in the gland, which now appears, on reflecting the skin from
the abdomen, as a clearly differentiated pink area, circular in shape,
and surrounding the position of each nipple. The diameter of this
area is from about two to three centimetres. Sections through the
gland show that it still consists entirely of ducts, but that these are
in a state of active proliferation. The epithelial lining no longer
consists of a single cellular layer, but is two or three cells deep,
while the individual cells are more swollen than those of the virgin
gland, and mitotic figures are commonly seen.

The mammary gland now grows rapidly, so that on about the
ninth day after conception, on reflecting the skin from the abdomen,

LACTATION

607

the entire surface is found to be covered with a layer of glandular
tissue, the margins of the individual glands being practically
contiguous, each of them having a diameter of from five to eight
centimetres. Sections show that the formation of alveoli (i.e. definite
secretory structures) has begun at this period, especially at the
periphery, where the gland is generally somewhat thicker than in
other parts.

From this stage onwards the growth of the ducts and the
formation of alveoli proceed rapidly, so that by the twenty-fifth day

FIG. 167. — Section of mammary gland (human), showing developing alveoli.
(From Sharpey Schafer, after von Ebner.)

b, Connective tissue ; d, undeveloped alveoli ; d', partially developed
alveoli ; g, blood-vessel ; m, portion of duct.

of pregnancy the whole surface of the abdomen has become covered
by mammary gland tissue, which may be half a centimetre thick.
This tissue is seen in sections to consist for the most part of alveoli,
in the cells of which fat globules are in process of formation.

From about the ninth day onwards to the twenty-fifth it is usually
possible to squeeze a watery fluid from the nipples. During the last
days of pregnancy this fluid assumes the characteristics of normal
milk, so that by the time of parturition, which occurs in the rabbit
on the thirtieth day after conception, the glands are full of milk.

The multiparous rabbit differs from the virgin in possessing
ready-formed alveoli at the beginning of pregnancy. Consequently

608 THE PHYSIOLOGY OF REPRODUCTION

the amount of mammary growth during the gestation period of the
multiparous animal is relatively less.

The changes which take place in the human female and in other
animals during pregnancy are in a general way similar to those
occurring in the rabbit. In women after the second month the
breasts are said to offer a nodular sensation on palpation, this being
due to the hypertrophy of the mammary alveoli. The nipples also
enlarge, and at the same time become more erectile and pigmented,
while the areola surmounting the nipple becomes broader and
pigmented also, in dark individuals being often almost black. The
hypertrophy of the sebaceous glands in the areola results in the
formation of the so-called glands of Montgomery, which appear as
small round elevations. As already mentioned, during the later
months of pregnancy the thin yellowish fluid known as colostrum
can generally be expressed from the nipples.

The mammary glands are said to undergo growth at puberty, and
there can be no doubt that a slight hypertrophy generally takes place
in connection with each period of prooestrum and oestrus. These
changes must be ascribed to ovarian influence, which, as has already
been proved, is responsible for the changes which occur at such times
in the other generative organs, while, as shown below, the mammary
growth which takes place after ovulation is due to the corpus luteum.
Gellhorn l refers to a case of a woman who had abnormal mammary
glands with seven nipples in the neighbourhood of the mons veneris,
and who yielded milk at each menstrual period. Other similar cases
have been recorded. This phenomenon is, of course, contrary to the
more usual tendency for menstruation to be in abeyance during
lactation.

THE FACTORS WHICH ARE CONCERNED IN THE PROCESSES
OF MAMMARY GROWTH AND SECRETION

It has just been mentioned that the mammary glands in the
female begin to undergo enlargement at the period of puberty in
correlation with the increase in ovarian activity. In man the
difference between the glands in the two sexes is first manifested at
this time. The slight hypertrophy which occurs in connection with
each prooastrous period has been referred to, while the great growth
which the glands undergo during pregnancy has also been described.

It was formerly supposed that there was a direct reflex connection
between the growth of the mammary glands and the development
of the embryo in the uterus, the hypertrophy of the glands
being determined through the intermediation of the central nervous

1 Gellhorn, "Abnormal Mammary Secretion," Jour. A me/: Ned. Assoc.,
21st November 1908.

LACTATION 609

system. There is now, however, abundant evidence that such is
not the case. This is shown, for example, by the experiment
performed by Goltz and Ewald,1 which has already been referred to
in considering the factors concerned in parturition. The lumbo-sacral
part of the spinal cord was completely exsected in a pregnant bitch,
so that all possible connection between the mammary glands and
pelvic organs through the nervous system was destroyed. Pregnancy
was accompanied as usual by mammary development, and after
parturition, lactation occurred normally. Routh's case,2 in which
normal lactation took place in a woman with complete paraplegia
below the level of the sixth dorsal vertebra, has also been referred to
(p. 571). Moreover, it has been shown by Eckhard3 that after
complete severance of the nerves (branches of the external spermatic)
passing to the mammary gland, the activity of the latter, and
consequently the supply of milk, are in no way affected.4

Further evidence in support of the conclusion that the connection
between mammary and fostal growth is not nervous in character is
supplied by those experiments in which portions of gland were
successfully transplanted to abnormal positions in the body. Thus
in an experiment on a guinea-pig Eibbert 5 grafted mammary tissue
from the normal position to the neighbourhood of one of the ears.

1 See pp. 514 and 571.

2 Routh, " Parturition during Paraplegia, with Cases," Trans. Obstet. Soc.,
vol. xxxix., 1897.

3 Eckhard, Beitrdge zur Anat. u. Phys., vol. i., Giessen, 1855.

4 Eckhard's experiments have been repeated by others with somewhat
contradictory results (see Basch, loc. cit.) ; Rb'hrig (" Experimentelle Unter-
suchungen iiber die Physiologic der Milchabsonderung," Virchow's Archiv,
vol. Ixvii., 1876) found that the external spei-matic nerve contained vaso-
motor fibres for the vessels of the mammary gland, and that these affected its
secretory activity by controlling the blood supply. Mironow (" De 1'Influence
du Systeme Nerveux des Glandes Mammaires," Arch, des Sciences Diol. de
St. Petersbourg, vol. iii., 1894) states that artificial stimulation causes a reduction
in the quantity of secretion. He states further that whereas section of the
external spermatic on one side has no effect on the secretion, section on both
sides diminishes it, but that the diminution only comes on gradually after a
number of days. After complete severance of all the nerves in pregnant
animals the glands may continue to grow and yield milk after parturition.
Basch (loc. cit.) states that extirpation of the cteliac ganglion or transection of
the spermatic nerve does not inhibit the secretory process, but increases the
number of colostrum corpuscles. There is abundant evidence of a general
kind that the central nervous system in some way exerts an influence on the
mammary gland. Thus the effects of nervous shock in altering or inhibiting
milk secretion in women are well known. Moreover, the occurrence of uterine
contractions on putting the child to the breast, and so stimulating the nipples,
is evidence of a nervous connection. It would seem probable, therefore, that
though the mammary gland is essentially an automatic organ, the connection
of which with the generative organs is through the vascular- rather than the
nervous system, yet it is under the regulating control of the latter by means
of secretory or vasomotor fibres.

5 Ribbert, "Ueber Transplantation von Ovarium, Hoden und Mamma,"
Arch. f. Entwick.-Mechanik, vol. vii., 1898.

6io THE PHYSIOLOGY OF REPRODUCTION

Notwithstanding the fact that the transplanted gland had lost its
normal nervous connections, it underwent enlargement during a
subsequent pregnancy, and afterwards secreted milk. Pfister 1 states
that he performed a similar experiment on a rabbit, and obtained
a similar result.

The inference is, therefore, that the relation between the growth
of the mammary glands and the development of the foBtus in the
uterus is chemical in nature.

Lombroso and Bolaffio2 have described an experiment in which
two female rats were grafted together so that their respective
circulatory systems were presumably united. Subsequently to their
union they each became pregnant, but at different times. They
afterwards produced young, one prematurely, and the other at full
term. The mammary glands of each underwent the characteristic
changes, but they occurred independently and not synchronously.
The authors cite this result as evidence against the foetal hormone
theory. Moreover, as a result of this and another similar experiment,
they conclude that parturition is not induced by a chemical excitant
circulating in the blood (see p. 574).

On the other hand, in the case of the Bohemian pygopagous
twins, Rosa-Josepha, the mammary glands of both are described as
having been similarly and simultaneously affected by the pregnancy
of Kosa, who bore a healthy boy on April 17, 1910. Milk was
afterwards secreted by the breasts of Josepha as well as of Rosa,
although Josepha had never conceived.3

As Miss Lane - Claypon and Starling have pointed out, the
phenomenon of fertilisation succeeded by foetal growth involves
the occurrence of changes in the ovaries and in the uterus (both in the
muscle and in the mucous membrane), as well as the formation of an
organ of complicated structure — the placenta — the function of which
is to nourish the developing young. The question arose, therefore,
as to whether the foetus or either of the above-mentioned organs was
not the direct source of formation of a hormone or chemical excitant
which, after circulating in the blood-stream, acted as a stimulus to
mammary growth. t

1 Pfister, " Ueber die reflektorischen Beziehungeu zwischen Mammae und
Genitalia inuliebria," Beitruge zur Geb. und Gfynak., vol. v., 1901.

2 Lombroso and Bolaffio, "La Parabiosi- e la Questione del Fattori che
determinano la Fuz Funzione mammalia e 1'Insorgenza del travaglio di parto,"
Atti delta 8oc. Ital. di Obstet. e. Gin., vol. xv., 1909.

3 British Med. Jour., Part II., 28th May 1910. The twins were described
as being united posteriorly by a common sacrum, but the iliac bones were
separate. There was a common anus, perineum, clitoris, and nieatus urinarius,
but the labia majora were double. The urethra was single for an inch above
the meatus, but then it bifurcated. The ureters were normal. The desire to
micturate was said to be distinct, but not the desire to defaecate. The twins
died at the same time in April 1922.

LACTATION 611

It has been shown that milk can be secreted if the ovaries are
removed in the latter part of pregnancy, but it is not clear whether
the secretion begins immediately after ovariotomy or whether it is
postponed till after parturition.1

It is known that the mammary glands undergo normal development
in cases of extra-uterine foetation in which the growth of the uterus
is relatively small. This observation clearly indicates that the
source of the stimulus in question is not to be sought in the hyper-
trophied uterus. A consideration of these and other facts led Miss
Lane-Claypon and Starling to the conclusion that one or other of the
products of conception (i.e. either the foetus or placenta), or possibly
both, were the seat of origin of the specific chemical stimulus
which brought about mammary growth.

Halban2 had recently formed the opinion, chiefly on clinical
grounds, that the specific stimulus arose mainly in the chorionic villi
and placenta.

Ancel and Bouin have suggested that the stimulus for mammary
growth in the later part of pregnancy is produced by the so-called
myometrial gland which is said to be located in the muscular layers
of the uterus, but according to other observers there is no evidence
for this suggestion (see below, p. 618).

The Fcetal Hormone Theory. — Miss Lane-Claypon and Starling
appear to have been the first to deal with the problem experimentally.
In an initial series of experiments they injected extracts or emulsions
of ovaries obtained from pregnant rabbits into other rabbits either
sub6utaneously or intraperitoneally. In two further series of experi-
ments rabbits were injected with uterine and placental emulsions or
extracts. In no case, however, did the injections produce any effect
on the mammary glands, although in certain of the experiments in
which ovarian or uterine substance was employed, marked swelling
and congestion of the uterus were afterwards observed.

The effect of injecting foetal extract was next tried, and this led
apparently to positive results. When repeatedly injected into female
rabbits the extract seemed to produce a genuine development of
the mammary glands which simulated the normal growth which
occurs during pregnancy. In one case a virgin rabbit received fifteen
injections of extract made from many embryos of the same species.
The injections were spread over a fortnight, at the end of which the
rabbit was killed. It was found that a secretory fluid could be
expressed from the nipples, and that on reflecting the abdominal skin
all the mammary glands had grown to the size which is ordinarily

1 Marshall and Jolly, "Contributions, etc.," Phil. Trans., B., vol. cxcviii.,
1905.

2 Halban, " Die innere Sekretion von Ovarium und Placenta und ihre
Bedeutung fur die Function der Milchdriise," Arch. f. Gynak., vol. Ixxv., 1905.

612 THE PHYSIOLOGY OF REPRODUCTION

reached in a rabbit about eight days pregnant. In another rabbit
which received twenty-four injections, spread over five and a half
weeks, the effects produced were still more marked. Further experi-
ments showed that boiled extract was as effective as unboiled, and
the conclusion was therefore drawn that in all probability the specific
secretion or hormone is capable of withstanding boiling. It was
shown also that the substance in question could be obtained equally
well from different parts of the foetus, that it passes through a
Berkefeld filter, and that it is not retained to any appreciable
extent by the kieselguhr in Buchner's method for extracting cell
juices.

Foa states that extract of ox foetus, when injected into rabbits,
produced development of the mammary glands. He concluded,
therefore, that the stimulating substance which causes mammary
growth is not specific — i.e. not peculiar to any one kind of mammal.
Foa says also that if the extract is heated to 110° the active substance
is destroyed, and no result is produced by injection.1

Since the growth of the mammary glands was apparently due to
a specific chemical stimulus arising in the foetus, it was natural to
suppose that the beginning of the actual secretory process which
marks the cessation of growth was caused by the removal of this
stimulus — in other words, by the expulsion of the foetus. In this
connection it is interesting to note that abortion or premature
labour is often followed by the appearance of milk in the
breasts.

The idea that lactation is due to the removal of an inhibition
appears to have been entertained first by Hildebrandt,2 who put
forward the suggestion that the developing embryo exerts an
influence whereby the cells of the mammary gland are protected
from those autolytic disintegrative processes which are supposed to
occur during active secretion. That the act of secretion is to be
ascribed to autolytic processes of the gland, is, according to Miss
Lane-Claypon and Starling, highly improbable, and there is no
evidence that the autolysis of the gland-cells would give rise to the
specific constituents which characterise milk.

Halban 3 has put forward the view that the specific stimulus for
mammary development arises in the placenta, while the active
secretion of the mammary glands is determined by the expulsion or

1 Foa, "Sui Fattori che determinano 1'Accrescimento e la Funzione della
Ghiandola Mammalia," Arch, di Fis., vol. v., 1908.

- Hildebrandt, "Die Lehre von der Milchbildung," Hofmeister's Beitrage,
vol. v., 1904.

3 Halban, loc. tit. See also Bouchacourt, C. R. de la Soc. de Biol., 1902 ;
and Lederer and Przibram, Pfliiger's Arch., vol. cxliv., 1910. The latter authors
found that extract of placenta injected into a goat caused a marked increase in
milk, while ovarian extract had no effect.

LACTATION 613

death of the placenta.1 Keiffer,2 on the other hand, has entertained
the contrary conception, that the secretion of milk is due to a
ferment elaborated in the placenta and transferred to the maternal
circulation at the time of birth. These theories are based mainly
on clinical evidence of a somewhat questionable value.

According to Miss Lane-Claypon and Starling's experiments, after
multiparous rabbits are injected with fcetal extract milk is secreted
by the glands. This result was explained as follows : " The multi-
parous rabbit differs from a virgin rabbit in possessing ready-formed
alveoli, i.e. secretory structures. On the theory which we have
adopted, the circulation of the mammary hormone should diminish
any secretion in these alveoli, and should cause growth. In all our
experiments at least twenty-four hours elapsed between each two
injections. It is probable that the hormone was rapidly absorbed
from the injection, and was therefore present in the blood of the
animal only for a certain fraction, say a few hours, out of the twenty-
four. While it was circulating it should cause building up of the
secreting cells. Directly, however, it ceased to circulate, the cells
would enter into dissimulative activity resulting in secretion. By
our injections, therefore, we are not able to imitate the continuous
stimulus of pregnancy. We are rather producing each day a
pregnancy of a few hours followed by a parturition. These factors
should therefore result in the production of milk in any animals
possessing the structures (i.e. the alveoli) which are capable of
secreting milk, and would therefore account for the secretion
of milk observed by us in all the cases where multiparous rabbits
were the objects of our experiment."

It has been shown that in the foetus itself there is an increased
growth of the mammary glands during the last part of pregnancy,
while it is well known that a secretion is often formed in the glands
of the newly born. Halban has explained this secretion as the
result of removal of the inhibitory influence — that is to say, it is due
to the same circumstance as the secretion in the mother. Miss
Lane-Claypon and Starling point out that the complete change
which occurs in the environment of the newly-born animal must
induce equally profound changes in the metabolism, and there is
consequently no difficulty about the conclusion that the formation
of the mammary hormone ceases with the commencement of extra-
uterine life.

The general conclusions at one time reached by these authors

1 He points out that in cases of abortion the secretion of milk may not
begin until some days after the death of the child. This he believes to be due
to the circumstance that the placenta remains alive during the interval.

2 Keiffer, " Recherches sur 1' Anatomic et la Physiologic de la Mamelle,"
Bull, de la Soc. Beige de Qyn. et d'Obstet., 1901-02.

614 THE PHYSIOLOGY OF REPRODUCTION

may be summarised as follows : The anabolic changes associated with
the growth of the mammary glands are due to the assimilatory effects
of a hormone elaborated in the foetus and carried thence through the
placenta by the foetal and maternal circulation. The removal of this
stimulus produces those katabolic changes which are involved in the
breaking down of the built-up tissues and the consequent formation
of milk.1

In criticism of these conclusions, which, however, the authors
never regarded as more than tentatively established, certain
objections were urged. It was pointed out that in certain animals
the period of lactation may continue for an almost indefinitely long
time, so that it would appear as if the katabolic processes involved
in milk-secretion were out of all proportion to the anabolic processes
concerned in the building up of the gland tissue. For example, it
is stated that in castrated cows the mammary glands may remain
perpetually active for years and years so long as milking is regularly
continued (see p. 600). Moreover, in some animals (e.g. mares) a
secretion of milk may be induced artificially as a result of a
mechanical stimulus set up by repeated attempts at milking. In
one instance known to the writer, a mare which had never had a foal
could be made to yield milk at any time for years. It would seem
probable, however, that in such cases there must have been an
original tendency to secrete, and that this tendency was merely
augmented by the emptying of the galactophorous ducts. This is in
accordance with the view that the emptying of the ducts during
normal suckling constitutes a physiological stimulus which acts on
the gland-cells, either directly or by means of a reflex.

Heape2 has pointed out as an objection to Starling's theory of
the foetal hormone that virgin bitches are frequently known to
produce milk, and that the quantity secreted may even be sufficient
to admit of their rearing pups. He also refers to a statement by
Tegetmeier and Sutherland 3 that mules may yield milk in sufficient
abundance to rear a foal. He concluded, therefore, that the source
of the stimulus which excites the development of the mammary
glands is to be sought in the ovary rather than in the foetus.

Instances have also been recorded by Knott 4 and others, in which
males have secreted milk, thus showing that mammary development is

1 According to Foa (loc. cit.) foetal extract has no inhibitory influence on
mammary secretion.

2 Heape, "The Source of the Stimulus which causes the Development of
the Mammary Gland and the Secretion of Milk," Proc. Phys. Soc., Jour, of
Physiol., vol. xxxiv., 1906.

3 Tegetmeier and Sutherland, Horses, Asses, Zebras, Mules, and Mule
Breeding, London, 1895.

4 Knott, "Abnormal Lactation, etc.," American Medicine, vol. ii., (new series,
June) 1907. Of. Wiedersheim (see p. 587).

LACTATION 615

not necessarily even a female function ; but such cases are at all events
exceedingly rare.1 Knott mentions cases in which suckling occurred
in a bull, a male goat, a wether, and in men. He also cites instances
of virgin girls who were nurses secreting copious supplies of milk as
a consequence of allowing infants to suck their nipples; and thus he
supports Heape's objection to the fetal hormone theory. Gellhorn 2
cites similar cases, including one o'f a virgin monkey (Cercopithecus).
Another case is mentioned of a woman who suckled children
uninterruptedly for forty- seven years, and in her eighty-first year
had a moderate but regular supply of milk,3 thus showing that
mammary secretion may continue exceptionally for long after the
menopause, and presumably, therefore, in the absence of any sort of
stimulus from the generative organs. This observation further
supports the idea referred to above, that normal suckling acts by
itself as a physiological stimulus for mammary secretion.

Halban4 has remarked that the seat of the stimulus for milk
secretion nrnst be placed outside the foetus, since parturition may
result not only in the mother secreting but also the foetus which
produces the so-called "witch's milk." Again, cases are described
in which a woman has produced a healthy, well developed child, and
yet secreted very little milk.5 O'Donoghue0 has pointed out that
the rabbit secretes milk several days before parturition, whereas
man and Dasyurus do not do so until several hours after it. More-
over, Hammond 7 has recorded a case of a goat which secreted large
amounts of milk (800 c.c. daily) for three weeks before parturition.

An equally forcible objection to the theory of the fo3tal hormone
is supplied by the Monotremata, which are the lowest order of
Mammalia. These animals are oviparous, the developing embryo
being contained in an egg, which does not enter into any sort of
connection with the uterine wall. Halban,8 however, has made the
suggestion, which is quoted by Miss Lane-Claypon and Starling, that
since the embryo goes on increasing in size during its passage down
the female generative tract, and since the shell of the egg is porous,

1 The occasional occurrence of milk secretion in the newly born, both males
and females, is well known.

2 Gellhorn, loc. cit.

3 Knott, loc. cit.

4 Halban, "Die innere Sekretion von Ovarium und Placenta," Arch. f. Gyn.,
vol. Ixxv., 1905.

5 Hammond, "On the Causes Eesponsible for the Developmental Progress
of the Mammary Glands in the Rabbit during the latter part of Pregnancy,"
Proc. Roy. Soc., B., vol. Ixxxix., 1917.

6 O'Donoghue, "The Growth Changes in the Mammary Apparatus of
Dasyurus and the relation of the Corpora Lutea thereto," (Juar. Jour. Micr.
Science, vol. Ivii., 1911.

7 Hammond, loc. cit.

8 Halban, loc. cit.

616 THE PHYSIOLOGY OF REPRODUCTION

it is not impossible that substances ma}7 diffuse outward from tbe
embryo and be absorbed by the uterine mucous membrane, and so be
carried into the maternal circulation.

Miss Lane-Claypon and Starling, however, never contended that
the foetus is the sole source of the stimulus for mammary develop-
ment. On the other hand, they specially mentioned that the growth
of the mammary glands which occurs at puberty, for instance, can
only be attributed to ovarian influence, since it does not take place
if the ovaries have been previously removed. It is not improbable,
therefore, that an ovarian stimulus is also responsible for producing
the growth of the glands in Monotremes, in just the same kind of
way as has been demonstrated for other animals.

The foetal hormone theory has now been superseded by the
hypothesis of the corpus luteum as the main controlling factor in
the growth of the mammary glands. Starling and Lane-Claypon,
however, did useful service in emphasising the part played by the
foetus in promoting the growth of the glands in pregnancy, for it is
only in the presence of the foetus in utero, at any rate in placental
Mammals, that the complete development of the glands followed by
full lactation is normally attained.

The Corpus Luteum. — Ancel and Bourn1 were the first to show
that the growth of the mammary glands during the first part of
pregnancy is due to the corpus luteum. Their researches were upon
the rabbit which only ovulates after copulation (see p. 129), so that
normally, since the discharged ova are fertilised, the presence of
corpora lutea is always associated with pregnancy. Ancel and Bouin,
however, by employing males in which the vasa deferentia had been
severed, were able to induce the formation of corpora lutea without
the occurrence of gestation. The same results can be brought about
by severing the Fallopian tubes of the female or by removing the
uterus, as was shown later by the present writer, working in
conjunction with Mr. Hammond.2 We described the condition
produced as one of "pseudo-pregnancy," a name already used by
Hill and O'Donoghue3 to designate the similar state of functional
correlation which occurs normally in the Marsupial cat (Dasyurus
vivemnm) after spontaneous ovulation. These authors have shown
that in Dasyurus the changes undergone by the mammary glands
are identical whether pregnancy supervenes or not (see p. 36).

1 Ancel and Bouin, see references, p. 371. For a full account of the changes
in the glands with many references to literature see Schil, Recherche* sur la
Cllande Mammaire, Nancy, 1912.

2 Hammond and Marshall, "The Functional Correlation between the
Ovaries, Uterus, and Mammary Glands in the Rabbit," Prof!. Roy. Soc., B.,
vol. Ixxxvii., 1914.

3 Hill and O'Donoghue, "The Reproductive Cycle in the Marsupial Cat,
Dasyurus viverrinm" Quar. Jour. Micr. Sci-ence, vol. lix., 1913.

LACTATION

617

There is always a hypertrophy followed by a secretion of milk, and
superficially it is impossible to distinguish pseudo-pregnancy from true
pregnancy. Moreover, in the dog,1 which also ovulates spontaneously,
pseudo-pregnancy may follow the discharge of the ova, the corpus
luteum persisting and the mammary glands undergoing growth
followed by secretion, a fact which explains the observations of

FIG. 168.— Photograph of mammary tissue of virgin rabbit. The mammary
development is limited to a few ducts. (From Hammond and Marshall.)

FIG. 169. — Photograph of mammary glands of pseuda-pregnant rabbit
fourteen days after oestrus. The rabbit had never bred. (From
Hammond and Marshall.)

Heape and others that even virgin bitches frequently lactate and are
capable of suckling litters of pups produced by other individuals.

The hypertrophy of the mammary glands in the pseudo-pregnant
rabbit culminates at about the sixteenth day, after which time it begins
to regress, but milk may be expressed from the nipples from the
nineteenth day onwards for a week or so, and even in individuals
which were previously virgins, while, as already mentioned, on

1 Marshall and Hainan, "On the Post-CEstrous Changes occurring in the
Generative Organs and Mammary Glands of the Non-Pregnant Dog," Proc. Roy.
Soc., B., .vol. Ixxxix., 1917.

2O A

6i8 THE PHYSIOLOGY OF REPRODUCTION

about the eighteenth day the rabbit may display the instincts
associated with parturition (see p. 576). In true pregnancy the milk
glands still continue to grow, increasing in thickness and in weight
until from the twenty-fourth to the thirtieth day, that is to say,
until at or near the time of parturition.1 The pseudo-pregnant
condition thus differs from that of true pregnancy. Similarly in
the pseudo-pregnant bitch the milk glands do not hypertrophy to
the same extent as in the pregnant animal. In both species of
Mammals the differences in mammary development are less marked
in individuals which have previously borne young and in which
consequently the mammary glands had already undergone a hyper-
trophy which was to a great extent persistent.

Ancel and Bouin 2 ascribe the growth of the milk glands in the
later part of pregnancy to the myometrial gland, which is stated to
consist of clumps of epithelioid cells lying under the placental cells
and between the muscle cells of the longitudinal and circular coats
in close proximity to the blood-vessels. They suggest that this
gland is an organ of internal secretion which takes over the functions
of the corpus luteum during the second half of pregnancy, controlling
the later or " glandular " phase of the mammary gland as well as the
tolerance of the uterus for the foetus. Fraenkel 3 has confirmed the
observations upon the presence of the myometrial gland in the rabbit
but has failed to find it in other species examined. Mercier,4
however, has identified the cells of the gland with certain phagocytic
cells which he had previously found in the pregnant uterus.
Hammond5 says that they are not constant even in rabbits, and
when present are probably foetal cells which have wandered into
the muscular coat.

As already mentioned, the placenta has also been suggested as a
source of the stimulus for the mammary growth of pregnancy.
Hammond, however, has eliminated this organ as a possible factor
by causing decidual tissue to form through the stimulation of the
uterus by a foreign body or by an incision after the manner of Loeb

1 Hammond, "On the Causes Responsible for the Developmental Progress
of the Mammary Glands in the Rabbit in the latter part of Pregnancy," Proc.
Roy. *S'oc., B., vol. Ixxxix., 1917.

2 Ancel and Bouin, "Sur 1'Existence d'un Glande Myometriale, etc.,"
C. R. Assoc. des Anat., 13 Reunion, 1911; "Recherches sur les Fonctions
du Corps jaune gestatif," Jour, de Phys. et de Path. Gen., vol. xiii., 1911 ;
" Sur 1'Evolution de la Glaride mammaire pendant la Gestation," C. R. de la
Soc. Jiiol., vol. Ixxii., 1912. See also C. R. de PA cad. des Sciences, vol. cliv., 1912.

3 Fraenkel, " Untersuchungen iiber die Sogenannte Glande endocrine
myom6triale," Arch.f. G'yn., vol. xcix., 1913.

4 Mercier, " Sur 1'Existence de Nephrophagocytes dans le Muscleuterin,
etc.," C. R. de la Soc. de Bi-ol., vol. Ixxii. ; and other papers in vols. Ixxiii. and
Ixxiv., 1912 and 1913.

5 Hammond, loc. rit.

LACTATION 619

(p. 374), and then finding that the development of the glands was
never in excess of what takes place under the influence of the
corpora lutea of pseudo-pregnancy. Moreover, he found that in
rabbits in which the foetuses were removed but the placentas
retained there were no secondary growth changes in the milk glands.
Biedl and Koenigstein1 had already shown that implantation of
placenta was without effect on the glands but that transplantation
of the foetus resulted in mammary growth and the secretion of
inilk.

Hammond found also that, contrary to the generally accepted
opinion, the corpus luteum in the rabbit is fully persistent and
therefore active during the second half of pregnancy. This con-
clusion is based on a series of measurements of corpora lutea at
different days after copulation in pregnant and pseudo-pregnant
individuals, and in others in which decidual cells had been experi-
mentally produced or in which the fetuses had been removed. It
was found that the corpora lutea, after the sixteenth day, retained
their size only in pregnant rabbits and in these underwent some
further development ; in the other three series they underwent a
very marked regression. Hammond concluded, therefore, that the
development of the mammary glands of the rabbit during the second
part of pregnancy is under the same influence as that which con-
trols it during the first half, namely, the corpus luteum, and that
the further development and persistence of the latter organ in the
last part of gestation is due to the presence of the foetus.

In the virgin rabbit, as already mentioned, the mammary tissue
before ovulation is limited to a few small ducts in the immediate
vicinity of the nipple, no true growth taking place until the corpus
luteum begins to develop. In polyoestrous animals which ovulate
spontaneously, on the other hand, notwithstanding the fact that
they do not experience pseudo-pregnancy (excepting possibly in a
very abbreviated form), mammary tissue may be built up even in
the virgin to such an extent that at a certain stage fluid secretion
occurs. This has been shown to be so by Woodman and Hammond 2
in the virgin heifer, in which mammary activity was found to take
place during the oestrous cycle. In such animals they found in the
udder the characteristic proteins (caseinogen, globulin, and albumen)
of colostrum, together with small amounts of fat, lactose, and
proteose.

The correlation between the generative organs and mammary
glands in the guinea-pig has been deal-t with in a series of papers

1 Biedl and Koenigstein, "Ueber das Mammahormon," Zeitsch. f. Exp. Path,
und T/ter., vol. viii., 1910.

2 Woodman and Hammond, " Note on the Composition of a Fluid obtained
from the Udders of Virgin Heifers," Jour, of Agric. Science, vol. xii., 1922.

620 THE PHYSIOLOGY OF REPRODUCTION

by Leo Loeb.1 He states that the presence of well-preserved corpora
lutea does not lead to proliferation in the mammary tissue until a
comparatively late stage of pregnancy (namely, after the twenty-
fourth day). He remarks that the guinea-pig appears to differ from
the rabbit in this respect, in that in the former animal the stimulus
has to accumulate for a considerable period before reaction sets in.
But in guinea-pigs castrated during pregnancy, and in which the
pregnancy continued, proliferative changes were absent in the
mammary gland. Complete extirpation of the corpora lutea similarly
prevents the active secondary proliferation of the glands which
occurs at a late stage.2 The rat differs from the guinea-pig in that
the corpus luteum persists for a considerable time during lactation,
and perhaps consequently ovulation and heat are inhibited during
the nursing period of the rat, while in the guinea-pig they continue
to take place. The effects of castration on the lactating glands of
the rat and guinea-pig are not noticeable until suckling ceases, when
involution sets in. With regard to the nature of the stimulus calling
forth lactation Loeb says it is neither purely functional nor purely
formative but intermediate between the two.3

Steinach's experiments in which he transplanted ovaries into
previously castrated guinea-pigs or rats are referred to elsewhere
(see p. 346). He concludes that all the influence exercised by
the ovary on the mammary glands is due to the interstitial or
puberty gland, which promotes mammary growth and secretion.
Athias4 has described similar experiments on guinea-pigs, and, as
a result of studying the histology of the transplanted ovaries, is
of opinion that the development of the mammary glands and the
initiation of milk secretion depend upon hypertrophied theca cells
or ripe follicles. Both these investigators, therefore, contrary to
the views of Ancel and Bouin and others, conclude that the presence
of corpora lutea is unnecessary for the development of the mammary

1 Loeb and Hesselberg, " The Cyclic Changes in the Mammary Gland, etc.,"
Jour. Exp. Med., vol. xxv., 1917; Loeb and Kuramitsu, "The Influence of
Lactation," " The Involution of the Uterus, etc.," and " The Effect of Suckling,"
Amer. Jour. Physiol., vols. Iv. and Ivi., 1921 ; and Loeb, "The Relation of the
Ovary to the Uterus and Mammary Gland," Trans. Amer. Gyn. Soc., 1917.

2 Extirpation of corpora lutea in the guinea-pig, according to this author,
accelerates ovulation and heat and the associated primary proliferation of the
mammary gland.

3 A functional stimulus is one leading to activity unaccompanied by growth ;
a formative stimulus leads to a multiplication of cells and nuclei, i.e. to growth
generally and to differentiation (Virchow). In the mammary gland secretion
is accompanied by amitotic nuclear division. Mitotic proliferation precedes
and follows secretion, but is not associated with actual secretion.

4 Athias, " L'Activite Secretaire de la Glande Mammaire Hyperplasiee,"
C. R. de la Soc. de Biol., vol. Ixxviii., 1915 ; " Etude Histologique d'Ovaires
Greffes," and " Sur le Determinisme de 1'Hyperplasie," C. R. de la Soc. de Biol.,
vol. Ixxix., 1916.

LACTATION 621

glands. It would seem possible that the guinea-pig may differ from
the rabbit in this respect, or more probably that under certain
conditions glandular elements in the ovary, other than corpora
lutea, may take over the function of the latter organs. In this
connection it may be recalled that according to Loeb the primary
growth of the mammary glands takes place before ovulation, and
the main or secondary growth is postponed until a later phase
when the corpora lutea have been in existence for some time.

It has been shown that extract of corpus luteum has a marked
galactogogue effect, intravenous injection resulting in an immediate
outpouring of milk. This was first demonstrated by Ott and Scott l
in the goat and has since been confirmed for man and other animals
by Sharpey Schafer,2 and Mackenzie,3 and Gavin.4 Ott and Scott were
the first to show also that extract of posterior lobe of pituitary gland
had an even more marked result. Extracts of placenta, involuting
uterus, and pineal gland were similar, as well as the lactating gland
itself. According to Hammond5 the pituitary and other extracts
probably act directly on the gland-cells, and it seems certain that
more milk may be drawn off than could have been present in the
sinuses and ducts at the moment of injection. The extract, there-
fore, must cause the glands to secrete. Sharpey Schafer,6 however,
is of opinion that the hormone acts on the unstriated muscle cells
in much the same kind of way as extract of pituitary or corpus
luteum causes contraction of the muscle of the uterus. Sharpey
Schafer states further that the ovary appears to secrete two
excitants, one increasing the contractility of muscle, the other
inhibiting it.

Simpson and Hill,7 however, differ from Sharpey Schafer and
point out that barium chloride, which is a specific stimulus for
muscle, has no effect on the milk fiow.

It is probable, therefore, that the corpus luteum is normally an

1 Ott and Scott, "The Galactogogue Action of the Thymus and Corpus
Luteum," Proc. Soc. Exp. Biol. and Med., vol. viii., 1910. See also Ott's
Contributions to Physiology, Part xix., 1912.

2 Schafer and Mackenzie, " The Action of Animal Extracts on Milk Secre-
tion," Proc. Roy. Soc., B., vol. Ixxxiv., 1911.

3 Mackenzie (K.), " An Experimental Investigation of the Mechanism of Milk
Secretion," Qiiar. Jour. Exp. Physiol., vol. iv., 1911. Hill and Simpson,
" The Effect of Pituitary Extract on Milk Secretion in the Goat," Quar. Jour.
Exp. Biol., vol. viii., 1914. See also Ainer. Jour, of Physiol., vol. xxxv., 1914,
and Proc. Soc. Exp. Biol. and Med., vol. xi., 1914.

4 Gavin, " On the Effects of Administration of Extracts of Pituitary Body
and Corpus Luteum to Milch Cows," Quar. Jour. Ex.p. Physiol., vol. vi., 1913.

5 Hammond, " The Effect of Pituitary Extract on the Secretion of Milk,"
Quar. Jour. Exp. Physiol., vol. vi., 1913.

6 Sharpey Schafer, The Endocrine Organs, London.

7 Simpson (S.) and Hill, "The Mode of Action of Pituitary Extract," Quar.
Jour. Exp. Physiol., vol. viii., 1915. See also Schafer's Note to this paper.

622 THE PHYSIOLOGY OF REPRODUCTION

essential factor in both mammary growth and the initiation of
mammary secretion, and no contradiction is involved in the assump-
tion that the hormone or hormones when gradually secreted into the
circulating blood in a state of nature act differently from the sudden
injection of a considerable quantity of the substances. It is possible
also that the hprmone which has the power of increasing muscular
contractility is produced in greater abundance at about the time
of parturition (see p. 577).

It has been already shown that after ovariotomy lactation may
be prolonged for an almost indefinite period, and further, that after
the same operation the pituitary gland undergoes hypertrophy. It
is not unlikely that these two facts are correlated, and that after the
removal of the ovaries the function of the corpus luteum in relation
to milk secretion may be taken over vicariously by the pituitary,
which, unlike the luteal gland, does not atrophy after a comparatively
short period. Such a conclusion, however, is at the best a very
tentative one, for although the corpus luteum in Dasyurus l and the
rat z is said to persist during lactation, it is not known how long the
organ continues to function in other Mammals.3 Relatively to
the duration of suckling the corpus luteum in most species probably
persists for only a short time.

1 Sandes, " Tlie Corpus Luteum of Dcuyurus" Proc. Linn. Soc. N.S. W.,
vol. xxviii., 1903.

2 Watson (B. P.), "On the State of the Ovaries during Lactation," Proc.
Phi/s. 8oc., Jour, of Physiol., vol. xxxiv., 1906.

3 The part of the pituitary which hypertrophies after ovariotomy is said to
be the anterior lobe, while the part that elaborates the galactogogue is the
posterior lobe. The hypothesis suggested above, therefore, assumes a functional
relation between the two lobes of which there is some evidence.

CHAPTEK XIV
FERTILITY

" Nam multum harmonise veneris differre videntur.
Atque alias alii complent magis ex aliisque,
Succipiunt alise pondus magis inque gravescunt.

Atque in eo refert quo victu vita colatur."

— LUCRETIUS.

THE rate of propagation in any species of animal depends not only
upon the average number of young born in each litter, but also upon
the frequency of recurrence of the sexual season and the duration
of the reproductive period in the animal's life. The frequency of
recurrence of the sexual season — that is to say, the cestrous cycle — in
different species of Mammals has been discussed at some length in an
early chapter of this work. In the present chapter it remains to
consider a little more closely some of the causes which control this
periodicity and the factors which affect fertility.

The duration of the reproductive period of an animal's existence
extends in most cases from a time when that animal has almost
reached its full size until the beginning of senescence, so that the
normal period of generative activity in the individuals of any given
species bears a definite relation to their average length of life. In
the male the sexual maturity is usually reached later than in the
female. Moreover, in the male there is no definite ending of the
reproductive period, since in man, for example, the power of producing
spermatozoa continues in a gradually diminishing degree even in
extreme old age, whereas in the female, on the other hand, the
climacteric marks the cessation of generative activity (see .below,
p.714)/

Broadly speaking, the average number of young produced in a
litter in any species of Mammal is inversely proportional to the
average size of the animals belonging to that species. Thus, in most
species of Ungulates twins are the exception rather than the rule ;
and there are seldom more than two young produced at a time even
in sheep and goats, which show a greater degree of fertility than
most Ungulates. The sow, however, is exceptional in having very
large litters, as many as seventeen young being sometimes born.
On the other hand, in small Mammals such as Eodents large litters

623

624 THE PHYSIOLOGY OF REPRODUCTION

are the rule ; the rat, for example, being known occasionally to bear
as many as sixteen or even twenty young ; but the Cheiroptera, or
bats, are remarkable for their relative infertility, only one young one
ordinarily being produced at a time, although the common bat is no
larger than the mouse.

Generally speaking, only one young one is produced in those
animals in which the period of gestation exceeds six months. The
number of teats characteristic of the species also affords an approximate
indication of the average size of the litter.

" Among women, the birth of twins occurs once in about eighty
deliveries. Triplets, quadruplets, quintuplets, and even higher
figures, are occasionally observed ; they are very uncommon, and
the rarity is progressive with the number. The normal or ordinary
rule in woman is to bear one child at a time ; and the next most
frequent condition is temporary or persistent sterility — two points in
which she signally differs from what is generally believed [of
animals]." 1 Veit's statistics 2 for 13,000,000 births in Prussia showed
that twins were produced once in 89 cases, triplets once in 7910, and
quadruplets only once in 371,125 cases. There is some evidence also
that the frequency of occurrence of multiple pregnancy in women
depends upon the race or climate, and that it is commoner in cold
than in warm countries.3

Herbert Spencer 4 elaborated a theory whereby he explained the
relative degrees of fertility in the different races of men and animals.
According to this theory the power to sustain individual life and
the power to produce new individuals are inversely proportional, a
conclusion which is summarised in the generalisation that Individua-
tion and Genesis vary inversely. When there is an abundant food
supply and a favourable environment, and the necessary expenditure
of energy is relatively slight, the cost of Individuation is much
reduced, and the rate of Genesis is correspondingly increased ; in
other words, there is a high degree of fertility. Spencer cited
the Boers, the Kaffirs, and the French Canadians as examples of
fertile races in which the rate of increase is associated with a nutrition
that is greatly in excess of the expenditure. Conversely, he concluded
that a relative increase of expenditure leaving a diminished surplus
reduces the degree of fertility, and in support of this statement
adduced evidence that bodily labour tends to make women less

1 Matthews Duncan, Fecundity, Fertility, Sterility, and Allied Topics,
Edinburgh, 1866.

2 Veit, " Beitrage zur geburtshulflichen Statistik," Monatsschr. f. Geb., vol. vi.,
1855.

3 For further statistics and references see Williams, Obstetrics, New York,
1904.

4 Spencer, Principles of Biology, Revised Edition, vol. ii., London, 1899.

FERTILITY 625

prolific, since the reproductive age is said to be reached a year later
by women of the labouring class than by middle-class women.

Spencer applied his generalisation to animals as well as to man,
and attempted to explain thereby the average contrast between the
fertility of birds and Mammals. " Comparing the large with the
large and the small with the small, we see that creatures which
continually go through the muscular exertion of sustaining them-
selves in the air and propelling themselves rapidly through it, are
less prolific than creatures of equal weights which go through the
smaller exertion of moving about over solid surfaces. Predatory
birds have fewer young ones than predatory Mammals of approximately
the same sizes. If we compare rooks with rats, or finches with mice,
we find like differences. And these differences are greater than at
first appears. For whereas among Mammals a mother is able,
unaided, to bear and suckle and rear half-way to maturity a brood
that probably weighs more in proportion than does the brood of a
bird ; a bird, or at least a bird that flies much, is unable to do this.
Both parents have to help ; and this indicates that the margin for
reproduction in each adult individual is smaller."

Spencer cites numerous instances from among both birds and
Mammals illustrating the effects of different degrees of activity upon
fertility. The hare and the rabbit, for example, are closely allied
species, "similar in their diet, but unlike in their expenditures for
locomotion. The relatively inert rabbit has six young ones in a litter,
and four litters a year; while the relatively active hare has but
two to five in a litter. That is not all. The rabbit begins to breed
at six months old ; but a year elapses before the hare begins to breed.
These two factors compounded result in a difference of fertility far
greater than can be ascribed to unlikeness of the two creatures
in size."

Furthermore, Spencer refers to the case of the bat, which has
been already mentioned as being abnormally unprolific in proportion
to its size. The relatively low rate of multiplication is of course
ascribed to a relatively high rate of expenditure resulting from the
habit of flying.

In a similar way Spencer explains such well-known facts as that
hens cease to lay when they begin to moult. " While they are
expending so much in producing new clothing, they have nothing to
expend for producing eggs."

There can be little doubt that Spencer's generalisation is in the
main true, but it is equally certain that it cannot be applied
indiscriminately to explain the relative degrees of fertility in all
animals, and consequently it must not be pressed too far. Some of
the more special factors which control fertility are referred to below,

626 THE PHYSIOLOGY OF REPRODUCTION

and it is evident that many (though not all) of these fall within the
scope of Spencer's generalisation.

The rate of increase as distinguished from the rate of reproduction
(in any given species) depends upon a large number of factors, of
which the rate of reproduction is only one.

EFFECT OF AGE

Matthews Duncan1 has discussed at some length the variation
which occurs in the fertility of women according to their age. He
adduces statistical evidence showing that the fertility of the female
population increases gradually from the commencement of the child-
bearing period of life until about the age of thirty, and then it
gradually declines. He shows also that the fertility is much greater
before the climax is reached (at thirty years) than after it is passed.
These conclusions, however, apply merely to the actual productiveness
(i.e. the number of births), as opposed to the capability of bearing
children, which Duncan designates the fecundity. By eliminating
from his calculations all women not living in married life, Duncan
arrives at the following conclusions, which are based on statistics
showing the productiveness of wives : 2 (1) " That the initial fecundity
of women gradually waxes to a climax, and then gradually wanes " ;
(2) " That initial fecundity is very high from twenty to thirty-four
years of age"; and (3) "That the climax of initial fecundity is
probably about the age of twenty-five years." The fecundity of the
average individual woman may be described, therefore, as forming
a wave which, starting from sterility, rises somewhat rapidly to its
highest point, and then gradually falls again to sterility.

Pearl 3 refers to the case of a ewe whose complete breeding record
conforms to this description very closely. In her first two years she
had single lambs, in her third year twins, then for six years in
succession triplets, for the next six years twins, and finally for two
more seasons single lambs. In the next two years which were the
last of her life this ewe did not produce any lambs.

There can be no doubt that the majority of animals tend to
follow a similar law. A dog generally has fewer puppies in its first
litters than afterwards, while in its declining years there is a
diminution until sterility is reached once more. The same is said to
be the case with the bear, the elk, and other animals,4 but there are

1 Duncan, loc. cit.

2 It is, of course, obvious that it is impossible to determine statistically the
real " fecundity " (using the term as denned by Duncan) in view especially of
the practice of volitional interference with conception (see below, p. 659).

3 Pearl, "Note Regarding the Relation of Age to Fecundity," Science,
vol. xxxvii., 1913.

4 Duncan, loc. cit.

FERTILITY

627

obviously many individual exceptions. Minot1 observed that in
guinea-pigs the size of the litters increased with age during the first
sixteen months of their lives ; Hammond,2 on the authority of the
late Major P. G. Bailey, makes a similar statement for the rabbit ;
and Jones and Rouse,3 who give a review of the literature, besides
recording their own observations on various domestic animals, show
that a similar general rule holds good for cattle, sheep, and pigs.
Furthermore, King4 found that rats reach the height of their
reproductive capacity at about seven months, and that this age
represents also the median point in the animal's breeding career.

Geyelin5 gives the following table showing the fertility of the
domestic fowl at different ages : —

Sixth year after hatching
Seventh „ „

Eighth
Ninth

50 to 60

35 „ 40

15 „ 20

1 „ 10

First year after hatching - 15 to 20

Second „ „ 100 „ 120

Third „ „ - 120 „ 135

Fourth „ „ - 100 „ 115

Fifth „ „ - 60 „ 80

Pearl,6 however, states that the greatest egg production is in
the first year. With Barred Plymouth Rocks he found that repro-
ductive ability diminished with advancing age, being at its maximum
at ten to fourteen months. Robinson,7 writing of fowls and ducks,
says that few birds are as good breeders the third year as the
second, and fewer still are good after the third year. "It is largely
a question of condition ; the older a bird grows, the more difficult it
is to keep in good breeding condition."

EFFECTS OF ENVIRONMENT AND NUTRITION

That the generative system in animals is peculiarly susceptible to
changed conditions of existence has been recognised from early days.
Thus Aristotle 8 commented on the increased fertility of sheep in a
favourable environment. In more recent times Buffon,9 among
others, remarked on the fact that domestic animals breed oftener

1 Minot, "Senescence and Rejuvenation," Amer. Jour, of Physiol., vol. xii.,
1891.

2 Hammond, " On some Factors controlling Fertility in Domestic Animals,"
Jour, of Agric. Science, vol. vi., 1914.

3 Jones and Rouse, " The Relation of Age of Dam to observed Fecundity,"
Jour, of Dairy Science, vol. iii., 1920. See also article by Harrison, Amer.
Naturalist, vol. 1., 1916.

4 King, "The Relation of Age to Fertility in the Rat," Anat. Record, vol. xi.,
1916.

6 Geyelin, Poidtry-Breeding in a Commercial Point of View, London, 1865.

6 Pearl, "The Mode of Inheritance of Fecundity in the Domestic Fowl,"
Jour. Exp. Zool., vol. xiii., 1912 ; " Studies in the Physiology of Reproduction
in the Domestic Fowl," XVII., Genetics, vol. ii., 1917.

7 Robinson (J. H.), Principles and Practice of Poultry Culture, Boston, 1912.

8 Aristotle, History of Animals, Bohn's Library, London.

9 Buffon, Histoire Naturelle, Paris, 1802.

628 THE PHYSIOLOGY OF REPRODUCTION

and produce larger litters of young than wild animals belonging to
the same species; and Darwin, who made the same observation,
attributed the increased fertility of the former to a long habituation
to a regular and copious food supply without the labour of seeking
for it. " It is notorious how frequently cats and dogs breed, and
how many young they produce at birth. The wild rabbit is said to
breed four times yearly, and to produce each time at most six young ;
the tame rabbit breeds six or seven times yearly, producing each
time from four to eleven young. . . . The ferret, though so closely
confined, is more prolific than its supposed wild prototype [the
polecat]. The wild sow is remarkably prolific; she often breeds
twice in the year, and bears from four to eight, and sometimes even
twelve, young; but the domestic sow regularly breeds twice a year,
and would breed oftener if permitted ; and a sow that produces less
than eight at birth ' is worth little, and the sooner she is fattened for
the butcher the better.' The amount of food affects the fertility of
the same individual ; thus sheep which on mountains never produce
more than one lamb at birth, when brought down to lowland
pastures frequently bear twins. The difference apparently is not
due to the cold of the higher land, for sheep and other domestic
animals are said to be extremely prolific in Lapland." l

Darwin remarks that birds afford still better evidence of increased
fertility resulting from domestication. Thus, in its natural state
the female of Gallus bankiva, the wild representative of the common
fowl, lays only from six to ten eggs ; the wild duck lays from five
to ten eggs, as compared with eighty or a hundred produced by
the domestic duck in the course of the year. Similarly, the turkey,
the goose, and the pigeon are more fertile in the domestic state,
though this is not the case with the pea-fowl. Among plants also
there are countless instances of increased fertility as a consequence
of cultivation.2

On the other hand, it is well known that wild animals, when
removed from their natural conditions and brought into captivity,
often become partly or completely sterile. Darwin discusses this
phenomenon at some length, and cites numerous cases from different
groups of animals and birds.

The Indian elephant, for example, seldom breeds in captivity,
although kept in a perfectly healthy condition and in its native
country. On the other hand, most members of the Suidae are
known to breed in menageries and zoological gardens, while many

1 Darwin, The Variation of Animals and Plants under Domestication, Popular
Edition, vol. ii., London, 1905.

2 Cf. also Spencer (loc. cit.), who discusses this question at some length in
connection with his generalisation that Individuation and Genesis vary inversely.
See above, p. 624.

FERTILITY 629

Ruminants breed readily in climates widely different from their
own. Carnivorous animals breed somewbat less freely in confine-
ment, and show considerable variation in different places. The
Canidre tend to be more fertile than the Felidse, while the members
of the bear group breed less easily. Rodents as a general rule fail
to breed after being brought into captivity, but there are several
exceptions. Monkeys also when kept in confinement only rarely
have young ones. Many of these animals, however, although failing
to conceive, are known to copulate freely. This is especially the
case with captive bears and monkeys, in which the typical phenomena
of prooestrum and oestrus occur. It would seem probable that the
sterility under these circumstances results from a failure to ovulate,
due possibly to an absence of ripe follicles in the ovaries.

Among birds, members of the hawk group very seldom breed in
captivity. The graminivorous birds show considerable variation,
some, like the canary, breeding freely in aviaries (although it was
some time before it became fully fertile), while others, like the
finches, only occasionally reproduce their kind when kept in
confinement. Gallinaceous' birds, on the other hand, show an
unusual capacity to breed in captivity, and the same is the case with
pigeons, ducks, and geese. Certain kinds of gulls also are known to
breed readily when kept in open spaces in zoological gardens.

As pointed out by Darwin, there is other evidence that changed
conditions of life may induce a disturbance of the sexual functions.
Thus when conception does occur under confinement, the offspring
are sometimes born dead or ill-formed, or otherwise show signs of
insufficiency of nourishment. The mother's milk may fail, indicating
an interference with those factors which control the mammary
metabolism. Moreover, in animals which are characterised by a
periodic growth of the secondary sexual characters, these sometimes
fail to make their appearance. The male linnet in captivity does
not assume its characteristic crimson breast, or the male bunting
(Eriiberizu passerina) the black colour on its head. Other birds, such
as a pyrrhula and an oriole, may acquire the appearance of the
hen, while a falcon (Falco albidus) has been observed to lose its adult
plumage.1 These facts seem to show that the generative metabolism
may be so altered by changed conditions of existence as to induce
not merely a state of sterility, but also an interference with the
secretory activity of the essential organs of reproduction.2

Darwin says : " We feel at first naturally inclined to attribute
[such results] to loss of health, or at least to loss of vigour ; but this

1 Darwin, loc. cit.

2 The relation between the gonads and the secondary sexual characters, and
the apparent dependence of the latter upon the secretory activity of the former,
are discussed in Chapter IX.

630 THE PHYSIOLOGY OF REPRODUCTION

view can hardly be admitted when we reflect how healthy, long-
lived, and vigorous many animals are under captivity, such as
parrots, and hawks when used for hawking, chetahs when used for
hunting, and elephants. The reproductive organs themselves are
not diseased;1 and the diseases from which animals in menageries
usually perish are not those which in any way affect their fertility.
The failure of animals to breed under confinement has been some-
times attributed exclusively to a failure in their sexual instincts.
This may occasionally come into play, but there is no obvious reason
why this instinct should be especially liable to be affected with
perfectly tamed animals, except, indeed, indirectly through the
reproductive system itself being ' disturbed. Moreover, numerous
cases have been given of animals which couple freely under
confinement, but never conceive; or, if they conceive and produce
young, these are fewer in number than is natural to the species. . . .
Change of climate cannot be the cause of the loss of fertility, for
whilst many animals imported into Europe from extremely different
climates breed freely, many others when confined in their native
land are sterile. Change of food cannot be the chief cause; for
ostriches, ducks, and many other animals, which must have under-
gone a great change in this respect, breed freely. Carnivorous birds
when confined are extremely sterile, whilst most carnivorous
Mammals, except plantigrades, are moderately fertile. Nor can the
amount of food be the cause ; for a sufficient supply will certainly be
given to valuable animals ; and there is no reason to suppose that
much more food would be given to them than to our choice domestic
productions which retain their full fertility. Lastly, we may infer
from the case of the elephant, chetah, various hawks, and of many
animals which are allowed to lead an almost free life in their native
land, that want of exercise is not the sole cause." Darwin shows
also that close confinement by itself does not necessarily cause
sterility, since such animals as the rabbit and ferret breed freely in
cramped hutches. The general conclusion reached is that "any
change in the habits of life, whatever these habits may be, if great
enough, tends to affect in an inexplicable manner the powers of
reproduction. The result depends more on the constitution of the
species than on the nature of the change ; for certain whole groups
are affected more than others ; but exceptions always occur, for some
species in the most fertile groups refuse to breed, and some in the
most sterile groups breed freely."

In support of these conclusions Darwin shows further that

1 Few observations have been made upon the condition of the gonads in
animals in captivity, but Branca ("Recherches sur le Testicule et les Voies
spermatiques dans Lemuriens en captivite," Jour, de V*Anat. et la Phys., vol. xl.,
1904) states that in captive lemurs he could find no spermatozoa in the testicles.

FERTILITY 631

domesticated animals also under new conditions occasionally show
signs of lessened fertility, and that animals such as the canary,
which now breed readily in a state of captivity, were formerly often
sterile.

Bles's observations,1 to which reference has already been made
(p. 18), seem to have a bearing on this question. This observer,
who has kept various kinds of Amphibia in captivity, has shown
that axolotls can only be induced to breed under certain special
environmental conditions. By feeding them copiously in summer
and allowing them to hibernate in winter, and then suddenly
transferring them to an aquarium stocked with growing plants and
provided with running water, these animals could be induced to
spawn within a few days. (Of. also Annandale's observations referred
to on p. 20.) Bles draws the conclusion that the difficulty so often
experienced in inducing Amphibians to breed in a state of captivity
is not due to toxic influence on the gonads resulting from the
confinement, but must rather be ascribed to the absence of the
necessary external stimuli without which the generative organs of
animals are incapable of properly discharging their functions. Bles
suggests that this view may help to explain why some animals (e.g.
insects) make their appearance in great numbers in one year, and
are comparatively scarce in another.

In animals whicli as a general rule breed freely in a state of
domestication or under confinement, it is probable that nutrition
plays the chief part (though by no means the sole part) in regulating
the capacity to produce offspring. That an insufficient or markedly
abnormal diet must affect this power is almost self-evident, and
Chalmers Watson 2 has shown that sterility is a common condition
among caged rats when fed exclusively upon meat.3 It is also
certain that an excessive quantity of nutriment is likewise prejudicial
to the proper discharge of the reproductive functions. No better
example could be given of the way in which overfeeding results in
a condition of sterility than that of the barren Shire mares, which
in some past years have been a striking feature at agricultural' shows
in England. Some foods are said to induce sterility more easily
than others. Sugar, molasses, and linseed are noted for having this
effect when given to cattle, but they are often used to prepare beasts
for show or sale, since they produce a good coat of hair and cause a

1 Bles, " The Life-History of Xenopus Icevis" Trans. Roy. Soc. Edin., vol. xli.,
1906.

2 Campbell and Watson, " The Minute Structure of the Uterus of the Rat,
etc.," Proc. Phys. Soc.., Jour, of Physiol., vol. xxxiv., 1906.

3 Cf. Pezard on "alimentary castration" as a result of a meat diet in fowls
(see above, p. 334). Moreover, Allen has shown that a deficiency of water-
soluble vitamins in the diet given to rats causes atrophy of the seminiferous
tubules of the testis (Anat. Record, vol. xvi., 1919).

632 THE PHYSIOLOGY OF REPRODUCTION

deposit of fat. Very fat animals do not come in season so often,
and consequently cattle " settle better and feed faster as they become
what the butchers designate ' fat ripe.' " In such animals there
can be no doubt that the ovarian metabolism is abnormal, and the
author has often found large quantities of bright orange-coloured
lipochrome in the interstitial tissue of the ovaries of fat cows and
heifers.1 Kirkham z records sterility in white and yellow mice which
after four to six litters lay down extensive quantities of fat and
thenceforward fail to breed. In man also obesity is known to be a
cause of sterility, in the male spermatogenesis being partly inhibited.3

A low condition, especially if associated with exposure to wet and
cold, as in the case of cattle wintered in the open air, or of cows
which have suckled a large calf or more than one calf, is also a
common cause of temporary barrenness.4 Certain other more special
causes of sterility are referred to briefly below (p. 644).

A few years ago the Koyal Agricultural Society of England
instituted an inquiry into the subject of fertility in sheep. The
investigation was conducted by Heape, at whose instigation it was
carried out. In the report/ which was subsequently published a
comparative account is given of the fertility of various breeds of
sheep chiefly in the South of England in the season 1899. The most
fertile breed was the Wensleydale, in which six flocks, consisting of
a total of 319 ewes, produced a percentage of 177'43 lambs. The
effects of locality are discussed, and there is an accumulation of
evidence indicating that the character of the district is not without
influence on the fertility of the breed. Thus, Lincoln sheep run on
the wolds, Shropshire sheep on a subsoil of New Red Sandstone, and
Hampshire sheep, which are not run upon chalk downs, are shown
to be associated statistically with a relatively high percentage of
infertility. The report shows further that the fertility of a flock
depends greatly upon its management, that the quality and quantity
of the food supplied affect the condition of the sheep, and so influence
their power to breed, that some seasons are more favourable to
fertility than others, and that sheep-stained pasture (or pasture
on which sheep have run for some considerable time previously)
is detrimental to breeding stock.

1 Marshall and Peel, "Fatness as a Cause of Sterility," Jour, of Agric. Science,
vol. iii., 1910. The lipochrome may have belonged to persistent corpora lutea.

2 Kirkham, "The Life of the White Mouse," Proc. Soc. Exp. Biol. and Med.,
vol. xvii., 1920.

3 Cooper, The Sexual Disabilities of Man, London, 1918.

4 Wallace (R.), Farm Live Stock of Great Britain, 4th Edition, Edinburgh,
1907.

5 Heape, "Abortion, Barrenness, and Fertility in Sheep," Jour. Roy. Ayric.
Soc., vol. x., 1899. See also Heape, " Note on the Fertility of Different Breeds
of Sheep, etc.," Proc. Roy. Soc., vol. Ixiv., 1899.

FERTILITY 633

The present writer has shown1 that in Scotch Blackfaced,
Cheviot, and other Scottish sheep the normal percentage of ova
discharged at any single oestrous period is not appreciably in excess
of the usual percentage of births at the lambing season. It would
seem probable, therefore, that a scarcity of twin births at lambing
time is the direct consequence of an abnormally low number of ripe
follicles in the ovary at tupping time (i.e. during the sexual season).
A low percentage of twins is generally associated with barrenness, a
fact which is recognised by flockmasters, and which is proved very
clearly by Heape's statistics. And since ewes which are con-
stitutionally barren are a rarity, there can be little doubt that
infertility among sheep is due ordinarily to an absence or great
scarcity of follicles available for ovulation at tupping time.

Scarcity of mature follicles must itself result either from a
retardation in follicular development or from an unusual tendency
towards follicular degeneration whether occurring shortly before the
sexual season or at some previous period in the animal's lifetime.
Atretic or degenerate follicles are by no means uncommon in sheeps'
ovaries, the process of atresia appearing to set in most commonly in
follicles which have readied a size varying from about one-eighth
to one-half the dimensions of the mature follicle. It may set in,
however, at practically any stage of development and probably in
the so-called primordial follicle (see p. 151). There can be little
doubt that an excessive follicular degeneration results usually from
an insufficiency of stimulating power at the disposal of the ewe.

That a relative scarcity of ripe follicles in sheeps' ovaries at the
sexual season is due to retardation of development is a conclusion
which is based on inference rather than observation, for little is
known regarding the actual rate of growth of the Graatian follicle.
Nevertheless, there is every reason for supposing that the processes
of growth and maturation can lie very largely influenced both by
insufficiency of food supply on the one hand and by artificial
stimulation on the other, as has been shown for other animals.
This fact has been recognised for years past by certain individual
flockmasters who have consistently practised the methods of
" flushing " or artificially stimulating their ewes by means of an
extra supply of special food at the approach of the tupping season,
but no precise records of the effects of this process had been
published until lately, when the Highland and Agricultural Society
of Scotland undertook an investigation upon this subject.

In the report which has since been issued,2 and which contains

1 Marshall, " The (Estrous Cycle and the Formation of the Corpus Luteum
in the Sheep," Phil. Trans., B., vol. cxcvi., 1903.

2 Marshall, " Fertility in Scottish Sheep," Trans. Highland and Agric. Soc.,
vol. xx., 1908. See also Proc. Roy. Soc., B., vol. Ixxvii., 1905.

634 THE PHYSIOLOGY OF REPRODUCTION

the lambing statistics for various flocks of Scottish sheep for the
years 1905, 1906, and 1907, it is shown that the percentage of
lambs born was, as a general rule, highest among sheep which had
been subjected to a process of artificial stimulation. The method
adopted was to feed the ewes upon turnips, oats, maize, dried grains,
or other additional food at the tupping time and for about three
weeks previously, while maintaining them upon grass only during
the greater part of the year. Some flocks, however, received a
limited supply of extra food (generally turnips) during gestation,
and especially during the later part of this period. The additional
supply of turnips, which are specially rich in carbohydrate material,
was found to be in no way detrimental to fertility, but rather the
reverse, when accompanied by other food (pasture), and so not taken
in excess. The statistics show that in the flocks treated in the way
described, the percentage of lambs per ewes l was almost invariably
in excess of the average percentage for flocks which received no
special treatment, while the percentage of barren ewes was usually
also less in the specially fed flocks. In some cases the number of
lambs per ewes in the flushed flocks was nearly 200 per cent.
Among flocks belonging to the same breeds (Border Leicester or
half-bred Border Leicester) which received no sort of special
treatment, the average proportion of lambs per ewes was between
150 and 160 per cent., while flocks which were run upon superior
pasture at the approach of the sexual season, without being otherwise
specially fed, generally produced a slightly larger percentage of
lambs. The twins appear almost invariably to have been born early
during lambing, thus showing that the generative activity of the
ewes tends to be greatest at the commencement of the sexual season.
It has proved more difficult to obtain definite information
concerning the effects of flushing in one year upon the fertility of
the ewes in subsequent seasons. The more usual experience of
flockmasters seems to be that flushing is not in any way prejudicial
to breeding stock unless it is overdone, the object of the process
being to get the animals in an improving condition without
permitting them to put on too much fat. If the artificial feeding
is excessive and the sheep are forced to depend for the remainder
of the year upon a mere sustenance diet, it is easy to understand
that they would tend to deteriorate, and their subsequent fertility
become impaired, owing probably to a higher frequency of follicular
degeneration. It is seemingly for such a reason that some flock-
masters regard the practice of flushing as one altogether to be
deprecated. There is some evidence, however, that if sheep are
specially fed in one season, the process must be repeated in the next,

1 That is to say, the number of lambs per 100 ewes.

FERTILITY 635

and that if this is omitted the sheep tend to be less fertile than if
they had never been subjected to flushing.

It has already been mentioned (p. 364) that the practice of
flushing tends to hasten the sexual season, the sheep coming "on
heat" sooner than they would otherwise. The result must be
ascribed to a general increase in the ovarian metabolism consequent
upon the stimulating power of the special food supply. Conversely,
it has been shown that in ewes which are poorly fed the sexual
season is often retarded, and the fertility of the flock reduced. So
also the occurrence of a snowstorm, or other unfavourable climatic
condition, occurring during tupping time will cause a corresponding
scarcity of twin births in the following lambing season. There can
be little doubt, therefore, that the conditions which exist during
tupping time are largely responsible for controlling the fertility of
the flock, and that favourable conditions tend to promote the more
rapid growth and maturation of the follicles in the ovary, and cause
a greater number to discharge their ova during the oestrous periods.

It would appear also that in ordinary agricultural practice the
condition of the ewe is a far more important factor in determining
the number of twin births than that of the ram ; but it is obvious
that the number of ewes which one ram can serve successfully must
depend upon the degree of vigour possessed by him, and that the
keeping of a ram which is partially sterile and yet is turned out
to serve ewes must result in a reduction in the number of lambs (see
below, p. 637).

The effects of nutrition upon the production of ripe follicles in
guinea-pigs have been studied by Leo Loeb l who states that under-
feeding if very pronounced prevents maturation in all cases, and
causes atrophy before the follicles have reached medium size. A
premature solution of the epithelial cells is brought aboiit in this
way, but the connective tissue of the ovary is more resistant to the
effects of underfeeding. The cells which are furthest from the
blood-vessels suffer first. The epithelial cells, however, continue to
multiply as long as they survive, and this is ascribed to a normal
growth stimulus which emanates from the ovum. The result of
poverty of nutrition is more marked in the ovaries of young animals
just as the general effect is greater, but a " hypotypical " condition
can be induced even in old guinea-pigs. In an extreme case of
hypotypical ovaries the connective tissue separating the follicles had
become affected, being undeveloped or lacking, so as to result in a
union of follicles and a consequent polyovular condition.2 Loeb

1 Loeb, "The Experimental Production of Hypotypical Ovaries through
Underfeeding," Biol. Bull., vol. xxxii., 1917.

2 See footnote, p. 121.

636 THE PHYSIOLOGY OF REPRODUCTION

says that the hypotypical ovarian state leads to at least temporary
sterility.

Follicular atrophy is, however, a normal process probably in all
the higher animals (see p. 153), and it is only when it becomes
excessive that it is a cause of sterility, since the number of young
ova and follicles is far larger than that of the young which could
develop. Thus the human ovary is said to contain 20,000 oocytes
at puberty, or sufficient to admit of forty ova being discharged every
month throughout the reproductive period of life. In the rat there
are, according to Arai,1 35,100 ova at birth, but these are reduced
by degeneration to 11,000 after twenty-three days and 6000 by
the sixty-third day. Moreover, according to Robinson,2 in the ferret
the smaller follicles are necessary for providing nourishment for the
larger developing ones.

. Moreover, Hammond 3 has shown that in the domestic animals,
and especially in the pig and tame rabbit, fecundity is apt to be
conditioned rather by the factors controlling development in iitcro
than by the production of ova. The number of eggs matured is
frequently in excess of the nutrition available for them, and this
leads them to atrophy, sometimes while still contained in the ovarian
follicles, but also very frequently as newly fertilised ova or partially
developed embryos.

The effect of external conditions on the rate of follicular ripening
in the rabbit has also been studied by Hammond, who states that in
the wild state the number of eggs discharged increases from January
to April and then decreases. This is similar to what occurs in the
domestic fowl. With tame rabbits the effect is not so marked owing
to the more uniform conditions under which they are kept. The
average number of eggs shed at one period was found to be 5'74 in
wild rabbits and 10*3 in domesticated rabbits, but in the latter
atrophic foetuses are much more common (see below, p. 656).

INFLUENCE OF THE MALE PARENT

It has been suggested that in some males there is a want of
vigour on the part of the spermatozoa which either prevents them
from conjugating with ova or causes abortion of the fertilised ovum
or foetus owing to its being endowed with a reduced vitality.
Stephenson4 refers to cases of bulls which had at one time been

1 Aral, "On the Post-Natal Development of the Ovary, etc.," Amer. Jour,
of Anat., vol. xxvii., 1920.

2 Robinson (A.), "The Formation, etc., of the Graafian Follicle in the Ferret,
etc.," Trans. Roy. Soc. Edin., vol. Hi., 1918.

:t Hammond, " Further Observations on the Factors controlling Fertility
and Foetal Atrophy," Jour. Agric. Science, vol. xi., 1921.

4 Stephenson, " Abortion in Cows," Jour. Roy. Agric. Soc. vol. xxi.
(2nd series), 1885.

FERTILITY 637

"good getters" but were afterwards responsible for cows being
sterile or aborting at different stages of pregnancy, and he explains
them in this way. Hammond l describes what he suggests may have
been another such case of a bull, for he found that the semen of the
animal in question only contained occasional spermatozoa which, in
contrast to those obtained from other bulls, showed no sign of
movement. There can, however, be little doubt that ordinarily
spermatozoa in amply sufficient numbers are ejaculated at one
service to fertilise all the ova discharged by the female. Moreover,
Hammond found that with the male rabbit after repeated coition
(even up to the thirty-seventh time and within eight hours) there
was no reduction in the fertility of the females which were served.
The delay periods, however, between the later copulations were
slightly increased. Contrary to Hammond's results Lloyd-Jones
and Hays 2 had previously found that excessive copulation by the
male rabbit produced a reduction both in the number of pregnancies
and in the size of the litters.

It is said that a good stallion should be able to serve eighty
mares in one season, but Hammond has pointed out that there may
be no reduction in the fertility of the mares even though as many
as 140 are served. At the same time, the records of one province
have shown that the percentage of foals left by different stallions
can vary from twenty-seven to seventy-five.3 The usual proportion
of ewes put to one ram is about fifty, but ram lambs are not
permitted to serve more than about twenty ewes. Similarly with
stallions, when they are two years old they are not allowed to have
intercourse with more than sixty mares as compared with 80 to 120
for adult stallions. It is not suggested, however, that if a larger
number of services were permitted the unions would be sterile, but
that too frequent intercourse has a deteriorating influence on the
vigour of the male. Even yearling stallions are sexually mature
but are never allowed more than fifteen mares, and generally none
at all. •

EFFECT OF PKOLONGED LACTATION

It has been recorded that the continuance of lactation commonly
exerts an inhibitory influence on menstruation in women and on
heat in animals, though this is very far from being invariable (see
p. 69). There can be no doubt that in the case of sows, for
example, early -weaning is conducive to a more frequent recurrence

1 Hammond, loc. cit.

2 Lloyd-Jones and Hays, " Influence of Excessive Sexual Activity in Male
Babbits," Jour. Exp. Zool., vol. xxv., 1918.

3 Marshall and Crosland, " Sterility in Mares, etc.," Jour. Board of Agric.,
vol. xxiv., 1918.

638 THE PHYSIOLOGY OF REPRODUCTION

of oestrus and an increased number of litters (see p. 46). In a
similar way long-continued lactation is believed to reduce the
fecundity of women, who sometimes refrain from weaning their
babies in the belief that by so doing they are less liable to become
pregnant again. Moreover, Haddon's observations l upon the Eastern
Islanders of the Torres Straits show that with these people also
prolonged nursing tends to reduce the size of the families, and that a
single lactation may be continued for three years

EFFECT OF DRUGS

There is little evidence as to the effects of drugs upon egg- or
sperm-production, but innumerable substances have been recom-
mended as cures for impotence.2 Cantharides and various other
drugs are said to produce sexual excitement, but this result is
probably due simply to the increased flow of blood to the generative
organs which these substances induce.3 Wallace says that the
practice adopted by some grooms of giving cantharides to stallions is
strongly to be deprecated. Bloch is disposed to recommend the use
of phosphorus and strychnine in the treatment of impotence in men,
but the most favourable results have been obtained by yohimbine,
an alkaloid prepared from the bark of a West African tree. Bloch
mentions several cases where, in his own experience, treatment by
yohimbine has been entirely successful, and there are numerous
others on record. Many veterinarians also have testified to the
powerful aphrodisiac action of yohimbine, stating further that it is
capable of inducing a condition of heat in domestic animals and
acting as an effective remedy for certain kinds of sterility.

Daels4 found that yohimbine when administered to dogs
produced hypertemia of the generative organs, followed by mucous
and sanguineous discharge, but not true heat. Dr. Cramer and the
present writer5 have made similar observations. We first
administered O'OOS gram of yohimbine twice daily for nearly a
fortnight to each of two anoestrous bitches, the drug been swallowed
in the form of tablets. Marked congestion of the generative
organs followed. On treating rabbits with yohimbine the vulva
and the uterine mucosa became excessively hypersemic, the entire

1 Haddon, Reports of the Cambridge Anthropological Expedition to Torres
Straits, vol. vi., Cambridge, 1908.

2 For the distinction between sterility and impotence see below (p. 644).
For detrimental results of drug action or abnormal treatment on sperm- or
egg-production see also below (p. 647).

3 Bloch, The Sexual Life of our Time, English Translation, London, 1908.

4 Daels, " On the Relation between the Ovaries and the Uterus," Surgery,
Gynaecology and Obstetrics, vol. vi., (February) 1908.

5 Cramer and Marshall, "Preliminary Note on the Action of Yohimbine
on the Generative System," Jour. Econ. Biol., vol. iii., 1908.

FERTILITY 639

generative tract being affected to some extent. The ovaries were
much overgrown by luteal tissue, and degenerate follicles which
are generally so common in rabbits' ovaries were relatively
scarce. Hammond,1 however, failed to get any positive results on
the fertility of rabbits after treatment with yohimbine. We
obtained some evidence that yohimbine may promote mammary
development and the secretion of milk.

EFFECTS OF IN-BREEDING AND CROSS-BREEDING

The fact that in-breeding may result in a reduced fertility has
been already discussed in dealing with the significance of the
fertilisation process (pp. 215-220).2 It was then pointed out that
a tendency towards sterility may be associated with a constitutional
loss of vigour. In the same place it was mentioned further that
cross fertilisation between organisms which are allied but belong
to different strains often results in an increased fertility, but that
cross fertilisation between different species is frequently difficult
to accomplish while there is every gradation between a mere
disinclination towards gametic union and complete cross sterility.

The differences in fertility between varieties and species when
crossed are discussed at some length by Darwin,3 who summarises
his general conclusions under seven heads. First, the laws
governing hybridisation in plants and animals are practically
identical. Secondly, there are all degrees of cross infertility.
" Thirdly, the degree of sterility of a first cross between two species
does not always run strictly parallel with that of their hybrid
offspring. Many cases are known of species which can be crossed
with ease, but yield hybrids excessively sterile ; and conversely
some which can be crossed with great difficulty, but produce fairly
fertile hybrids. This is an inexplicable fact on the view that
species have been specially endowed with mutual sterility in order
to keep them distinct." Fourthly, the degree of sterility is often
different in the two sorts of reciprocal crosses between the same
species, and hybrids produced from reciprocal crosses sometimes
differ in their degree of sterility. " Fifthly, the degree of sterility
of first crosses and of hybrids runs, to a certain extent, parallel with
the general or systematic affinity of the forms which are united.

1 Hammond, loc. cit., 1921.

2 A method of measuring the degree of in-breeding practised in any
particular case has been devised by Pearl. It is based on the simple and
definite conception that an in-bred animal has fewer different ancestors than
one which is not in-bred, and coefficients of 'in-breeding have been constructed.
For details of the method see Maine Agric. Exp. Station Bulletins, 215 and 243,
Orono, 1913 and 1915.

3 Darwin, loc. cit. See also Origin of Species, Gth Edition, London, 1872.

640 THE PHYSIOLOGY OF REPRODUCTION

For species belonging to distinct genera can rarely, and those
belonging to distinct families can never, be crossed. The parallelism
is, however, far from complete ; for a multitude of closely allied
species will not unite, or unite with extreme difficulty, whilst other
species, widely different from one another, can be crossed with
perfect facility. Nor does the difficulty depend on ordinary
constitutional differences, for annual and perennial plants, deciduous
and evergreen trees, plants flowering at different seasons, inhabiting
different stations, and naturally living under the most opposite climates,
can often be crossed with ease. The difficulty or facility depends
exclusively on the sexual constitution of the species which are
crossed; or on their elective affinity." Sixthly, cross sterility
between species may depend possibly in certain cases upon distinct
causes, such as deterioration due to unnatural conditions to which
the hybrid embryo may be exposed in the uterus, egg, or seed of the
mother. " Seventhly, hybrids and mongrels present, with the one
great exception of fertility, the most striking accordance in all other
respects; namely, in the laws of their resemblance to their two
parents, in their tendency to reversion, in their variability, and in
being absorbed through repeated crosses by either parent form."
It is obvious, however, that this last conclusion requires some
modification in the light of recent Mendelian research.

Darwin maintains further that the cross fertility which exists
between the different varieties of various species of domesticated
animals, in spite of their great divergence in external appearance,
is the direct effect of domestication which eliminates the tendency
towards mutual sterility. In this way " the domesticated descendants
of species, which in their natural state would have been in some
degree sterile when crossed, become perfectly fertile together." Both
Darwin and Wallace lay stress upon the apparent existence of a
parallelism between crossing and change of conditions in so far as
these affect the power to reproduce. •' Slight changes of conditions
and a slight amount of crossing are beneficial ; while extreme changes,
and crosses between individuals too far removed in structure or
constitution, are injurious." l Furthermore, domestic animals are
less susceptible to the influences of changed conditions of existence
than wild animals, a fact which finds a parallel in the absence of
sterility between domesticated varieties of the same species.

It is now clear that Darwin's views on in-breeding and on the results
of that process must be modified in the light of recent Mendelian
investigation, for, as already shown in an earlier chapter of this book,
there is a growing body of evidence to show that different degrees of
productivity down to complete sterility can be inherited as though

1 Wallace (A. R), Darwinism, London, 1897.

FERTILITY 641

they were Mendelian units. In the light of this conception the
effects both of in-breeding and of cross-breeding would seem to
acquire a new signification. It has been established that in some
insects (Drosophila) complete sterility may be a sex-linked character,
and the same is apparently true of the male tortoiseshell cat. It is
suggested that in the famous Duchess family of Shorthorn cattle
bred by Bates and which eventually became extinct, there was a
factor for sterility present, and this as a result of close in-breeding
kept on reappearing with increased frequency until no more fertile
individuals were produced. It has been shown that with Drosopkila,
and also with the guinea-pig, a high degree of fertility can be
maintained in successive generations of in-breeding by selecting from
the more fertile individuals. Further, there is direct cytological
evidence that in Drosophila sterility is correlated with the absence of
a particular chromosome.1

And conversely the increased vigour and fertility apparently
brought about by cross-breeding and heterozygosis may be "due to
the establishment of a more excellent factor-complex rather than
to any mysterious stimulation effect of the heterozygous condition." 2
At the same time it is possible that the reproductive cells even in
their hereditary composition are capable of being affected by their
environment, and it is reasonable to suppose that in the unicellular
organisms at any rate new and more favourable surroundings, acting
in conjunction with an appropriate factor-complex, may have a stimu-
lating and favourable influence on fertility.

The sterility of hybrids is a very common phenomenon and has
received a cytological interpretation. Such infertility is, however,
by no means invariable.

Wallace has cited several cases in which it has been shown that
hybrids between distinct species are fertile inter se. Such cases are
the hybrids between the domestic and Chinese geese, and the various
hybrids between the different species of the genus Canis. A ease of
a fertile hybrid between a lion and a jaguar has been recorded also.
The various members of the family Bovidse are known to hybridise
and to produce fertile offspring even though the parents belong to
what are ordinarily regarded as different genera. The cow (Bos taurus)
gives fertile male and female hybrids when crossed with the zebu
(Bos indicus). With the yak (Bibos yrunnicus), the gaur (Bibos gaurus),
the gayal (Bibos frontalis) and the bison (Bison americanns) the cow
has fertile female hybrids but sterile males.3 The hybrids between

1 For an admirable discussion of the subject see Babcock and Clausen,
Genetics in Relation to Agriculture, New York, 1918. This work contains many
references. See also Morgan, Heredity and Sex, New York, 1913.

* Babcock and Clausen, loc. cit.

3 Babcock and Clausen, loc. cit.

642 THE PHYSIOLOGY OF REPRODUCTION

the cow and Bison bouasus are similar.1 These and other observations
show that sterility among hybrids between closely allied species,
although usual, is very far from being universal.2 Similar cases have
been recorded from among plants.

The cause of sterility in hybrid organisms is still to a large
extent an open question. In some cases the generative organs are
atrophied or imperfectly developed, while in most, if not all sterile
hybrids, the gametes are not developed. For example, Iwanoff3
states that hybrids between the horse and the zebra do not possess
spermatozoa, though able to perform the sexual act.

It has been suggested that the sterility is due to irregularities in
the mechanics of division in the germ-cells. " When we recall that
at one stage in the development of the germ-cells there may be a
pairing and subsequent fusion of the maternal and paternal chromo-
somes, we can readily imagine that any differences in their behaviour
at this time might lead to disastrous results." 4

It has been shown that irregular reduction divisions occur in the
male, and that in hybrid pheasants a degeneration of germ-cells
begins in synapsis. In some hybrids the number of chromosomes
derived from each parent is different, but as Babcock and Clausen
point out, the difficulty must be fundamentally physiological, since it
is just as pronounced in hybrids between species having the same
number of chromosomes.

INHERITANCE OF FERTILITY

That fertility is a racial characteristic, and'consequently is capable
of hereditary transmission, is a fact that is generally accepted.
Among sheep, for example, some breeds, like the Dorset Horns, the
Hampshire Downs, and the Limestones, are notoriously prolific, while
other varieties, like the Scotch Blackfaced, are relatively infertile.5
Furthermore, there is a considerable amount of evidence that in each
breed there are particular strains of related individuals which have
a higher degree of fertility than the average, and that flockmasters,

1 Iwanoff, " Sur la Feconditu de Bison bonasus x Bos taunts" C. R. de In Soc.
de Biol., vol. Ixxv., 1913. See also other papers by Iwanoff (C. R. de la So<\ de
fiiol., vol. Ixx., 1911 ; Biol. Cent., vol. xxxi., 1911 ; and Zeitsch. f. ind. Abst. u.

Vererbungslehre, vol. xvi., 1916).

2 See Suchetet, "Problemes Hybridologiques," Jour, dc I'Anat. et la 1'lii/s.,
vol. xxxiii., 1897. Dewar and Finn, The Making of Species, London, 1909.

3 Iwanoff, " Untersuchungen iiber die Unfruchtbarkeit von Zebroiden,"
Biol. Cent., vol. xxv., 1905. "De la Fecondation Artificielle chez les
Mammiferes," Arch, des Sciences Biologiques, vol. xii., 1907.

4 Morgan, Experimental Zoology, New York, 1907. See also Heredity and
Sex, New York, 1913.

5 The Leicester breed of sheep is characterised by a relatively low fertility,
and this is said to be due to the preference that was shown to large single
lambs at the time when high prices ruled, and the consequent discarding of
ewes which bore twins. See Wallace (R.), loc. cit.

FERTILITY 643

by breeding from twin ewes and employing the services of twin rams,
have been able permanently to increase the fertility of their stock.1

The inheritance of fertility in man and also in thoroughbred
horses has been investigated statistically by Karl Pearson and his
biometrical collaborators,2 to whose memoir the reader is referred for
a full discussion of the mathematical details and the conclusions
which are arrived at. It is there shown, among other facts, that the
woman inherits fertility equally through the male and female lines.
Among thoroughbred race-horses the fecundity was first ascertained
(i.e. the ratio of foals surviving to be yearlings to the total number of
foals possible under the given conditions), and the following general
conclusions were afterwards reached: (1) Fecundity is inherited
between dam and daughter, and (2) Fecundity is also inherited
through the male line, i.e. the sire hands down to his daughter a
portion of the fertility of his dam. Thus fecundity, which is, of
course, a latent character in the male, was measured for a horse and
for his sire, and was found to be strongly inherited.

"More recently Kommel and Phillips 3 have shown mathematically
that there is an actual correlation between the size of the litter in
two successive generations of Poland China sows, the productiveness
being a character which is transmitted from mother and daughter.

On the other hand, Pearson,4 from studying Weldon's records of
mice-breeding experiments, failed to find a sensible parental correlation
in regard to the size of the litters. Pearl and Surface,5 as a result of
a statistical investigation on egg-production in Barred Plymouth
Kock fowls, found no evidence of the inheritance of fecundity so long
as simple mass selection was practised. For this breed the capacity
for egg-producing was not increased by this method, but tended
rather to be diminished.

Pearl next started to analyse his results on the assumption that
Mendelian factors might exist which were themselves concerned
with different degrees of fertility. He found that the winter egg-
production bore a direct relation to the total egg - production

1 Marshall, " Fertility in Scottish Sheep," Trans. Highland and Agric. Soc.,
vol. xx., 1908.

2 Pearson, Lee, and Bramley -Moore, "Mathematical Contributions to the
Theory of Evolution : VI , Genetic (Reproductive) Selection, Inheritance of
Fertility, etc.," Phil. Trans., A., vol. cxcii., 1899.

3 Rommel and Phillips, " Inheritance in the Female Line of Size of Litter
in Poland China Sows," Proc. Ainer. Phil. <S'oc., vol. xlv., 1907.

4 Pearson, "On Heredity in Mice, from the Records of the late W. F. R.
Weldon," Biometrika, vol. v., 1907.

5 Pearl and Surface, " Data on the Inheritance of Fecundity obtained from
the Records of Egg Production, etc.," Maine Agric. Exp. Station Bulletin
No. 166, Maine, 1909. Pearl, " A Biometrical Study of Egg Production in
the Domestic Fowl," U.S. Dcpt. of Agric., Bureau of Animal Industry, Bulletin
No. 110, Washington, 1909.

644 THE PHYSIOLOGY OF REPRODUCTION

throughout the year. An average winter output of less than
thirty eggs he found it useful to denote by one factor (L). This was
ascertained to be dominant over the allelomorph (/) which is
present in fowls laying no winter eggs. It is not sex-linked. A
second fecundity factor (M) denotes a winter egg-production of more
than thirty (even up to ninety) provided that it is present along with
the first factor (L). Without it the egg-production is still less than
thirty. This second factor (M) is sex-linked since it is carried only
by ova which give rise to males. The high egg-production, therefore,
is transmitted by the cock whose female offspring manifest it in the
next generation.1 By acting on this hypothesis Pearl was able
substantially to increase the productivity of the Barred Plymouth
Kock fowls, and although the theory has been criticised it must be
admitted that it is extremely difficult to explain the results in any
other way. As to what precise physiological signification is to be
attached to a factor for fecundity is a point which' we are not yet
in a position to discuss, but the conception is not necessarily more
difficult than that of any other kind of Mendelian factor.

CERTAIN CAUSES OF STERILITY

A detailed account of the various pathological conditions which
are capable of inducing sterility is outside the scope of this work.
The medical publications dealing with the subject form a very
considerable literature,2 while the causes of sterility in animals are
discussed, though somewhat unsatisfactorily, in many of the veterinary
text-books. It may not be out of place, however, to refer briefly to
certain of the conditions which are known to induce sterility in man
and also in animals.

In the case of the male an incapacity to procreate is due either
to impotence (i.e. inability to perform the sexual act), or to sterility
(using the term in the more restricted sense, implying an absence of
spermatozoa). Impotence rnay result from (1) absence of sexual
desire, (2) absence of the power of erection and consequent intro-
mission, (3) absence of the power of ejaculating the seminal fluid

1 Pearl, "The Mode of Inheritance of Fecundity in the Domestic Fowl,"
Jour, of Exp. ZooL, vol. xiii., 1912. See also papers in Atner. Nat., vols. xlv.,
xlvi., xlix., and 1., 1911-16. For Castle's criticism see Amer. Nat., vol. xlix.,
1915. For work on seasonal distribution in egg-production, see Pearl and
Surface, U.ti. Dept. of Agric., Bureau of Animal Industry, Bulletin 110, Part 2, 191 1.
For further experiments, etc., on fecundity in fowls see recent papers by Pearl,
Curtis, etc., in Biol. Bull., Jour, of Agric. Research, Arch. f. Entwick.-Mech., and
various American journals. See also Goodale and M'Mullen, "The Bearing of
Ratios on Theories of the Inheritance of Winter Egg Production," Jour. <>/'
Exp. Zool., vol. xxviii., 1919.

2 Muller (P.), Die Unfruchtlarkeit der Elte, Stuttgart, 1885. This work
contains a bibliography.

FERTILITY 645

into the vagina, and (4) absence of the ability to experience pleasure
during the act of coition, and at the time of the emission of the
semen. Or, according to another classification, the causation of
impotence may be either anatomical, physiological, pathological, or
psychological. Among the anatomical causes may be mentioned
defects and deformities in the penis. The physiological and
pathological causes include incomplete erections, premature ejacula-
tions, diseases of the brain and spinal cord (and more particularly of
the centres for the performance of the sexual act), besides such
diseases as albuminuria, or prolonged diabetes. The psychological
causes include fear, repugnance, want of confidence, etc.1

Complete sterility, i.e. inability to procreate owing to the absence
of fertile semen, is due to various causes, and may be either
congenital or acquired. Congenital sterility occurs when the
testicles are never developed, or are so imperfectly developed that
they fail to produce ripe spermatozoa. In cases of incomplete
descent of the testicles fertility is rare, but it may exist for a short
time as in young men from twenty to twenty-three years of age.
Acquired sterility results from the various diseases to which the
generative organs are subject, such as tubercle, syphilis, attacks of
inflammation, urethral stricture, epididymitis, prostatic enlargement
or diminution, etc.2

A more special cause of sterility in men is one which operates in
the case of workers with radium or the Kontgen rays. Several years
ago Albers-Schonberg :{ noticed that the X-rays induced sterility in
guinea-pigs and rabbits, but without interfering with the sexual
potency. These observations have been confirmed by other
investigators,4 who have shown, further, that the azoospermia is due
to the degeneration of the cells lining the seminal canals. In men it
has been proved that mere presence in an X-ray atmosphere
incidental to radiography sooner or later causes a condition of
complete sterility, but without any apparent diminution of sexual
potency.5 As Gordon observes, for those working in an X-ray
atmosphere adequate protection for all parts of the body not directly
exposed for examination or treatment is indispensable, but, on the
other hand, the X-rays afford a convenient, painless, and harmless

1 Corner, Diseases of the Male Generative Organs, London, 1907.

- Corner, Joe. cit.

:i Albers-Schonberg, " Ueber eine bisher unbekannte Wirkung der Rontgen-
strahlen auf den Organismus der Tiere," Miinchener med. Wwhensc.hr,, No. 43,
1903.

1 4 See Gordon, " Diseases caused by Physical Agents," Osier's System of
Medicine, vol. i., London, 1907. See also Regaud and Dubreuil, " Action des
Rayons de Rb'ntgen sur la Testicule de la Lapin," C. R. de la Soc. de Biol.,
vol. Ixiii., 1907.

5 Brown and Osgood, " X-Rays and Sterility," A mer. Jour, of Surgery,
vol. xviii., (April) 1905.

646 THE PHYSIOLOGY OF REPRODUCTION

method of inducing sterility, in cases in which it is desirable to effect
this result.1

The various causes of sterility in women are discussed at consider-
able length by Kelly,2 as well as by other writers 3 on gynaecology.
Kelly mentions the following conditions as likely to be found
associated with sterility: Gonorrhoeal infection of Skene's or
Bartholin's gland, stricture of the vagina or cervix, the presence of
a uterine polyp, a uterine fibroid tumour, a parovarian cyst, or a
nodular salpingitis (from gonorrhoea or tuberculosis), atresia of the
uterine tube (from inflammation), and the existence of ovarian
adhesions. These, and other causes of sterility, and the methods of
treatment to be adopted, are fully dealt with by Kelly.

Sterility in animals, as in man, is brought about by a variety of
causes,4 some of which are incurable, but others, such as constriction
of the os uteri, are capable of treatment. In the case of cattle great
difficulty is often experienced in getting the cows to breed after
attacks of contagious abortion, and this is said to be due to an acid
condition of the vaginal mucous membrane. In order to remedy
this, injections of dilute solutions of bicarbonate of soda are employed
and are found to be effective. Others recommend that the uterus
should be injected with solutions of perchloride of mercury.5

Sterility in mares and cows and other animals is often due to
structural or functional defects in the vagina, os uteri, or cervix.
These may sometimes be overcome by resorting to artificial insemina-
tion, the methods of which are described below.6

Furthermore, sterility among cows may be contagious owing to
the disease known as infectious granular vaginitis, which is primarily
an acute inflammation of the vulva and vagina. It is commonly
communicated by a contaminated bull in which the penis and sheath
are affected. Similarly a bull may become diseased by serving an
infected cow, and in this way vaginitis may spread through an entire

1 Gordon, Joe. cit. It has been shown also that the Rontgen rays may
induce degeneration of the follicles, corpora lutea, and interstitial cells in the
ovaries and cause sterility in the female. See Bouin, Ancel, and Villemin
(C. R. de la Soc. de Biol., vol. Ixi., 1906), Bergomie and Trabondeau (C. It. de la
Soc. de Biol., vol. Ixii., 1907), and Specht (Arch. f. G'ynak., vol. Ixxviii., 1907).

- Kelly, Medical Gynecology, London, 1908.

3 See especially Duncan, Sterility in Women, London, 1884, and Miiller,
loc. cit. Duncan states his opinion that probably ten per cent, of the marriages
in Great Britain are sterile.

4 Fleming, Text-book of Veterinary Obstetrics, London, 1878.

5 Wallace (R.), loc. cit. According to Knowles (" Sterility of Mares and
Cows," Amer. Veterinary Review}, "sub-acute and chronic cervical hypertemia
are probably the most frequent and fruitful causes of temporary sterility, due
in an astonishingly large number of instances to continually recurring
abortions."

6 Constriction of the os uteri in cows may often be remedied by the employ-
ment of a large probe followed by the finger, or better still by a specially
devised instrument known as a dilator. See Wallace (R.), loc. cit.

FERTILITY 647

herd. During recent years contagious sterility has been very
common in Switzerland and Germany, and there is evidence of its
existence in England. Antiseptic disinfection is useful, but
experience has shown that even when treated infectious vaginitis
often runs a prolonged course. Nevertheless, a complete cure
usually takes place after some months, this recovery being indicated
by the cessation of the muco-purulent discharge and the recurrence
at normal intervals of the oestrons periods.1

Deficient, excessive, or unfavourable nutrition, change of
environment, in-breeding, etc., as sources of infertility, have been
already discussed. (For persistence of corpus luteum as a cause see
p. 373.)

Sterility may also be induced experimentally in animals by
drugs or toxic substances. Rats treated with alcohol show abnormal
sperm formation or atrophy of the seminiferous tubules. Guinea-
pigs similarly treated have smaller litters and degenerate young.
After administering thorium to newts the fertilised ova only
partially develop.2 Quinine sulphate when fed to laying ring-doves
reduces the amount of yolk in the egg besides decreasing the
deposition of albumen,3 and other instances of a similar kind might
be quoted, illustrating the susceptibility of the reproductive organs
to the action of abnormal substances.

ARTIFICIAL INSEMINATION AS A MEANS OF OVERCOMING STERILITY

Artificial insemination as a means of overcoming certain forms
of sterility has been employed by various medical men from Hunter's
time downwards. In the case treated by Hunter himself,4 the
husband of the woman experimented upon was affected with
hypospadias. The semen was injected into the vagina, conception
followed, and a child was afterwards born. Sims 5 recorded a case of
a woman who suffered from dysmenorrhoea and a deformed uterus,
and who had been married for nine years without having children.
Artificial insemination was resorted to, pregnancy ensued, and a child
was born in due time. Numerous other cases are cited by Heape 6
and Iwanoff,7 to whose papers the reader is referred for bibliographies
of the subject.

1 McFadyean, "Sterility in Cows," Jour. Royal Agric. ,SVw., vol. Ixx., 1909.

2 See Hammond, he. cit., 1921.

3 Eiddle and Anderson, "Studies on the Physiology of Reproduction in
Birds," VIII., A met: Jour, of P/tysiol., vol. xlvii., 1918.

4 This case is described by Home, Phil. Tra-)>*., 1799. (See p. 176,
Chapter V.)

5 Sims, Notes Clwiques sur la Chirurgie Uterine, Paris, 1866.

G Heape, "The Artificial Insemination of Mammals, etc.," Proc. Roy. Soe.,
vol. Ixi., 1897.

7 Iwauoff, "De la Fecondation artificielle chez les Mammiferes," Arch, des
Sciences Bioloyiqucs, vol. xii., 1907.

648 THE PHYSIOLOGY OF REPRODUCTION

The method adopted by gynaecologists who have practised
artificial insemination is to inject seminal fluid into the uterus by
means of a syringe, the fluid in most cases being obtained from
the vagina of the same individual shortly after coitus. In this
way it has been found possible to overcome such structural defects
as constriction or undue rigidity of the cervix or hypertrophy of
the lips of the external os uteri. By modifying the method by
which the semen is obtained, it has proved possible to induce
pregnancy in cases of abnormal vaginal secretion where the
spermatozoa are ordinarily killed before they can effect an entrance
into the uterus, and in other cases where there is an inability on
the part of the vagina to retain the semen after coitus.

Artificial insemination has frequently been practised on mares
with a view to overcoming certain forms of sterility, and considerable
success has been attained. " Such defects as flexion or constriction
of the canal of the cervix ; rigidity of the cervix ; hypertrophy of
the lips of the external os, and the formation of false membranes
which may effectually close the orifice; inability to retain sper-
matozoa in the vagina, owing to abnormal shortness of the organ
or to violent muscular contraction, after coitus ; a want of sufficient
muscular power; abnormal structure or size of the cervix or os
uteri, which prevent the free action of the functions of the cervix ;
occlusion of the os owing to spasmodic contraction of the muscles
of the cervix during coitus ; abnormal or excessive vaginal secretions,
which may kill or deleteriously affect the spermatozoa, etc., may be
overcome by artificial insemination."1 Heape, and more recently
Iwanoff,2 have cited numerous cases in which mares have been got
in foal successfully by artificial insemination.

The actual methods employed are described by these writers.3
The most usual plan is to allow the stallion to serve the mare in
the ordinary way, and then, immediately afterwards, to insert a
syringe into the vagina, and draw up into it some of the seminal
fluid which is caused to collect in a depression or pocket made in
the vaginal floor by the pressure of the finger tips. The same mare
can then be inseminated by injecting the fluid so obtained into the
uterine cavity, or the semen can be utilised for impregnating other

1 Heape, "The Artificial Insemination of Mares," Veterinarian, 1898. In
the writer's experience incapacity to retain the semen after service is a
common cause of sterility. It is sometimes possible to catch the fluid as it
is evacuated from the vagina with a beaker, and then to inject it through
the os uteri.

2 Iwanoff, for. cit. This important memoir, besides containing descriptions
of the author's own experiments, gives a very full account of the literature of
artificial insemination. See also Iwanoff, Jour, of Agric. 8ci., vol. xii., 1922.

3 See also a booklet edited and published by Huish The Cause and Remedy
for Sterility in Mares, Cows, and Bitches, London.

FERTILITY 649

mares. Another method is to collect the semen in gelatine capsules
which are placed in the vagina before coitus, and then, when they
have been filled, to close their lids and insert them in the interior
of the uterus, where the heat of the body gradually melts the
gelatine and sets free the spermatozoa. By such means as this
several mares may be impregnated as a result of one service by a
stallion. In some cases pieces of sponge have been employed instead
of gelatine capsules.1

Artificial insemination has been of considerable use also in
remedying sterility in cows as well as in dogs.2

Several investigators by employing artificial insemination have
been successful in getting crosses between animals belonging to
varieties in which the disparity in size is so great that coitus
between them is difficult or impossible. Thus, Plonnis3 in 1876
successfully inseminated a lap-dog with the semen of a setter, and
obtained a pup which in most of its points resembled its father.
Allbrecht4 performed a similar experiment and obtained a similar
result. More recently Heape5 has described some experiments
carried out by Millais, in which bloodhounds were inseminated with
spermatozoa obtained from Basset hounds (a much smaller breed),
litters of cross-bred pups being produced.

Iwanoff0 has recorded an experiment in which he successfully
inseminated a white mouse with the spermatozoa of a white rat.
Two hybrid young ones were produced after a pregnancy lasting
twenty-seven days. They were intermediate in size between rats
and mice. This is the first record of a cross being obtained between
two species so different in size as the rat and the mouse, coitus
between them being practically impossible. Furthermore, Iwanoff
has successfully employed artificial insemination to obtain hybrids
between horses and zebras (a cross which is often difficult to get
by the normal method owing to the liability of the animals to
refuse service).

The problem of preserving spermatozoa alive in artificial media
is one which has only recently been investigated systematically. It
is evident that were one in a position to send semen to a distance

1 For further information and practical details see Iwanoff, Die Kiinstliche
Befruchtung der Haustiere, Hannover, 1912. For experiments with fowls see
Iwanoff, " Experiences sur la Fe"condation Artificielles des Oiseaux," C. R. de la
Soc. de Biol., vol. Ixxv., 1913.

2 See Huish, loc. cit.

3 Plonnis, "Kiinstliche Befruchtung einer Hiinden, etc.," Inaug.- Dissert.,
Eostock, 1876.

4 Allbrecht, "Kiinstliche Befruchtung," Wochenschr. f. Tkierheilkunde und
\Tiehzuc/it, Jahrg. xxxix.

5 Heape, " The Artificial Insemination of Mammals," Proc. Roy. Soc., vol. Ixi.,
1897.

6 Iwanoff, lor. cit.

21 A

650 THE PHYSIOLOGY OF REPRODUCTION

and then successfully inseminate, it would be a very great economic
advantage to the breeding industry.

That the spermatozoa of the bull may survive for as long as
twelve days within the removed testicle if the latter be kept at a
temperature a little above freezing point, has been shown by Iwanoff.
Outside the tissues of the animal Iwanoff found that spermatozoa
may preserve their motility for some hours in solutions of sodium
chloride, barium chloride, and potassium nitrate, but the exact lengths
of time do not appear to be stated, neither is the temperature
recorded. Ochi l and Sato 2 confirmed these results and found further
that the artificial medium was improved if an isotonic solution of
glucose was added. They state also that oxygen in moderate amounts
is helpful in preserving the life of the spermatozoa. Yamane 3 gives
an account of successful experiments with injecting horse's semen
diluted with physiological salt solution and glucose, but the semen
was used immediately after dilution and not kept in the artificial
medium. Wolf,4 working with rabbits' semen, found that for main-
taining the vitality of the spermatozoa two conditions were necessary ;
first, the reaction of the fluid should be as near that of normal blood
as possible ; and secondly, a sufficiency of " buffer salts " should be
present in order to prevent any great change in reaction due to
metabolism of the spermatozoa themselves. Wolf's general con-
clusion is that with " the combination of a properly balanced physio-
logical saline solution with an isotonic glucose solution, a sufficiency
of oxygen and a careful regulation of the hydrogen-ion concentration,
it is quite possible to keep these cells in a condition in which
motility can be restored on raising to body temperature, provided
that in the interval they are kept at a temperature near 0° C." In
such an environment the spermatozoa could retain their potential
motility for nine days.

ABORTION

Abortion is often an important factor in determining a low
fertility, but its frequency of occurrence shows a considerable range
of variation.

With women the frequency of abortion to birth at full term is

1 Ochi, "Physiological Studies on Spermatozoa, especially its Life Duration,"
Act(e Scholce Med., Univ. Imp. in Kioto, vol. i., 1916.

2 Sato, "On the Life Duration of the Horse Spermatozoa outside of the
Body," Actce Scholce Med., Univ. Imp. in Kioto, vol. i., 1916. -

3 Yamane, "Studien iiber die Physikalische und Chemische Beschaffenheit
des Pferdesperuias, etc.," Jour, of Coll. Aqric., Hokkaido Imp. Univ., vol. ix.,
1921.

4 Wolf, "The Survival of Motility in Mammalian Spermatozoa," Jour, of
Agric. Science, vol. xi., 1921.

FERTILITY 651

said to be from one in five to one in ten.1 According to the records
of Franz2 for the maternity hospital at Halle, the percentage of
cases in which abortion occurred was 15 '4. Williams3 expresses
the opinion that in ordinary private practice every fifth or sixth
pregnancy usually ends in abortion, and that the percentage would
be considerably increased if one reckoned the early cases in which
there is a profuse loss of blood following a retardation of the
menstrual period, the actual fact of abortion being often obscured.

Excepting in the case of sheep, there are no satisfactory data on
which to estimate the frequency of abortion among the different
kinds of domestic animals, but there can be no doubt that it is of
common occurrence, and that it occasions much loss to breeders.
For various varieties of English sheep Heape4 found that the
percentage of abortion experienced by 300 flockmasters varied
from nothing to 23'75, while the percentage for 85,878 ewes was
2'39. The statistics showed that Dorset Horn and Lincoln breeds
suffered most from abortion, the losses from this cause being

O

respectively 4'11 per cent, and four per cent. The Southdown
breed were found to occupy an intermediate position (the percentage
of abortion being 2'86 per cent.), while the other breeds investi-
gated showed a smaller percentage of abortion. Among Scottish
breeds the percentage of aborting ewes does not generally exceed
two per cent., as far as could be ascertained ; but with Blackfaced
ewes it may be as much as five, or even a considerably higher
number, as a consequence of any special adverse circumstance.5
It is possible, however, that the percentages of abortion are actually
somewhat higher than they appear, since its occurrence during the
early stages of pregnancy is not readily detected, and consequently
some of the ewes which were entered in the statistical returns as
barren may in reality have aborted.

Among cattle in Great Britain the frequency of abortion,
according to Heape,6 is not less than ten per cent, of the total
number of animals selected for breeding, and there can be no doubt
that in certain districts it is often very much higher, especially
where contagious or epidemic abortion occurs. Heape states further
that from ten to twelve per cent, of abortion is not unusual in herds
in which no contagious abortion is proved to exist.

There are no data available on which to compute the frequency

1 Kelly, loc. cit.

2 Franz, "Zur Lehre des Aborts," Hegar's Beitrage, vol. L, 1898.

3 Williams, Obstetrics, London, 1904.

4 Heape, " Abortion, Barrenness, and Fertility in Sheep," Jour. Royal Agric.
Soc., vol. x., 1899.

5 Marshall, " Fertility in Scottish Sheep," Trans. Highland and Agric. Soc.,
vol. xx., 1908.

6 Heape, The Breeding Industry, Cambridge, 1906.

652 THE PHYSIOLOGY OF REPRODUCTION

of occurrence of abortion among horses, but the experience of
breeders shows that the losses arising from this cause are very
considerable, and that they are greatest amongst the better-bred
animals. One of the earlier reports of the Eoyal Commission on
Horse-Breeding stated that in this country in any given year no less
than forty per cent, of the mares chosen for breeding fail to produce
foals, but to what extent this result is due to sterility or how far it
may be ascribed to abortion does not appear to have been ascertained.

The causes of abortion are diverse, and may be mechanical,
psychological, physiological, or pathological. Deliberate abortion
among civilised European nations is a criminal offence punishable
by law, but nevertheless is not infrequently carried out. In
Oriental countries and among savages abortion is practised more
openly. The more usual means are drugs (ergot, ethereal oil of
juniper, yew, turpentine, camphor, cantharides, aloes, etc.),1 but none
of these is infallible, and owing to their toxic properties their use
is often accompanied by danger. Haddon2 says that among the
Eastern Islanders of the Torres Straits abortion is procured by
the leaves of the shore convolvulus and certain other plants. Also
the old women give the younger women young leaves of the
argerarger (Callicarpa sp.}, a large tree with inedible fruit, and bok,
a large shrub. When a woman's body is saturated with the juice
from the leaves, she is believed to be proof against fecundity, and
can indulge in sexual intercourse without fear of becoming pregnant.
Probably the toxic substances introduced cause abortion at very
early stages of pregnancy, or even inhibit pregnancy at the very
outset. Abortion is sometimes procured by purely mechanical
means — e.g. blows, massage, hot injections,3 carrying heavy loads,4
etc. But although mechanical and psychological influences, both
voluntary and involuntary, play a part in bringing about abortion,
they are probably less frequently concerned in the process than
pathological conditions existing either in the embryo or in the
maternal organism.

Among the causes of abortion in women Kelly5 mentions
haemorrhage of the chorion, imperfect vascularisation of the amnion,
hydatiform degeneration of the chorion, circulatory disturbances
caused by heart lesions in the mother, various infections of the
mother (notably syphilis), psychic disturbances, and excessive
cohabitation, acute poisoning (by alcohol, phosphorus, lead, etc.),

1 Bloch, loc. cit.
- Haddon, loc. cit.

3 Bloch, loc. cit.

4 Haddon, loc. cit.

6 Kelly, lod. cit. See also Oliver, "The Determinants of Abortion," Brit.
Ned. Jour., 30th November 1907.

FERTILITY 653

and various diseases of the generative organs, such as endometritis,
decidual inflammation, polypoid thickening, etc. It is stated that
the excitability of the nerve centres which control the movements
of the uterus and the tendency to uterine congestion are greatest
at the epochs which would have been menstrual periods if pregnancy
had not occurred, and consequently that abortion is especially
common at these dates.1 The membra'nes are usually cast off with
the foetus, but the decidua is said in some cases to remain, and to
regenerate a normal uterine mucosa. The expulsion of the foetus
and membranes is accompanied by "pains" comparable to those
occurring in normal parturition, the two processes having a general
similarity, which is closer if abortion takes place in the later part
of pregnancy. There is generally also a considerable loss of blood.
After the expulsion the haemorrhage and pains cease, and a process
of puerperal involution sets in.

In horses abortion is probably most frequent during the period
from the sixth to the ninth week of pregnancy. This is explained
by Ewart 2 as being due to the fact that about this time the embryo
loses its primitive attachment to the uterus before acquiring its more
permanent connection by means of the allantoic villi, which are only
beginning to be numerous. The yolk-sac, which in the marsupial is
the organ of foetal nourishment throughout the whole of pregnancy,
in the case of the horse ceases to provide a sufficient supply at about
the end of the seventh week ; but the horse embryo, instead of being
born at this period, like the marsupial, acquires new and more
efficient structures in the allantoic villi. " At the end of the third
week of gestation, when the reproductive system passes through
one of its periods of general excitement, about one-fourth of the
embryonic sac probably adheres to the uterus; but at the end of
the sixth week, when another wave of disturbance arrives, all the
grappling structures are at one pole. Hence there is probably more
chance of the embryo ' slipping ' at the end of the sixth than at the
end of the third week. About the end of the seventh week the
supply of nourishment by means of the yolk-sac is coming to an end,
and there is perhaps still about this time an hereditary tendency for
the embryo to escape. Unless the new and more permanent nutritive
apparatus is provided, unless a countless number of villi rapidly
sprout out from the allantois, the embryo will die from starvation
during the eighth week, and in a few days be discharged. It may
therefore be taken for granted that there is a certain amount of
danger at the end of the third and sixth weeks, but that the most
critical period is about the end of the seventh or beginning of the

1 Galabin, Manual of Midwifery, 6th Edition, London, 1904.

2 Ewart, A Critical Period in the Development of the Horse, London, 1897.

654 THE PHYSIOLOGY OF REPRODUCTION

eighth week ; for unless the villi appear in time, and succeed in
coming into sufficiently intimate relation with the uterine vessels,
the developmental process is of necessity for ever arrested."

Ewart discusses briefly the external conditions and circumstances
which are likely to lead to abortion, and provides some useful
practical hints as to the best way to treat mares in order to prevent
them from " slipping foal." He remarks that the horse is a peculiarly
high-strung, nervous animal, and is easily affected by sudden changes
in its surroundings, especially during the breeding season. Such
changes are, no doubt, often responsible for setting up disturbances
in the nervous system, and so inducing abortion, more particularly
at that period of development at which the h'xation of the embryo
to the uterine wall is relatively insecure.

Abortion in cows is said to be commonest during the first month
of pregnancy. According to Wallace1 the usual causes are the
following : (1) Eating ergotised grass ; (2) injury due to horning by
other cattle, hunting by dogs, or shaking and bruising in travelling,
etc. ; (3) physical strain, resulting from walking over too soft land, etc. ;
(4) very cold or foul water, or frozen turnips, etc. ; (5) superpurgation,
whether occurring naturally or as a consequence of dosing by physic ;
(6) contagion from other cows affected by epidemic abortion. This is
said to be the commonest and at the same time the most dangerous
cause of abortion.

Bang 2 has shown that contagious, epidemic, or epizootic abortion
in cattle is due to a specific bacillus which he has been able to isolate
and cultivate in oxygenated glycerine-bouillon or serum-gelatine
agar. The germ causes the formation of a brownish-yellow exudate
between the chorion and the mucous membrane of the uterus, and
more particularly around the cotyledons, but the affected area may
be considerably greater.3 Bang has shown experimentally that the
germs may be carried to the seat of the disease by the blood after
intravascular injection, and furthermore, that they can be absorbed
through the alimentary canal. Thus, after administering some

1 Wallace (R), loc. cit. Wallace states that after abortion in cattle the
placenta adheres to the cotyledons, and should be removed artificially ; other-
wise it is liable to undergo a process of rotting, sometimes resulting in septicaemia
and death. See Fleming, Veterinary Obstetrics (Craig's Edit.), London, 1912.

2 Bang (B.), " Infectious Abortion in Cattle," Xat. Vet. 8oc., Liverpool,
25th July 1906.

3 Report of the Departmental Committee appointed by the Board of Agriculture
and Fisheries to inquire into Epizootic Abortion, London, 1909. According
to this Report, nothing more than a quite subsidiary role in the spread
of the disease can now be referred to the bull. For further information
and references see Surface, "The Diagnosis of Infectious Abortion in
Cattle," Report of Kentucky Exp. 8tat., 1912 ; " Notes on Infectious Abortion
in Cattle," Science, vol. xxxvi., 1912; and "Bovine Infectious Abortion
Epizootic among Guinea-Pigs," Jour, of Infectious Diseases, vol. xi., 1912 ; also
McFadyean, " Epizootic Abortion of Cattle," Jour. Comp. 1'ath. Ther., 1921.

FERTILITY 655

bouillon culture to a cow, the placenta was found covered with typical
exudate rich in bacilli. It is probable, therefore, that entrance
through the alimentary canal is the most frequent way by which the
disease is spread. There is some experimental evidence that cows
may acquire immunity to the disease, at least temporarily. Investiga-
tions show also that mares, sheep, goats, dogs, and guinea-pigs may
be infected with the bacillus experimentally, but in all probability
the disease is ordinarily confined to cattle. The abortion microbe
is stated to be oval or rod-shaped, between one and two microns in
length, and non-motile. It sometimes occurs singly, but in many
places the bacilli are collected in dense groups or colonies. The
microbe associated with abortion outbreaks in sheep is said to be a
vibrio and therefore totally different.1 It has been isolated and used
experimentally to infect pregnant ewes. Pregnant cows, however,
cannot be infected by it. Horses and swine may also suffer from
abortion of an epizootic nature.

The external use of antiseptics is said to prevent the spread of
contagious abortion by means of disinfection, 1 >ut isolation is the most
effective method.2 Vaccine treatment is an efficacious preventive.

The causes of abortion in sheep are dealt with at some length by
Heape in the paper already referred to.8 Statistical evidence shows
that an excessive proportion of shea'rling ewes in a flock is associated
with a relatively high percentage of abortion, and that ewes of
particular breeds in certain districts, or run on certain subsoils, are
more liable to abortion than the average for the breed in question.
Thus Lincoln sheep run on the Wolds suffer much more from abortion
than sheep of the same breed in other districts. The Southdown and
Hampshire Down statistics show that'a heavy rainfall during gestation
is associated with a high degree of abortion. Over-exertion (as from
jumping ditches), fright (from strange dogs or shooting), are usually
credited with producing abortion in sheep, but Heape remarks that
such causes are not truly responsible unless the ewes are in a
susceptible condition. The main conclusion reached is that the food
and the resulting condition of the ewes are the principal factors
which influence the percentage of abortion. Unsuitable food, causing
indigestion or other ailments, and poor food, resulting in bad nutrition,
are held to be mainly responsible. Heape states, however, that it is
not the kind of food so much as the condition of the food which is
most liable to be at fault, while the schedules show clearly that a poor
condition of ewes during gestation is associated with a relatively high

1 Heatley, "Abortion in Sheep," Board of Agric. Dcpt. Committee Report.
Printed by the Suffolk Sheep Society, Bury St. Edmunds, 1914.

2 Board of Agriculture Leaflet, No. 108, 1904.

3 Heape, " Abortion, Barrenness, and Fertility in Sheep," Jour. Royal Agric.
Soc., vol. x., 1899. See also Fleming, loc. cit.

656 THE PHYSIOLOGY OF REPRODUCTION

percentage of abortion. " Sheep-stained " pasture (i.e. pasture grown
with the aid of sheep manure or on which sheep have been run for
a considerable time previously) is credited with causing abortion, and
there is strong evidence in support of this view in cases where rank
or over-stimulated growth results.1

As already noted, the Dorset Horn and Lincoln breeds of sheep
suffer most from abortion.2 In the case of the former this may result
partly from in-breeding, since Dorset Horn ewes served by Hampshire
Down rams are less liable to " slip lamb " than those served by rams
of their own breed. It is possible, therefore, that the abortion may be
due to a want of vitality on the part of the developing embryo, the
cross-bred young possessing a superior vigour. Abortion among
Lincoln sheep has been known to reach thirty, forty, or even h'fty
per cent., and so to assume an epidemic form. Wortley Axe,3 who
reported on an outbreak of abortion among the Lincolnshire flocks in
the season of 1882-83, was disposed to attribute it to debility, arising
largely from foot-rot and exposure to cold winds and heavy continuous
rains, as well as to the feeding of the ewes on unripe, watery roots
and unwholesome, filth-laden shells. Heape has suggested that
abortion on the Wolds arises partly from the practice of unduly
crowding the ewes on turnip fields. As already mentioned, a bacillus
has been isolated from outbreaks" of abortion in ewes, and has been
used to infect other ewes for experimental purposes in the laboratory.

Hammond 4 has shown that atrophy of foetuses in utefo is a very
common phenomenon in pigs as well as in domestic rabbits. It occurs
at different degrees of embryonic development, and degenerate
fetuses of different sixes and in a mummified condition are commonly
found in the same uterus. Hammond counted the foetuses in the
uteri of twenty-two sows and found that for 100 eggs shed (shown
by the corpora lutea) there were 674 normal foetuses and 12*4
atrophic foetuses (leaving 20'2 ova missing or unaccounted for).
In domestic rabbits the proportion of degenerate foetuses was
closely similar. Degenerate foetuses in utero have been recorded
also for the following animals : mare, cow, sheep, goat, guinea-pig,
hamster, rat, mouse, ferret, dog, -cat, and rnole. The proportion of
atrophic foetuses in wild rabbits is very much smaller than in tame
ones, and Hammond draws the conclusion that the fertility of many

1 Abortion in sheep may result from more exceptional causes. Thus it is
recorded that a large proportion of a certain flock of Cheviot ewes slipped lamb
after a gale which blew down a number of Scotch fir trees, the abortion resulting,
in the owner's opinion, from the animals eating the branches and bark. See
Marshall, loc. cit.

2 Heape, loc. cit.

3 Wortley Axe, "Outbreak of Abortion and Premature Birth in the Ewe
Flocks of Lincolnshire during the Winter and Spring of 1882-83," Jour. Royal
Agric. »SW., vol. xxi., 1885.

4 Hammond, loc. tit., 1913 and 1921. These papers contain further
references.

FERTILITY 657

domestic animals is limited by the number of discharged and
fertilised ova which develop rather than by the number of ova
which are shed. With regard to the cause of the foetal atrophy
Hammond has shown that it is not due to bacterial infection
since the uteri are aseptic. He suggests that it may be brought
about by adiposity, by in-breeding, or by a genetic " lethal factor "
such as Kirkham l and others have shown probably to be the case
with the homozygous yellow mice which are never brought forth
alive but die in utero during implantation. The foetal atrophy is not
due to lack of room in the uterus, for this organ is capable of great
expansion, and the distribution of the degenerate foetuses is irregular
and does not suggest that death was due to overcrowding. It is
true, however, as Hammond has shown in pigs, that the size of the
foetus is roughly proportional to the extent of its membranes, and
that the foetal membranes of single lambs, which are as a rule larger
than twins, extend to both horns of the uterus. It is also generally
true that the average weight of the embryo increases as the size of
the litter decreases, and that the larger and better nourished the
mother the larger are the young. Nutrition is probably an important
factor both in the size of the litter and in the sizes of the individuals,
as experiments on various animals have shown, but there must be
variation in. the degrees of vitality inherent in the different foetuses.
Some perish more easily than others as is well shown in pigs, but
even those which survive long enough to be born are often ill-
nourished and under-sized and in striking contrast to other piglings
of the litter. Hammond states that atrophy of the foetuses begins
in the blood-vessels, which first become congested and then break
down. The foetal membranes may remain alive for some days after
the embryos have perished.

THE INCREASE OF FERTILITY, A PROBLEM OF PRACTICAL BREEDING

Heape 2 has shown from statistical evidence that the amount of
money invested in live stock in this country cannot be computed
at very much less than £450,000,000, and this sum does not include
the enormous capital spent on buildings, land, vehicles, and various
accessories. The annual export of live stock from Great Britain in
recent years has been tending steadily to increase, until it has
reached a total value of £1,750,000. It is clear, therefore, that
in this country the breeding industry occupies a position of no
inconsiderable importance, and that the scientific study of the
problems of breeding possesses a great national interest. Foremost

1 Kirkham, " The Fate of Homozygous Yellow Mice," Jour. Exp. Zool.
vol. xxviii., 1919. Lethal factors have been described for various other organisms
(Drosophila, maize, etc.). See Babcock and Clausen, loc. cit.

2 Heape, The Breeding Industry, Cambridge, 1906.

658 THE PHYSIOLOGY OF REPRODUCTION

among these problems is that which concerns itself with the factors
that control fertility.

Despite its comparative prosperity, it is evident that the 1 >reeding
industry suffers annually from no inappreciable loss. Allusion has
been made to the losses sustained by breeders owing to the occurrence
of abortion in domestic animals. Sterility, whether persistent or
temporary, is responsible for a greater reduction of profit. The
prevalent barrenness among the better class of Shire mares has
been already referred to, while incapacity to breed is perhaps still
commoner among Thoroughbreds. As already mentioned, the Royal
Commission on Horse- Breeding found that no less than forty per
cent, of the mares chosen for breeding in any given year failed to
produce offspring. Recent statistical evidence for heavy horses shows
an even larger proportion of mares failing to breed.1 Moreover,
there-is evidence that in certain districts of -India the percentage of
sterility is as high or higher than in this country.'2 Among cattle
the average loss from sterility and abortion (together with mortality
of calves) is estimated by Heape3 to be at least fifteen per cent.,
while it is shown in the report (already referred to) issued by the
Royal Agricultural Society on fertility in English sheep for the year
1899, that the proportion of sterile ewes was 4*71 per cent, out of
a total number of 96,520, and this percentage does not include the
ewes which aborted (see p. 651). In view of these facts, it is obvious,
as Heape has pointed out, that any means by which sterility in
domestic animals can be checked and their capacity to bear young
increased, must be possessed of great commercial value.

THE BIRTH-RATE IN MAN

It is now more than a century ago since Malthus4 advanced
his famous proposition that whereas population tends to increase
in geometrical ratio, the means of subsistence increase only in
arithmetical proportion. As a consequence of the acceptance of
that doctrine, the political economists of the early Victorian period
tended to see in over-population the most fruitful source of
pauperism, disease, and crime, and the cause of increasing congestion
in the future. That Malthus' predictions have not been verified is
a matter of common knowledge, and the problem before the modern
economist is not how to place a check on population generally, but
rather how to secure that future generations shall be sufficiently
recruited from that section of the population which is industrially
capable, while at the same time to prevent indiscriminate propagation.

1 Marshall and Crosland, "Sterility in Mares, with Recommendations to
Breeders of Heavy Horses," Jour, of the Board of Agric., vol. xxiv., 1918.

2 Ewart, loc. cit.

3 Heape, loc. cit.

4 Malthus, An Essay on the Principles of Population, 7th Edition, London, 1872.

FERTILITY 659

There is abundant evidence that in most civilised countries at
the present time the birth-rate (that is, the proportion of the
children born to the population) is tending to decrease, while in
some countries the actual population is diminishing. This decline
in the birth-rate has been made the subject of statistical inquiries
by Newsholme and Stevenson,1 and Udny Yule.2 These writers
have shown that the observed fall is not simply a consequence of
changes in the ages of the people, or in the proportion of married
to single women, for allowing for such alterations as have occurred,
the number of births per 100,000 of the population in England and
Wales, for example, has dropped from 32:56 in 1861 to 2729 in 1901.
Yule concludes that " the main factor in the fall of the birth-rate
has been a decrease in the fertility of married women: this fall has
been proceeding at an accelerating speed." 3

The decline in the birth-rate (so far as England and Wales are
concerned) is not appreciably greater in the towns than in the rural
districts. It is, however, especially marked in places inhabited by
the servant-keeping class.4 It appears to be greatest in those
sections of the population which give evidence of the exercise of
thrift and foresight, for Heron 5 has shown that the more cultured,
prosperous, and healthy classes are producing fewer children than
those belonging to a lower social status. Marriage fertility is on the
whole graduated continuously from a very low h'gure for the upper and
professional classes to a very much higher figure for unskilled labour.6

There is no direct evidence that this decline in the birth-rate is
due to an increase of sterility, for congenital unavoidable sterility
in either sex is rare. The inference has been drawn, therefore, that
the decline is principally the result of deliberate volition in the
regulation of the married state. Evidence that this inference is
correct is provided by the Fabian Society, whose report indicates
that the practice of limitation prevails with at least one-half, if
not three-fourths, of all the married people of Great Britain.
The statistics collected from other countries point in a . similar
direction. This is noticeably the case for New South Wales,

1 Newsholme and Stevenson, "The Decline of Human Fertility in the
United Kingdom, etc.," Jour. Royal Statis. Soc., 1906.

2 Yule, " On the Changes in the Marriage and Birth-Rates, etc.," Jour. Royal
Statis. Soc., 1906.

3 Yule, The Fall of the Birth-Rate, Cambridge, 1920. (With further references.)

4 Sidney Webb, TJic. Decline in the Birth-Rate, Fabian Soc. Tract, London, 1907.

5 Heron, "On the Eelation of Fertility in Man to Social Status, etc.,"
Drapers' Company Memoir, London, 1906.

6 The Population Problem, a Study in IJuman Evolution (Oxford, 1922),
is ably discussed by Carr-Saunders, who writes as follows : " It is forgotten
that the reduction in the birth-rate may be that which economic conditions
demand, and that it may of necessity have to begin with the upper classes.
Though, therefore, differential fertility by producing unfavourable germinal
changes is to that degree to be deplored, yet we have to remember that so far as
quantity is concerned, failure to meet economic requirements might be a much
greater misfortune."

660 THE PHYSIOLOGY OF REPRODUCTION

Victoria, and New Zealand among the British Colonies, and for
France among Continental nations. Indications pointing apparently
in the same direction are to be observed in the United States,
Germany (especially Saxony, and certain of the big cities), as well as
in Belgium and Italy. The German rural population are apparently
still unaffected, while the British and Irish Catholics are almost so,
since any regulation of the married state is forbidden by their
religion, but in other Catholic countries this prohibition does not
appear to be so strongly insisted on, and is often altogether ignored.
On the other hand, Udny Yule has shown that in some countries
(e.g. Belgium before 1875) the fall in the birth-rate began at a time
when artificial methods of contra-conception were not generally
practised, and his general conclusion is that the recent decrease has
not been effected mainly or solely by such a cause.1

To the political economist of seventy years ago the decline in
the production of children would have been regarded as the
fulfilment of an aspiration, but the modern economist takes a
different view. He believes that a mere limitation of numbers
cannot be a factor in the improvement of social conditions, and the
student of Eugenics never tires of urging that the real danger
before society is not over-multiplication, but multiplication of the
unfit. As Sidney Webb has said : " Modern civilisation is faced by
two awkward facts ; the production of children is rapidly declining
and this decline is not uniform, but characteristic of the more
prudent, foreseeing, and restrained members of the community. . . .
The question is whether we shall be able to turn round with
sufficient sharpness and in time. For we have unconsciously based
so much of our social policy — so many of our habits, traditions,
prejudices, and beliefs — on the assumption that the growth of
population is always to be reckoned with, and even feared, that a
genuine realisation of the contrary position will involve great
changes. There are thousands of men thinking themselves educated
citizens to-day to whose whole system of social and economic beliefs
the discovery will be as subversive as was that announced by
Copernicus. We may at last understand what the modern economist
means when he tells us that the most valuable of the year's crops, as
it is the most costly, is not the wheat harvest or the lambing, but
the year's quota of adolescent young men and women enlisted in the
productive service of the community ; and that the due proportion
and best possible care of. this particular product is of far greater
consequence to the nation, than any other of its occupations." 2

1 Yule, loc. cit. Pell has come to a similar conclusion, The Law of Births
and Deaths, London, 1921.

2 Sidney Webb, loc. cit. Cf. also Whetham, The Family and the Nation,
London, 1909 ; and Inge, Outspoken Essays, London, 1920.

CHAPTER XV
THE FACTORS WHICH DETERMINE SEX1

" What was a question once is a question still." — BACON.

A WORK upon the Physiology of Reproduction would be incomplete
without some reference to the problem of sex-determination, and
some account of the more recent attempts which have been made
towards its solution. The question has been dealt with at length
in several recent works, such as those by Morgan and by Doncaster,
Correns and Goldschinidt, and Goldschmidt,2 and the reader is
referred to these treatises, especially the last, for further references
and fuller information in regard to certain of the points discussed.
It is hoped, however, that the present summary may prove useful if
only as a supplement to the other volumes that have appeared,
since certain important papers dealing with sex-determination and
containing an account of experimental investigations have been
published since the appearance of the works referred to, and these
papers I have endeavoured to summarise here. Moreover, some of
the more recent observations, and more particularly those relating
to sex reversal, have necessitated a further revision of the conclusions
previously arrived at.

reproduction in organisms may occur by simple fission or
budding, in which case it is said to be asexual, or it may involve
the union of two conjugating cells, which in Metazoa and Metaphyta
are specially differentiated for the purpose, and are known as ova
and spermatozoa (see Child's work, p. 225, above). In some animals
these two types of cell are produced by the same individual, which
is then said to be hermaphrodite or monoecious, but such a condition
is rare or absent altogether among the highest forms of life. In
the vast majority of animals there are two sexes — that is to say,
two kinds of sexual individuals, the male and the female, whose

1 With additions by Cresswell Shearer.

2 Morgan, Heredity and Se.v, New York, 1913. Doncaster, The Determination
of Sex, Cambridge, 1914. Correns and Goldschmidt, Die Yererbung und Bestim-
mung des Geschlechts, Berlin, 1913. Goldschmidt, Mechanwmus und Physiologic
der Geschlechtsbestimmung, Berlin, 1920. See also Geddes and Thomson, The
Evolution of Se.r, Revised Edition, London, 1904 ; Thomson, Heredity, London,
1914 ; and Babcock and Clausen, Genetics in delation to Agriculture, New York,
1918.

662 THE PHYSIOLOGY OF REPRODUCTION

respective functions are to produce spermatozoa and ova. This
condition is described as dioscious. Again, in a relatively small
number of animals, of which the bee is a familiar example, there
are three kinds of individuals — perfect females, imperfect females,
and males. In a few insects there are even more than three kinds.
Lastly, in certain of the lower animals the females can reproduce
ova which are capable of developing into adult individuals without
conjugating with spermatozoa. This method of reproduction is
described as parthenogenetic (see p. 230).

Among dioecious animals the two sexual individuals are generally
produced in approximately equal numbers. Thus, in man the
number of male births is only slightly in excess of the number of
female births, the proportion varying very slightly in different
countries,1 while in those races in which the numerical proportion
of the two sexes among the adult population is very unequal,
inequality is due to a higher death-rate of children belonging to one
sex. Thus among the Todas the pronounced preponderance of males
over females results from the practice of female infanticide.2

Theories of sex determination may be conveniently arranged
under three headings : (1) Those in which it is assumed that the
sexual condition of the individual is determined subsequently to
fertilisation and during embryonic or larval life ; (2) those which
assume that sex is established either at the moment of fertilisation
or prior to fertilisation ; and (3) those which limit sex-determination
to no particular period, or which definitely assert that sex may be
established at different periods of development in different animals.

(1) THEORIES WHICH ASSUME THAT SEX-DETERMINATION TAKES
PLACE SUBSEQUENTLY TO FERTILISATION

In tadpoles sex is apparently indeterminate until a relatively
late stage of development, but it is said to be established at the
time of metamorphosis. Born,3 and subsequently Yung 4 and certain
other investigators, have adduced evidence in support of the view
that the sex is determined by the quantity and quality, of the food
supply. Thus they claimed that they could produce an excess of
females by feeding the tadpoles upon a meat or fish diet. The
conclusions of these authors, however, are hardly borne out by

1 Bodio, "Movimento della Populazione," Gonfronti Internazionali, 1895.

2 Punnett, "On the Proportion of the Sexes among the Todas," Proc. C<<i«l>.
Phil. Soc., vol. xii., 1904.

3 Born, " Experimentelle Untersuchungen ueber'die Entstehung der Gesch-
lechtsunterschiede," Brest auer drztliche Zeit., 1881.

4 Yung, " De 1'Influence de la Nature des Aliments sur la Sexualite," C. R.
de I'Acad. des Sciences, vol. xciii., 1881.

THE FACTORS WHICH DETERMINE SEX 663

more recent researches, for Cuenot's experiments,1 conducted on
similar lines to those of Born and Yung, show a preponderance
of males among tadpoles which were fed upon animal food, and
an approximate numerical equality among those which received an
exclusively vegetable diet. Moreover, the method adopted by Born
for ascertaining the sex of the individual tadpoles during the period
of metamorphosis seems to have been unsatisfactory, since it was
based on the assumption that the ovary is always larger than the
testicle, whereas this is not invariably the case. It is stated also
that frogs' eggs from certain localities yield a higher percentage of
females than those from other localities, and consequently that a
disproportion of the sexes may exist under normal conditions ; but
this fact in itself does not show that sex is not determined by
nutritive or other environmental influences, but may point to a
directly opposite conclusion. But, as Morgan points out, if the
natural disproportion between the two sexes is great, errors may
easily creep into the experimental results.2 Again, King's observa-
tions relating to sex-determination in Amphibians provide no
evidence that either food or temperature are factors in this process.3

Since the early work of Born and Yung, however, many other
observations of a more critical character have been made on the
question of sex-determination in Amphibians. The most remarkable
of these has been the recent work of Witschi.4 A full summary of
these observations down to the latter part of 1921 will be found in
Crew's 5 paper. It would seem that in the frog while the chromo-
some constitution may determine sex at fertilisation, in some
instances this is clearly overridden during subsequent development,
which results in the production of " somatic " males or masculinised
females. The mechanism by which the female is transformed is
one which acts through the internal secretions of the gonads.

Thus it would seem that in Amphibians sex is not definitely

1 Cutmot, "Sur la Determination du Sexe chez les Animaux," Bull, Sci. de
France et Belg., vol. xxxii., 1899.

- Morgan, Experimental Zoology, New York, 1907.

:i King, " Food as a Factor in the Determination of Sex in Amphibians,"
Biol. Bull., vol. xvi., 1909. "Temperature as a Factor, etc.," Biol. Bull.,
vol. xviii., 1910. See below, pp. 668-669 and pp. 692-693.

4 Witschi, " Der Hermaphrodismus der Frosches und seine Bedeutung fur
das Geschlechtsproblem und die Lehre von der inneren Sekretion der
Keimdrusen," Arch. f. Entivick., vol. xlix., 1921, also short paper in Am. Nat.,
1921. Witschi describes the frog as having an indifferent gland which might
develop either into an ovary or into a testis, but the latter is rare. Far more
individuals develop first ovaries which are later transformed into testes in the
larva. Oviducts grow in association with ovaries up to the time of transforma-
tion. Lateral herrnaphroditesiare not uncommon. (See footnote, p. 700.)

5 Crew, " Sex-Reversal in Frogs and Toads : A Review of the Recorded
Cases of Abnormality of the Reproductive System and an Account of a
Breeding Experiment," Jour, of Gen., vol. xi., 1921.

664

fixed at the time of fertilisation. In the case of the lamprey,
somewhat similar conclusions have been arrived at by Okkelberg1
in an important paper. In this animal the germ-cells of each germ
gland are seen at a very early stage to be of two kinds, one set
showing a tendency to divide rapidly, while the other shows a
tendency to grow, dividing very seldom. The former, he believes,
have a male, the latter a female, potentiality. The relative pro-
portion of anabolic and katabolic cells determines whether the
larva becomes <$ or <j>. The lamprey, like the frog, thus carries the
potentiality of both sexes, and its sex is not irrevocably 'fixed at
the time of fertilisation. Other cases of apparent sex-reversal are
considered in a later section of this chapter.

The experiments of Treat2 and other observers who attempted
to show that the sex of caterpillars could be determined artificially
by regulating the supply of food should perhaps be disregarded, as it
has since been shown that the sex in those animals is probably
established at the time of hatching. Furthermore, experiments by
Briggs 3 and other investigators have failed to support the hypothesis
that the proportion of the sexes can be altered by modifying the
diet, while Kellogg 4 has shown that with the silkworm moth, sex
is determined as early as immediately after the first larval moulting,
this conclusion being based on an examination of the rudimentary
reproductive glands.

According to Cuenot,5 the essential organs of reproduction in the
maggots of flies are not differentiated into ovaries or testicles until
a late period of larval development. It seemed possible, there-
fore, that in these animals the sex could be modified by the
conditions of nutriment or other external factors. Cuenot found,
however, that the proportion of the sexes was not materially affected
by the supply of nourishment, although the maggots were fed upon
different kinds of food, some being given brain, suet, and a little
meat, some a large supply of putrefying flesh, while others were
relatively starved.

Among bees and other hymenopterous insects the nutriment
appears to be the main factor determining the difference between the
two kinds of females (workers and queens). A worker larva can be
made to develop into a queen by supplying " royal food," that is, food
which is given to young queens. In the worker the female generative

1 Okkelberg, " The Early History of the Germ Cells in the Brook Lamprey,
Entospeuus Wuaeri (Gage), up to and including the period of Sex-differentiation,"
Jour, of Morph., vol. xxxv., 1921.

2 Treat, " Controlling Sex in Butterflies," American Naturalist, vol. vii., 1873.

3 Briggs, "Notes on the Influence of Food^n Determining the Sexes of
Insects," Trans. Entom. Soc., London, vol. i., 1871.

4 Kellogg, "Notes on Insect Bionomics," Jour, of Exp. Zoul., vol. i., 1904.

5 Cuenot, loc. cit.

THE FACTORS WHICH DETERMINE SEX 665

organs never fully develop, but royal diet stimulates these organs
to grow so that the larvae become queens. A partially developed
worker may be made partially fertile by supplying it with some of
the jelly obtained from a royal cell. The following table shows the
relative composition of the solid food given to workers and queens1: —

Solid Food.

Workers.

Queens.

1

Nitrogenous -

51-21

45-14

Fatty

6'84

13-55

Glucose

27-65

20-39

This table shows that the quantity of fatty material supplied to the
developing queens is very nearly double that given to the workers. .

There is no evidence that drone larvie can be converted into
females by a supply of royal or other food, so that the case of bees
can scarcely be regarded as affording a real instance of sex being
determined by conditions of nutrition, since workers are true females
whose reproductive organs and other sexual characteristics have
failed to develop owing to an insufficiency of stimulating food.

The case of white ants or termites is probably comparable, though
considerably more complicated, since the different kinds of sexual
individuals are more numerous. The young may develop into
workers, soldiers, or royal substitutes, and the latter may be further
transformed into fully fertile or " royal " individuals, while both
sexes (i.e. males and females) are represented in each of these forms.
Grassi's observations2 point strongly to the conclusion that these
different kinds of individuals are developed from similar eggs under
different conditions of nutrition which is supplied to the young by
the older members of the community ; but here again there is no
evidence that males can be converted into females or females into
males.

Ilolph 3 has described a series of observations on the production
of males and females in Ncmatns ventricostts, a species of sawfly.
These observations show that the percentage of females in broods of
larvae reared from fertilised ova steadily increased from June to
August and then proceeded to diminish. " We may conclude without
scruple, that the production of females from fertilised ova increases
with the temperature and with the food supply (Assimilationsleistung),

1 Geddes and Thomson, loc. cit.

2 Grassi and Sandias, "The Condition and Development of the Society of
Termites," Quar. Jour. Micr. Science, vols. xxxix. and xl., 1896-97.

:! Rolph, Biologische Probleme, Leipzig, 1884.

666 THE PHYSIOLOGY OF REPRODUCTION

and decreases as these diminish." l Certain further experiments with
unfertilised ova of the same species seem to show that " the more
abundant the metabolism (Stoffwechsel) and the nutrition, the
greater the tendency to the production of females." In the normal
condition males only were produced as a result of parthenogenetic
development, but the superior nutrition is believed to have led to the
production of females.

The fact that in certain Crustacea a condition of hermaphroditism
can be induced by an external cause acting on a sexually differentiated
individual is discussed below in dealing with latent characters, and
further observations of a comparable character and relating to
other animals are also considered.

(2) THEOEIES WHICH ASSUME THAT SEX - DETERMINATION TAKES
PLACE AT THE TIME OF FERTILISATION OR PREVIOUSLY TO
FERTILISATION.

Effect of Fertilisation. — While it seems certain that queen and
worker bees are developed from fertilised eggs under different
conditions of nutrition, the conclusion is now fairly established that
drones or male bees arise parthenogenetically from unfertilised eggs.
If this view is correct, it clearly follows that in bees the differentiation
into female and male individuals is brought about by the occurrence
or non-occurrence of fertilisation. This theory of sex-determination
in the bee was first formulated by Dzierzon,2 and has since been
accepted by Weismann3 and many other biologists, although some
writers, such as Beard,4 deny the conclusion that fertilisation is
capable of exercising any such influence.

In support of his contention Beard quotes an observation by
Weismann and Petrunkewitsch, showing that a drone egg may
occasionally undergo fertilisation. He also refers to the results
obtained by " bastardising " hives of bees through the introduction of
Italian queens into colonies of German workers and drones, or of
German queens into Italian swarms.5 In such a bastard hive Dzierzon
found a drone which appeared to be a cross between a German and
an Italian bee, and which consequently afforded evidence of a drone
egg having been fertilised. This result led Dzierzon temporarily to
doubt the truth of his hypothesis, but he subsequently accepted the

1 Translated by Geddes and Thomson.

2 Dzierzon, " Tiber die Befruchtung der Kb'nigin," Eichstadt Bicneii-Zeitung,
vol. i., 1845.

:! Weismann, "Ueber die Parthenogenese der Bienen," Anat. Anz., vol. v.,
1900.

4 Beard, "The Determination of Sex in Animal Development," Zool. Ja/irb.,
vol. xvi., 1902.

r> Von Siebold, Wahre Parthenogenesis bei Hchmetterlingen imd Bienen,
Leipzig, 1856.

THE FACTORS WHICH DETERMINE SEX 667

interpretation of von Siebold, who, suggested that the queen which
had given rise to the apparently bastard drone was herself of impure
descent, and that in reality the egg had not been fertilised. A
further exceptional case has been recorded by Perez,1 who found that
a considerable number of male bees produced by an Italian queen
which had been fertilised by a French drone appeared to be of mixed
blood. This result, which is admittedly unusual, has been explained
by Sanson2 as due to "reversion," and Morgan has pointed out
that the hybrid drones may conceivably have arisen from hybrid
workers which sometimes lay eggs, and further that male bees are
often very variable in their characters. Either of these explanations
would appear to be possible.

Moreover, the later observations of Petrunkewitsch,3 showing
that sperm nuclei are not found in drone eggs whereas they are
commonly met with in worker eggs, supply an important confirmation
of Dzierzon's hypothesis.

Attempts to extend this hypothesis to other hymenopterous
insects have not been so satisfactory, though it seems, as a general
rule, to hold good for ants. There are instances on record, however,
in which worker ants have developed from parthenogenetic ova, and
other exceptional cases have been stated to occur.4

Among the Tenthredinidee or sawflies also the unfertilised eggs
commonly develop into males, but this is by no means invariable.
Thus in some forms fertile parthenogenetic females only have been
known to arise for many generations in succession without the
appearance of males.5

In the parthenogenetic Rotifer, Hydatina, Maupas 6 has adduced
strong evidence that if the parthenogenetic male eggs are fertilised
they are thereby converted into " winter " eggs which give rise solely
to females. If this is so (and Maupas's conclusions are now generally
accepted), it is a clear instance of fertilisation altering the sex of

1 Perez, "Memoire sur la Ponte de 1'Abeille reine et la Theorie de
Dzierzon," Annales des Sciences Nat., vol. v., 1878.

2 Sanson, "Note sur la Parthenogenese chez les Abeilles," Annales des
Sciences Nat., vol. v., 1878.

3 Petrunkewitsch, " Die Richtungskorper und ihr Schicksal ini befruchteten
und unbefruchteten Bienenei," Zool. Jahrb., vol. xiv., 1901. "Das Schicksal
der Richtungskorper im Drohnenei," Zool. Jahrb., vol. xvii., 1902.

4 Wheeler, "The Origin of Female and AVorker Ants from the Eggs of
Parthenogenetic Workers," Science, vol. xviii., 1903.

5 Doncaster, " On the Maturation of the Unfertilised Egg and the Fate of
the Polar Bodies in the Tenthredinidce" (juar. Jour. Micr. Science, vol. xlix., 1906.

0 Maupas, " Sur la Multiplication et la Fecondation de 1'Hydatina senta,"
C. R. de rAcad. des Sci., vol. cxi., 1890. "Sur la F6condation de 1'Hydatina
senta," O. R. de f'Acad. des Sci., vol. cxi., 1890. "Sur la Determinisme de la
Sexualite chez Hydatina senta," C. R. de I' A cad. des Sci., vol. cxiii., 1891. Lenssen,
Contribution a 1*' Etude du Developpement, etc., chez 1'Hydatina, La Cellule,
vol. xv., 1898.

668 THE PHYSIOLOGY OF REPRODUCTION

the individual. It is stated, however, that impregnation has no
effect unless it is performed during the first few hours after-
hatching. Moreover, parthenogenetic female eggs are also produced.

In recent years a large number of further experiments have been
made with this rotifer by Whitney1 and also by Shull,2 in an
attempt to determine the conditions controlling sex-production.
Whitney has been able to change a pedigree stock of Hydatina senta
from a parthenogenetic female-producing variety, kept on Polytoma,
to a male-producing sexual stock by altering the diet to Ghl<n/u/-
domonas. This change, as Doncaster has pointed out, however, is
not a real sex change but rather a change from one mode of repro-
duction to another. The converse change could also be brought about.

Certain writers have adopted the view that sex in animals
generally is regulated by the time at which fertilisation takes place,
that is to say, by the condition of the germ-cells. Thus, Thury 3 and
subsequently Busing 4 expressed the opinion that an egg which is
fertilised shortly after ovulation usually develops into a female, and
that an older egg tends to produce a male. Thury claimed that he
could regulate the sexes in cattle by allowing coitus only at the
beginning or at the end of the oestrous periods, an early coitus being
supposed to result in the birth of a female, and a late coitus in the
production of a male.

Pearl and Parshley/' who have dealt with the matter statistically
in the cattle at the Maine Experiment Station, have found that as
the time of copulation approaches the end of the osstrous period,
there is a progressive increase in the proportion of male calves born.
They have thus confirmed Thury and Diising.

Pearl and Salaman0 have also investigated the question in man,
but found the evidence unsatisfactory.

Richard Hertwig,7 and later Kuschakewitsch, have carried out a
series of experiments on frogs, and these also show that over-ripeness
of the ova was associated with a preponderance of males, and in some

1 Whitney, "The Control of Sex by Food in Five Species of Eotifers,"
Jour, of E.rp. Zool., vol. xx., 1916.

2 Shull, " Relative Effectiveness of Food, Oxygen, and other Substances in
Causing or Preventing Male Production in Hydatina" Jour, of E.rp. Zool.,
vol. xxvi., 1918, and long series of papers on the same subject in the same
journal previous to this date. (See also below, p. 670.)

3 Thury, Ueber das Gesetz dfr Erzeugung der (Jesc.hlechter, Leipzig, 1863.

4 Diising, " Die Regulierung des Geschlechtsverhaltnisses bei der Vermeh-
rung, etc.," Jenaische Zeitsch., vol. xvii., 1884.

6 Pearl and Parshley, "Data on Sex-determination in Cattle," Biol. Bull.,
vol. xxiv., 1913.

6 Pearl and Salaman, " The Relative Time of the Fertilisation of the Ovum
and the Sex-ratio amongst Jews," Amer. Anthropologist, vol. xv., 1913.

7 Hertwig, " Ueber das Problem des sexuellen Differenzieurung," " Weitere
Untersuchungen, etc.," Verhaiull. Deutsch. Zool. (jes., vols. xv., xvi., and xvii.,
1905-06-07.

THE FACTORS WHICH DETERMINE SEX 669

cases even to the total exclusion of females. Kuschakewitsch l
showed that the results could not have been due to differential
mortality or differential fertilisation, and that seemingly, therefore,
the metabolic condition of the gametes must have been the cause of
the unusual proportions. King 2 also has shown that the sex-ratio
in toads can be affected by the metabolic condition of the eggs, as by
treating the eggs so as to reduce their water content more females
were produced, and by causing the eggs to absorb water more males
were produced.

Influence of Nutrition and Environment. — Schenk3 also has
elaborated a highly speculative theory which supposes sex to be
determined by the relative degree of " ripeness " or " unripeness " of
the ovum ; but the term " unripeness '' is here used to imply a
condition consequent upon incompleteness of nutrition, while
" ripeness " is held to result from a more favourable state of
nutrition. " Ripe " ova are supposed to develop into males, and
" unripe " ones »into females. The presence of sugar in the urine is
evidence of an incomplete metabolism, and hence is regarded by
Schenk as implying a condition likely to result in the birth of
females. By supplying women with a highly nitrogenous diet,
which prevented the elimination of sugar in the urine and made the
metabolism more complete, Schenk claimed that he could ripen
the ova, and so increase the chances of male offspring.

Cuenot4 has described some experiments upon rats, in which
some were fed mainly upon bread, and others were given an abundant
supply of different kinds of food. Schultze5 did some similar
experiments upon mice, but in neither case was there any evidence
of a preponderance of the sex among the young of the better
nourished individuals. (For Seller's work on Tala'poria, see p. 671.)

It has long been known that parthenogenesis is the normal
method of reproduction among plant-lice or Aphides during the
months of summer, successive generations of individuals arising in
this way, but that with the approach of autumn males make their
appearance, and reproduction then becomes sexual. If, however, the
Aphides be kept in an environment of artificial warmth, and at
the same time are supplied with abundant food, the succession of
parthenogenetic females may be caused to continue for years without
the appearance of the sexual form. It is to be noted that the sexual

1 Kuschakewitsch, Die EntwicJdungsgeschichte der Keimdriisen, etc., Festschr.
R. Hertwig, vol. ii., 1910.

2 King, " Studies on Sex-Determination in Amphibians," IV., Bwl. Bull.,
vol. xx., 1911. The other papers in this series should be consulted.

3 Schenk, The Determination of Seju, English Translation, London, 1898.

4 Cu6not, loc. eit.

5 Schultze, "Zur Frage von den geschlechts-bildenden Ursachen," Arch. f.
Mikr. Anat., vol. Ixiii., 1903.

6;o THE PHYSIOLOGY OF REPRODUCTION

and parthenogenetic females are not identical, and also that the
same female may give rise to parthenogenetic and sexual offspring, or
to males and females, or to only one sex. Moreover, Stevens has
shown that male and female embryos may be produced practically
simultaneously by the same individual. It is maintained, therefore,
by this writer that " the changes, in sex usually attributed to changes
in external conditions are really a change from the parthenogenetic
to the sexual mode of reproduction. The life cycle is often very
complicated, and in some species of Aphides there is evidence that
the environment (e.g. the trees on which they live) rather than the
temperature is responsible for the development of the sexual forms.1

Many of the lower Crustacea undergo a somewhat similar
alternation of generations. For example, the water-flea (Daphnia^,
after reproducing parthenogenetically during the summer time>
deposits eggs which give rise to sexual forms at the commencement
of autumn, and the female after impregnation lays the winter eggs
from which the new brood arises. This result is generally supposed
to be brought about by the conditions of temperature or nutrition.
But Weismann,2 as a consequence of numerous experiments and
observations, has cast doubts upon this view, believing rather that
the animal has been so constituted by natural selection that it tends
spontaneously to reproduce sexually in the appropriate season, and
that it does so to a large degree irrespectively of the actually
existing conditions. More recently Issakowitsch 3 has carried out an
investigation upon another daphnid, Simocephahis, from which he has
been able to show that differences in temperature may determine the
mode of reproduction, but that this result is effected indirectly by
the change of temperature altering the conditions of nutrition.
Unfavourable conditions tend to the production of sexual forms, and
favourable ones to the parthenogenetic method of generation. The
same individual female may give rise either to sexual or partheno-
genetic offspring, the conditions which exist in the -ovary appearing
to determine what kind of egg will develop.

In the Rotifer Hydatina senta there are at least two kinds of
females, which are distinguished by the kinds of eggs that they lay :
(1) thelytokous females, which produce other females partheno-
genetically, and (2) arrenotokous females, which produce males
parthenogenetically. The second kind of female may also produce
fertilised eggs. Furthermore, the thelytokous females may give rise

1 Balbiani, "Le Phylloxera du Chene et le Phylloxera de la Vigne, etc.,"
Mem. a UAcad. des Sri., vol. xxviii., 1884. Stevens, "Studies on the Germ Cells
of Aphides," Carnegie Institution (Washington) Publications, 1906.

2 Weismann, " Beitrage zur Naturgeschichte den Daphniden," Zeitsck.f. wiss.
Zoologie, vols. xxvii., xxviii., xxx., and xxxiii., 1876-79.

3 Issakowitsch, " Geschlechtsbestinmiende Ursachen bei den Daphiden," Biol.
Centralbl., vol. xxv., 1905.

THE FACTORS WHICH DETERMINE SEX 671

either to arrenotokous females or to more thelytokous females, and
the proportion of arrenotokous females so produced is liable to con-
siderable variation. Maupas l has sought to connect this variation
with differences in temperature, and Nussbaum2 with differences in
nutrition, but neither conclusion has been satisfactorily established.
The question has been reinvestigated by Punnett,3 who has carried
out a number of further experiments. In one of these a strain
which had hitherto appeared to be purely thelytokous was subjected
to considerable fluctuations of temperature. The rate of reproduction
was much retarded, but in the subsequent generations which were
produced no arrenotokous females could be found. Starvation
experiments were undertaken, and in these also thelytokous females
which had hitherto " bred true " continued to do so. Punnett
concludes that neither temperature nor nutrition has any influence
in determining the production of arrenotokous females. On the
contrary, it is the property of certain females to produce arrenotokous
females in a definite ratio, and the property of others to produce none.

Theories which assume that the Gametes are themselves Sexual. —
Many biologists have entertained the conception that the gametes
are themselves sexual, and a number of facts have been adduced
which give very strong support to this idea. Some of these have
already been mentioned, but probably the strongest evidence in favour
of this generalisation is that relating to the existence of special
sex chromosomes contained in the ova or spermatozoa.

Seiler4 has shown in Talceporia tubulosa that the direction in
which the maturation spindle turns during division determines
whether the sex chromosome remains in the egg or passes out in the
polar body.5 If it remains in, then the egg is male determined, and
if it passes out, female. The interest of his observations lies in the
evidence he has adduced that this condition can be experimentally
controlled by heat or cold. If the eggs are kept in the cold,
3° to 5° C., a higher proportion of females appear (ratio 155 ? to 100 <J),

1 Maupas, loc. cit. See also Lenssen, loc. cit.

3 Nussbaum, "Die Entstehung des Geschlechts bei Hydatitia senta," Arch,
f. Mikr. Anat., vol. xlix., 1897.

3 Punnett, " Sex-determination in Hydatina" Proc. Roy. /S'oc., B., vol. Ixxviii.,
1906.

4 Seiler (J.), " Das Verhalten der Geschlechtschromosomen bei Lepidopteren,"
Arch. f. Zellforsc/i., vol. xiii., 1914. "Geschlechtschromosomenuntersuchungen
an Psychiden," Zeitschr.f. ind. Abst. u. V&rerbungslehre, vol. xviii., 1917.

5 In this respect Morgan's observation on Phylloxera, (Jour, of Ejrp. Zool.,
vol. vii., 1909) should be recalled. It would seem that here the behaviour
of the sex chromosomes is controlled by some factor, for it can be seen in
certain oogonial divisions that one daughter cell (on account of its small size)
has already had its sex determined before the chromosomes have commenced
to draw apart and move into their respective daughter cells, so that the
chromosome complex of the daughter cells can hardly be claimed as the sex-
deterniining factor in this instance, but more properly as a sex resultant.

672 THE PHYSIOLOGY OF REPRODUCTION

the sex chromosome l passing into the polar body ; at a temperature of
35° to 37° C., however, fewer females appear (ratio 62 $ to 100 ^).
This work has been well reviewed by Goldschmidt.2

It has been known for a long time that two kinds of sperm exist
in the snail Paludina, a hair-like form and a worm-like form, but it
is commonly believed that only the former i,s functional. Dimorphic
spermatozoa have also been discovered in various other animals, but
the differences between the two kinds vary greatly .:i

Henking 4 made the discovery that in the bug, Pyrrhocoris, half
of the spermatozoa differ from the other half in possessing an
additional chromosome. M'Clung 5 was the first to suggest that the
difference between the two sorts of spermatozoa in this insect was
connected with sex-determination, and that those which contained
the accessory chromosome produced males, and that those without it
produced females. The last assumption has, however, proved to be
incorrect, since Wilson6 found that in this and other forms the
female and not the male contains an additional chromosome in its
somatic cells. It is almost certain also that the ova have one more
chromosome than one half of the sperms have, and the same number
as that possessed by the sperms which contain the additional chromo-
some. Consequently the latter are supposed to produce females, and
the former males.

For example, in Anasa tristis the somatic cells of the male contain
twenty-one chromosomes, whereas those of the female contain twenty-
two. Half of the spermatozoa are supposed to contain eleven
chromosomes, the other half having only ten. The ova are believed
to all resemble one another in containing eleven chromosomes. It is
concluded, therefore, that the spermatozoa possessing the smaller
number give rise to males, while those with eleven chromosomes
produce females.7

1 See below, p. 673.

2 Goldschmidt (R), Mechanismus und Pliysiologie der Gescklechtsbestimmung,
Berlin, 1920.

3 A list of species in which dimorphic forms of spermatozoa have been
recorded (down to 1902) is given by Beard, loc. cit.

4 Henking, " Untersuchungen ueber die ersten Entwicklungsvorgiinge in
den Eien der Insekten," Zeitsch. f. wiss. ZooL, vol. xlix., 1890, and vol. li., 1891.

5 M'Clung, "The Accessory Chromosome Sex Determinant," Biol. />>///.,
vol. iii., 1902.

6 Wilson (E. B.), " Studies on Chromosomes," Jour, of Exp. Zool., vols. ii.
and iii., 1905-06 ; vol. vi., 1909. " Note on the Chromosome Groups of Metapodiits
and Banusa" Biol. Bull., vol. xii., 1907. "The Supernumerary Chromosomes of
Hemiptera," Science, vol. xxvi., 1907. See also Stevens, "Studies in Speruiato-
genesis," Part I., 1905, and Part II., 1906, Carnegie Institution (Washington)
Publications. In these papers dimorphic spermatozoa (one kind containing
one smaller chromosome or lacking one chromosome) are described for various
species of Orthoptera, Coleoptera, Hemiptera, and Lepidoptera.

7 Foote and Strobell ("A Study of Chromosomes in the Spermatogenesis
of Anasa tristi#" Amer. Jour, of Anat., vol. vii., 1907), as a result of an investiga-

THE FACTORS WHICH DETERMINE SEX 673

Payne1 has recently shown that in Galgulus oculatus there are
two sorts of spermatozoa possessing respectively sixteen and nineteen
chromosomes, whereas the eggs are uniform in containing nineteen
chromosomes. Furthermore, the females are believed to have three
more chromosomes than the males (i.e. thirty-eight as compared with
thirty-five).

In another insect, Lygccus bicnicis, the male differs from the
female, not in having fewer chromosomes, but in the possession of a
pair of different sized chromosomes. The body-cells in the male
have twelve ordinary chromosomes and two sex chromosomes which
behave differently from the others. One of the sex chromosomes is
larger than the other, and has been called the X chromosome, the
second or smaller one being termed the Y chromosome.

After synapsis, or the pairing of the chromosomes preparatory
to spermatogeuesis, there are six double chromosomes, and the two
sex chromosomes, X and Y, which remain separated. At the first
maturation division all the chromosomes divide, the two resulting
cells each having eight chromosomes, including the X and Y. At the
second division, however, although all the other chromosomes divide,
the X and Y chromosomes do not divide, but each passes into a
separate product of division, that is, into a separate spermatozoon.
Each spermatozoon, therefore, contains six ordinary chromosomes and
either an X or a Y chromosome. In the female body-cells there are
twelve ordinary chromosomes and two sex chromosomes which are
similar, X and X. Preparatory to oogenesis there are seven double
chromosomes, the X's uniting together just as the other chromosomes
unite in pairs. The polar bodies are formed, and reduction occurs in
the usual way, each egg containing six ordinary chromosomes and
one X chromosome. The ova, therefore, are all similar, but those
fertilised by spermatozoa with X chromosomes become females, and
those fertilised by Y-bearing spermatozoa become males.2

The mode of sex inheritance displayed by Lyga'us is believed to
be characteristic of the very large class of organisms in which the
males are heterozygous as regards sex, and the females homozygous.8

tion with smear preparations instead of sections, find no evidence of a persisting
accessory chromosome in Ancua -tnttis, and believe that the body described as
such by Wilson is a plasmosome and not a chromosome.

1 Payne, " On the Sexual Differences in the Chromosome Groups in GaUndus
oculatus" Biol. Bull., vol. xiv., 1908. Correns also has shown that in some plants
there are two classes of male germ-cells, and that these are produced in equal
numbers (Die Bestimmung und Vererbu-ng dex Qeschlechtes notch nen/en Versucken
mit hoheren Pflanzen, Berlin, 1907).

2 Morgan, Heredity and >SV.r, New York, 1913.

3 The term heterozygote has been given by Bateson to offspring resulting
from the union of dissimilar gametes. Such organisms, according to the
Mendelian theory, produce more than one sort of gamete (see p. 200).
Homozygotes are formed by the union of similar gametes, and produce gametes

22

674 THE PHYSIOLOGY OF REPRODUCTION

Essentially the same mode of inheritance occurs in those insects
referred to above in which the male possesses a smaller number
of chromosomes than the female, but in which the presence
and peculiar nature of the sex chromosomes was not at first
recognised.

As regards the Y chromosome (using this term for the smaller
member of the pair in the male), it may be said that in some
organisms it is as large as the X chromosome, which is its mate;
in others it is smaller; while in others again it has disappeared
completely.

The mode of sex inheritance just described (called by Morgan
the XY type) is generalised in the following scheme : —

XX mating with XY

XX

The case of the bee, referred to above, in which females are
produced by fertilised eggs and males from unfertilised ones, belongs
almost certainly to this type of sex-inheritance, both functional
spermatozoa and ova containing one X chromosome. The fertilised
egg and female will then contain two X chromosomes; the un-
fertilised egg, containing only one X chromosome, becoming a
male.1

Bridges'2 work, however, has shown that in Drosophila, among
the offspring of triploid females, there are frequently a number of
individuals which are neither male nor female, but are sex inter-
mediates, being a mixture of both male and female characters.
These individuals Bridges has proved, both genetically and cyto-
logically, possess 2X chromosomes plus three sets of autosomes
(or ordinary chromosomes). Thus the old formula that " 2X equals
female" is seen to be inadequate, for here we have 2X chromo-
somes, yet they are not females. It would seem that they have

of one kind. Thus, homozygotes, as regards sex, are believed to produce
gametes bearing one sex character only (either male or female) ; whereas
heterozygotes, as regards sex, are supposed to give rise to both male-bearing
and female-bearing gametes.

1 It has been shown that the parthenogenetic gall-flies and phylloxerans may
also be brought into line with animals showing the typical XY mode of sex-
inheritance. Thus Morgan found that in Phylloxera, in which all the fertilised
ova become females, the " male " spermatozoa are rudimentary.

2 Bridges, " The Origin of Variation in Sexual and Sex-limited Characters,"
Amer. Nat., vol. Ivi., 1922.

THE FACTORS WHICH DETERMINE SEX 675

been shifted out of the female class by the presence of an extra
set of autosomes, and thus the autosomes are proved to play a
positive role in sex-production.

Again, Blakeslee1 finds in the jimson weed, Datura, many
mutations with a 2n, 3n, or even 4?i number of chromosomes. As
long, however, as they possess a balanced chromosome number, these
mutants are all remarkably stable and healthy, while all those
containing an unbalanced chromosome complex, such as a 2?i + l
condition, are very unstable, and frequently undersized and often
unhealthy in appearance. Thus while the 2n plant will be large
and vigorous in appearance, the 2?i + l individual will be half its size
and very unhealthy. The presence then of an extra chromosome
is capable of affecting the action of all the others. He comes to
the conclusion that a species on these grounds must be the result
of a whole series of more or less conflicting forces contained in the
individual chromosomes acting as a whole, and not the result of
any individual chromosome or number of chromosomes acting alone.
This conclusion accords with Bridges' work just mentioned, and
gives us a totally new conception of the action of the chromosome
in heredity.

The experimental study of the transmission of sex-linked
characters is in general accordance with the cytological evidence
as to sex-inheritance, an outline of which has been given above
Sex-linked characters are those which while ordinarily restricted
to one sex, may occasionally pass over to the other. Their
inheritance has been studied very fully by Morgan, in the fruit-
fly, Drosophila ampelophila, in which as many as fifty sex-linked
characters have been identified. In transmission they are supposed
to be located in the X chromosome.

Drosophila usually has red eyes, but Morgan found some males
with white eyes. When these latter were mated with red-eyed
females, the offspring had red eyes. The heterozygous red-eyed flies
when mated together gave rise to 2000 red-eyed females, 1000 red-
eyed males, and 800 white-eyed males. White-eyed males with
heterozygous red-eyed females gave rise to both red -eyed and
white-eyed males and females, the males and females being nearly
equal in number ; but the white-eyed individuals, as in the previous
mating, owing to less constitutional vigour, were fewer than the
red-eyed. White-eyed males and females gave rise exclusively to
white-eyed offspring, but red-eyed males of whatever origin when
mated with white-eyed females invariably gave rise only to red-eyed
females and white-eyed males.

1 Blakeslee, " Variation in Datura due to Changes in Chromosome Number,"
Amer. Nat., vol. Ivi., 1922.

676 THE PHYSIOLOGY OF REPRODUCTION

The results .are represented in the following scheme, where K
represents the red-eyed factor and w the white-eyed : —

(1) RR 9 x ww $ gave R«« <$ and K,w $.

(red) (white) (red) (red)

(2) Rw 9 x ~Rw <J gave R^tf £, ^vw <J, Rw 9, and RR 9.

(red) (red) ' (red) (white) (red) (red)

(3) Rw; 9 x ww $ gave Rw <£, ww; ^, Rw 9> and ww $.

(red) (white) (red) (white) (red) (white)

(4) ww 9 x Rw ^ gave tvw £ and Rw 9.
(white) (red) (white) (red)

(5) ivw 9 x ww (J gave ww ^ and ww $ .
(white) (white) (white) (white)

These results are to be explained on the assumption that the
red-eyed male produces two sorts of spermatozoa, male-producing
and female-producing, and that whereas the female - producing
spermatozoa carry the factor for red eyes, the male-producing ones
do not. This conclusion has received cytological confirmation in the
discovery of Miss Stevens x that the male Drosophila has a pair of
unequal chromosomes, and Morgan naturally assumes that the larger
or X chromosome carries the sex-linked characters.

Doncaster had previously found in the currant moth, Abraxas
grossulariata, a condition of things which is the precise converse of
what Morgan has established for Drosophila. He showed that in
with this insect there is a rare variety, which generally occurs only
in the female sex. This variety, which is called A. grossulariata
lacticolor, is a Mendelian recessive, so that when crossed with an
ordinary grossidariata male, the offspring are all typical, the lacticolor
variety disappearing. Experimental crossings yielded the following
results :—

(1) Lact. 9 x gross. £ gave males and females all gross.

(2) Heterozygous 9 x heterozygous J gave gross. ^, gross. $,

and lact. ?.

(3) Lact. $ x heterozygous ^ gave all four possible forms

(gross. c£, lact. ^, gross. $, and lact. $), the lacticolor males
being the first ever seen.

(4) Heterozygous $ x lact. ^ gave gross. ^ and lact. $.

(5) Lact. 9 x lact. $ gave lact. ^ and lact. $.

(6) Wild gross. 9 x lact. $ gave gross. ^ and lact. ?.

It is shown, therefore, that males of the lacticolor variety can be
produced by mating lacticolor females with heterozygous males (i.e.
with males obtained by crossing the two original varieties, and so
presumably bearing two sorts of gametes), but that the converse

1 Stevens, "A Study of the Germ Cells of Certain Diptera," Jour. Exp. Zool.,
vol. v., 1908.

THE FACTORS WHICH DETERMINE SEX 677

mating (4) results in offspring which are either grossulariata males
or laeticolor females. Furthermore, whereas lacticolor females
mated with wild grossulariata males (1) produce offspring which
are of both sexes, but all of the grossulariata variety, the converse
cross (6) yields grossulariata males and lacticolor females. It is
concluded, therefore, that the wild and presumably pure grossulariata
females are heterozygous for sex, femaleness being dominant and
maleness a homozygous recessive character. All the females are
believed to produce male-bearing and female-bearing gametes in
equal, numbers, whereas all the males appear to produce only one
sort of spermatozoon. In confirmation of this conclusion Doncaster
since discovered a pair of unequal chromosomes in the female
Abraxas, corresponding therefore with the X and Y chromosomes of
the other insects described.

The results obtained by Miss Durham in her experiments on
cinnamon canaries are explicable on a similar hypothesis. When a
cinnamon male was mated with a green female, the female offspring
were cinnamon and the males green ; but when a cinnamon female
was paired with a green male, all the offspring of both sexes were
green.1 Where, however, a green cock of the second generation (the
Fj generation produced by crossing) was mated with a cinnamon
hen, both green and cinnamon birds of both sexes were produced ;
but when a green cock of the second (Fa) generation was crossed
with a green hen the resulting male birds were all green, but the
females were of both types. A more complex case of a like kind
has been brought to light by Bateson and Punnett in their investiga-
tion on the heredity of the black pigmentation of the silky fowl in
its crosses with brown Leghorns and other fowls with light shanks.
Here two allelomorphic characters, in addition to the two sex
determinants, are concerned, but Bateson and Punnett state that
the facts point very clearly to some such solution as that indicated
by Doncaster's experiments with Abraxas. A clearer case is that
of the factor for barring in the Barred Plymouth Rock. If a barred
cock is mated with an unbarred hen (Cornish Indian G'ame) all
the chicks of both sexes are barred ; if a barred hen is mated
with an unbarred cock, all the males are barred and all the
females unbarred.2 Similar results have been obtained with
other breeds.3

The mode of sex-inheritance shown by Abraxas and the other

1 Durham, Report to the Evolution Committee of the Royal Society, IV., London,
1908.

2 Pearl and Surface, " On the Inheritance of the Barred Pattern in Poultry,"
Arch. f. Entwick.-Mech., vol. xxx., 1910. The sex-linked factor for high egg-
production has been already mentioned (p. 644).

3 See Doncaster, The Determination of Sex, Cambridge, 1914.

678 THE PHYSIOLOGY OF REPRODUCTION

animals cited has been called by Morgan the WZ type. It is
represented diagrammatically as follows : —

WZ mating with

The females are heterozygous for sex, and the males homozygou
that is to say, there are two sorts of ova but one sort of spermatozoon.

This type of sex-inheritance appears to be characteristic of
Lepidoptera and birds, while the XY type occurs in other insects, in
Myriapods and spiders, in Xematodes, and among Vertebrates in all
Mammals and probably also in fishes and Amphibians.1

Parkes,2 as a result of an ingenious research on numerical sex-
inequality in man, has arrived at very clear conclusions in support
of the view that the male is heterozygous and the female homozygous
for the sex-determinant. He examined many dozens of genealogies,
and of these found six to be abnormal in having a proportion of
more than 1100 males to 1000 females. The total number of
individuals was 1792, of which 1001 were males and 791 were
females. When the female lines were separated from the male the
following results were obtained : —

Male lines - 1167 : males, 685; females, 482.

Female lines 625 : „ 316; „ 309.

It was thus found that the excessive male-bearing tendency
was vested exclusively in the male line, which indicates that the
spermatozoa carry the sex-determinant, and that the abnormal
ratio is not accounted for by selective fertilisation.

It has been shown, however, that with some animals, whereas
a certain chromosome constitution is undoubtedly usually correlated
with a particular sex, it cannot be regarded as the efficient cause of
that sex, since it may under special conditions be overridden, and
the alternative sex produced (see pp. 663 and 693).

1 King states that only one X chromosome occurs in the male of the
Amphibian, Necturus (Anat. Record, vol. vi., 1912). Among Mammals Wodsedalek
has found two sorts of sperms in the horse and pig. The numbers of somatic
chromosomes are : horse, 6 36, 9 38 ; pig, 6 18, 9 20 (Biol. Bull., vols. xxv.,
xxvii, and xxx., 1913-14-17). In man there is some dispute about the numbers
of chromosomes, but according to von Winiwarter there are forty-seven in the
male and forty-eight in the female (Arch, de Biol., vol. xxvii., 1912). (See p. 168.)

2 Parkes, "Sex-Heredity, with Special Reference to Abnormal Numerical
Inequality between the Sexes," Science Progress, vol. xv., (April) 1921.

679

The view that sex is determined entirely by the ova had been
put forward some time previously by Beard, who stated that in the
skate, Raja batis, there were two kinds of eggs — one large, which
gave rise to females, and another small, which produced males. He
pointed out that there were two sizes of eggs in Hydatina senta,
Phylloxera, and Dinopkilus apatris as well as in other animals, and
that these were related to sexual differences.

It is also pointed out in support of Beard's view that according
to von Ihering1 embryos which are found in one chorion (and which
are supposed, therefore, to have arisen from one ovum) in the
Edentate Praopus hybridus, are invariably of one sex, and that
" double monsters " in man are of the same sex, while Marchal 2
states that in the chalcid fly (Ageniaspis fuscicollis), in which a
chain of embryos takes origin from a single egg, these embryos are
all of one sex.

The view has also been entertained that there is a relation
between the position of the ovary and the sex of the ova. Thus,
according to Rumley Dawson,3 the ova produced by the right ovary
become males, and those produced by the left become females. This
theory is believed to be applicable especially to man, and is based on
clinical evidence and on a supposed alternation of the sexes of the
eggs discharged at the ovulation periods. It clearly cannot apply
to birds, in which the left ovary only is functional, and King 4 has
shown experimentally that it is inapplicable to Amphibians. The
theory as well as the alternative one that sex depends on the
position of the testis from which the fertilising spermatozoon
was derived has been negatived by Copeman5 as a result of an
experimental investigation upon rats.

Heape 6 has expressed the belief that " each ovum and sperma-
tozoon in the generative glands contains within itself sex, which is
probably determined by the laws of heredity, but that the proportion
of those male and female ova and spermatozoa which are developed
and set free from the generative glands may be regulated by
selective action, exerted in accordance with the resultant of a variety

1 Von Ihering, " Ueber Generations- wechsel bei Saugethieren," Biol.
Centralbl., vol. vi., 1886. Newman, The Biology of Twins, Chicago, 1917.

2 Marchal, " Eecherches sur la Biologic et le Developpement des Hymenop-
teres parasites," Arch, de la Zool. Exper. et Gen., vol. ii., 1904.

3 Dawson, The Causation of Sex, London, 1909.

4 King, "Studies on Sex Determination in Amphibians," Biol. Bull., vol. xvi.,
1909.

5 Copeman, "Sex-Determination," Phys. So<:., May 1908 (unpublished).
The results were eventually published in abstract in Proc. Zool. Soc., 1919,
which contains further suggestive information. See also Doncaster and
Marshall, Jour, of Genetics, vol. i., 1910 ; and King, Jour, of Exp. Zool., vol. x.,
1911.

6 Heape, " Note on the Proportion of the Sexes in Dogs," Proc. Camb. Phil.
Soc., vol. xiv., 1907.

68o THE PHYSIOLOGY OF REPRODUCTION

of extraneous forces. If this be true, the proportion of living male
and female ova and spermatozoa which are freed from the generative
glands, and the proportion of the sexes of the offspring which result
therefrom, will thus be influenced."

Heape is of opinion, however, that just as there is evidence that
adult animals are never purely male or female,1 so it is probable
that the sexual products (i.e. the gametes) are themselves similarly
constituted. According to this view, an ovuin or a spermatozoon
may possess dominant male or female characters as the case may
be, and recessive characters of the opposite sex. " In such cases
the possibility of infinite gradations of sexual differentiation in an
individual would be vastly increased, and from the point of view of
heredity, such complex conditions carry with them factors of the
highest importance."

Ova and spermatozoa in which the characters of one sex are
dominant are referred to as being male and female, and Castle's
conclusion 2 that an ovum of one sex must always be fertilised by a
spermatozoon of the opposite sex is adopted, but whether the sex of
the adult is determined by the ovum or by the spermatozoon is a
question which is left open, as it may admit of a different answer for
different species of animals, or even for different individuals. Heape
says, however, that even if that be so, the sex of the ovum must be
regarded as bearing a regular relation to the sex of the embryo as
surely as if it conferred its own sex.

" On this assumption a female parent producing ova of one sex
only will give birth to embryos of one sex, unless the male parent
possesses no spermatozoa of the opposite sex wherewith to fertilise it,
in which case the union will be barren. Dtising3 claimed that the
statistical results he obtained from a study of the mating of
Thoroughbred horses indicated the dominant influence of the male
parent on the sex of the offspring. Any sire that usually produces
spermatozoa of one sex only can be fertile, as a rule, only with mares
which produce ova of the other sex, and to such an extent he
determines the proportion of the sexes of the offspring for which he
is responsible. But where the sperm of both sexes is uniformly
produced, the sire must be fertile with all mares producing ova, and
as only one ovum is produced by each mare, the responsibility for
the sex of the offspring then lies solely with the female parent."

The opinion is expressed that much of the evidence cited to show
the dominating influence of the male parent on the offspring produced

1 Evidence on this point, including some of that adduced by Heape, is cited
below in dealing with heriaaphroditism and the latency of sexual characters.

- Castle, "The Heredity of Sex," Bv.U. Museum Compt. ZooL, Harvard,
vol. xl, 1903.

:! Diising, (oc. cit.

THE FACTORS WHICH DETERMINE SEX 68 1

may be explained on this view: "While statistically the father
might be shown to be responsible, physiologically the mother
controls the governing influence."

It is assumed that in normal cases both sexes of ova and
spermatozoa are probably produced in the gonads in equal quantities,
and that in those females which shed all their ova the proportion
of the sexes in the offspring is, in all likelihood, determined by
Mendelian laws. But it is pointed out that in many animals only a
small proportion of the ova formed in the ovary ever reach maturity,
the remainder undergoing degeneration and ultimately absorption
(see p. 151). It is inferred, therefore, that the proportion of the
sexes among the ova which survive and are discharged must depend
directly upon the causes which lead to the degeneration of some
ovarian ova and the continued development of others. On this view
it is held that the ova are subject to the same law of natural
selection as other organisms, and that in some cases the male ova
are best fitted to survive, and in other cases the female ones.

Heape1 has shown further that in the ovary of the rabbit two
kinds of degeneration prevail, and that in one kind it is the follicle
which first begins to undergo atretic changes, and that in the other
kind it is the ovum that is earliest affected. The former condition
is regarded as evidence that the available supply of nutriment is
insufficient for the maintenance of all the ova in the ovary, while
the latter is interpreted to mean that the ovum, for one reason or
another, is unable to assimilate the nutriment provided for it. It is
possible, therefore, that nutrition may in this way exercise a selective
action as regards sex. In this connection it is interesting to note
that, according to Issakowitsch,2 the nutritive conditions prevailing
in the ovary of the daphnid Simocephalus are determinative as to
the kind of egg which will develop (i.e. whether it will be a partheno-
genetic or a " winter " egg), and that the two kinds of eggs are stated
to arise in different parts of the ovary. Moreover, Heape suggests
that the marked difference between the death-rate of men and women
during famines,3 for example, may be reproduced among male and
female ova in the ovary when that organ is subjected to conditions
of a homologous kind.

Heape's general conclusions are summarised as follows : —

"(1) That through the medium of nutrition supplied to the ovary,
either by the quantity or by the quality of that nutrition, either by
its direct effect upon the ovarian ova or by its indirect effect, a
variation in the proportion of the sexes of the ova produced, and

1 Heape, " Ovulation and Degeneration of Ova in the Babbit," Proc. Roy. 8oc.,
B., vol. Ixxvi., 1905.

2 Issakowitsch, loc. cit.

3 M'lvor, Madras Census Reports, 1883.

22 A

682 THE PHYSIOLOGY OF REPRODUCTION

therefore of the young born, is effected in all animals in which the
ripening of the ovarian ova is subject to selective action ;

"(2) That when no selective action occurs in the ovary the
proportion of the sexes of ovarian ova produced is governed by laws
of heredity."

Having arrived at these conclusions, Heape next adduces evidence
that certain external forces may affect the proportion of the sexes in
dogs. It is shown that amongst greyhounds, conception during the
period from August to November is most favourable to the production
of males under the conditions of breeding at present practised, and
this result is attributed to a selective action on the ova produced at this
time. There is evidence also that among dachshunds and Basset
hounds the seasons affect the proportions of the males and females
born. The bloodhound returns seem to show that an excessive
production of males is associated with in-breeding. Further, there is
statistical evidence that a higher proportion of males is produced in
the larger litters, that the larger dogs produce the larger litters, and
consequently that the larger breeds have a racial tendency to produce
an excess of dog pups. Lastly, the schedule returns strongly support
the popular belief that there is a tendency to prolonged gestation
when the embryo is of the male sex.

In a further paper 1 Heape discusses the apparent influence of
extraneous forces on the proportion of the sexes in two aviaries
of canaries, kept under different conditions. One aviary was
kept at a regular temperature during the breeding season; it was
comparatively well lighted, and the sun had access to it. On the
other hand, the birds did not receive specially rich nutrition.
The other aviary was kept in a room facing north and east, and the
temperature was allowed to vary considerably during the breeding
time, but the birds were always fed with a plentiful supply of
rich food. In the former of the two cases nesting, hatching, and
moulting took place earlier, only about half the percentage of loss
was experienced, and from the nests in which all the eggs were
hatched, the percentage of males produced was more than three
times that which was obtained from the other aviary, in which
the environmental conditions were less favourable. The results
obtained in each case could not be ascribed to the particular strains
of canaries, since an interchange of birds between the aviaries was
not followed by any material alteration in the proportion of the
sexes in the two environments. It is concluded, therefore, that
the ova were subject to a selective action on which depended the
proportional differences produced.

1 Heape, " Note on the Influence of Extraneous Forces upon the Proportion
of the Sexes Produced by Canaries," Proc. Camb. Phil. Soc., vol. xiv., 1907.

THE FACTORS WHICH DETERMINE SEX 683

"As a rule in nature the climatic forces which stimulate the
activity of the generative functions are also associated with a
plentiful supply of food; the conditions which excite the one
ensure the supply of the other. Among domesticated animals
living in the open air, on the other hand, any forcing of the breeding
time is brought about by special feeding. In neither case are the
results obtained comparable to those we have now before us, where
both the quality and the quantity of the food supplied is regulated
entirely independently of the other causes which stimulate the
activity of the generative system. It is to this peculiar combination
'I attribute the regularity of the remarkable differences shown in
these aviaries."

In a still later paper1 Heape shows that there is evidence of
the influence of extraneous forces upon the proportion of the sexes
produced by the white and coloured peoples of Cuba. Illegitimate
unions were found to give rise to a larger proportion of females, and
it is concluded that in this class of union there is an exceptionally
active metabolism of the mother which favourably affects the
development of those ovarian ova which give rise to female offspring.

Heape suggests further that much of the evidence that has been
collected in regard to the influence of nutrition and other environ-
mental causes upon the proportions of the sexes, although it may
be disregarded from the point of view from which it was put forward
(since it is commonly assumed that the conditions directly determine
the sex of the embryo), may yet be well worthy of attention from
the standpoint adopted by him. Some of this evidence is briefly
referred to below.

(:3) THEORIES WHICH LIMIT SEX-DETERMINATION TO NO PARTICULAR
PERIOD OF DEVELOPMENT, OR WHICH ASSERT THAT SEX MAY
BE ESTABLISHED AT DIFFERENT PERIODS.

Influence of Age of Parent. — Hofacker2 and Sadler3 arrived
independently at the conclusion that the sex of the offspring depends
on the relative ages of the parents — that when the father is the
oldest more male births occur, and similarly when the mother is
the oldest there tends to be a preponderance of females. This
hypothesis, which is known as Hofacker and Sadler's Law, has been
both confirmed and contradicted,4 but the most recent statistical

1 Heape, " The Proportion of the Sexes Produced by Whites and Coloured
Peoples in Cuba," Phil. Trans., B., vol. cc., 1909.

2 Hofacker, Ueber die Eigenschaften ivelche sick bei Menschen wnd Thieren auf
die Nachkommen vererben, Tubingen, 1828.

3 Sadler, The Law of Population, London, 1830.

4 Geddes and Thomson, loc. cit.

684 THE PHYSIOLOGY OF REPRODUCTION

investigation l on the causes controlling sex in man lends no support
to it. Moreover, Schultze's experimental investigation 2 on the sexes
produced by mice of different ages has led likewise to a negative
result.3

Copeman and Parsons,4 however, found that does aged over six
months produced more males than does under that age, but in
view of the evidence in favour of male heterozygosis as regards sex
among Mammals recorded above, little stress can be laid upon such
observations.

Influence of Parental Vigour or Superiority. — Considerable
importance has been attached by breeders and others, and notably
by Starkweather,5 to the comparative vigour or condition of the
parents as a factor in sex-determination. According to Starkweather,
the superior parent tends to produce the opposite sex. This theory
has been accepted by Allison,6 who believes it to be applicable to
Thoroughbred horses. It is obvious, however, that in attempting
to apply Starkweather's hypothesis, much depends on the signification
to be attached to the term " superiority," and for this, if for no other
reason, the theory is unsatisfactory. Furthermore, Schultze7 has
shown that long-continued or strained reproduction in female mice
has no effect on the proportion of the sexes produced. The results
of experiments on the effects of in-breeding were also indefinite or
contradictory.

Influence of Nourishment. — Of the various external factors which
have been supposed to have direct influence in determining sex,
nourishment seems to have found more favour than any other. In
some cases this factor is supposed to act upon the developing embryo
or larva (see p. 662), and so to determine its sex, while in other cases
it is concluded that sex is established at an earlier period.

Geddes and Thomson have elaborated the idea that favourable
nutritive conditions tend towards the production of females, and

1 Newcomb, "A Statistical Inquiry into the Probability of Causes of the
Production of Sex in Human Offspring," Carnegie Institution (Washington)
Publications, 1904. Newcomb states that the first-born child of any mother
is more likely to be a boy in the proportion of about eight to seven.

2 Schultze, "Zur Frage von den geschlechts-bildenden Ursachen," Arch. f.
Mikr. Anat., vol. Ixiii., 1903.

3 This theory, and that which follows, should possibly be included among
those which assume that sex is settled at fertilisation ; for if sex is determined
by the age of the parents, it seems to follow that no event occurring during
embryonic life can alter it. This point, however, does not appear to have been
raised by the authors of the theory.

4 Copeman and Parsons, " Observations on the Sex of Mice," Proc. Roy. Soc.,
vol. Ixxiii., 1904. For other observations of a similar kind see Goldschmidt,
loc. cit., where full references may be found.

5 Starkweather, The Law of Sex, London, 1883.

6 Allison, The British Thoroughbred Horse, London, 1901.

7 Schultze, loc. cit.

THE FACTORS WHICH DETERMINE SEX 685

unfavourable ones towards the development of males, and certain of
the evidence referred to above (p. 662) has been cited by them in
support of this hypothesis. The normal female metabolism is said
to be relatively anabolic, while the greater activity of the male is
held to indicate a preponderance of katabolic conditions. Conse-
quently the generalisation is reached that abundant or rich nutrition
(or any other favourable circumstance) tends to induce an anabolic
habit, and so favours the development of females; and conversely,
that deficiency of the necessary food supply (or any adverse
circumstance) leads to a katabolic condition of life, and so causes
the production of males. According to this idea, the organism is
at first "sexually indifferent," the sex becoming established at
varying periods of development in different animals according to
the circumstances. Thomson has subsequently admitted that some of
the evidence which was formerly adduced in support of this view
has been invalidated, since in a very large number of animals sex
appears to be fixed in the fertilised ovum or earlier, and con-
sequently subsequent conditions of nutrition ordinarily play no
part in determining the relative proportion of males and females.
But Thomson is still disposed to lay stress on the connection
between sex and metabolism, believing that the determinants for
each of the sexual characteristics (both male and female) are present
in all ova and in all sperms, and that their liberation or latency
depends on a bias towards egg- production or sperm-production.
The so-called contrasted peculiarities of the two sexes are due in
certain cases "to internal physiological conditions which give the
same primordium two different expressions, much less different than
they seem." l

Riddle2 has elaborated a theory of sex- determination which is
somewhat similar to that of Geddes and Thomson ; but Riddle's
view is based on experimental evidence obtained from a prolonged
study of sex-phenomena in doves and pigeons. This investigator
interprets sexual differentiation as the expression of quantitative
differences in the rate of protoplasmic activity, the more active
metabolism being associated with a production of males, and the
less active with females. The theory is elaborately worked out, and
it is shown that much of the accumulated evidence on this question
supports (e.g. see above, p. 668) the view that the preponderance of

1 Thomson, Heredity, London, 1908.

2 Riddle, " The Determination of Sex and its Experimental Control," Bull.
Aimer. Acad. Med., vol. xv., 1914. "Sex-control and Known Correlations in
Pigeons," Amer. Nat., vol. 1., 1916. "A Quantitative Basis of Sex, etc.," Science,
vol. xxxix., 1914. " The Theory of Sex, etc.," Science, vol. xlvi., 1917. " A Note
on Social Aspects of New Data on the Biology of Sex," Jour. National Inst. of
Social Sciences, 1915. See also Jennings, Riddle, and Castle, Lectures on Heredity,
Washington, 1917.

686 THE PHYSIOLOGY OF REPRODUCTION

male or female characteristics is conditioned by the level or rate
of the metabolic processes. Large size of yolk, a low percentage of
water in the yolk, a high percentage of stored material and a high
total of stored energy, and an exhausted physical condition or
advanced age in the mother are all associated with a low level of
metabolism and with the female sex.

The work on pigeons and doves was begun by the late Professor
Whitman, and continued after his death by Riddle, who confirmed
and extended Whitman's original results. They showed that with
crosses the percentage of males increases with the width of the cross
until sterility is reached. Since males are characterised by a more
active metabolism, the results are in agreement with the commonly
observed superior vigour of hybrids. By overworking the birds,
that is to say, by not allowing them to nest their own eggs and
forcing them to continue laying eggs in rapid succession, the first
several pairs of eggs laid in the spring produced all or nearly all
males, whereas the last several pairs of eggs laid in the autumn gave
rise almost or quite exclusively to females, while both sexes were
produced in the summer or transition period. These results are in
correlation with the fact that the developmental energy is greatest
early in the season, and then declines, so that Whitman found that
at the extreme end of the season the eggs were unable to hatch
at all.

The possibility of assortative mating and differential death-rates
are fully considered and rejected. Thus hens which when crossed
throw all males will, when mated to birds of their own kind, produce
both sexes equally. Moreover, the eggs are of two kinds, large and
small, and these in the wild pigeon are normally associated with
females and males respectively, but in the crossing experiments the
birds utilise " female-producing " ova for the formation of males, and
vice versa, the eggs thus changing their original sexes.

Furthermore, Riddle finds grades of sexual individuals, some
females being more masculine than others, and some males coming
to resemble females, and if ovarian extracts are injected into the
more masculine females, and extracts of testis into the more feminine
ones, the sex-behaviour of the birds may be very largely reversed,
but the effect is not permanent.

Lastly, the sex of the birds could not only be changed ; it could
also be accentuated. The hens hatched from the second clutch laid
in the autumn by overworked pigeons were found to be even more
pronouncedly female than normal birds, inasmuch as the right ovary
which usually atrophies, in these circumstances persists.

Needless to say, Riddle rejects the chromosome theory as an
explanation of how sex is determined, and in support of his con-

THE FACTORS WHICH DETERMINE SEX 687

tention there is other evidence, as will be shown later, that although
a certain chromosome constitution, like a secondary sexual character
in an adult, is usually correlated with one sex, this constitution may,
under certain conditions, be overridden and the other sex develop.

Statistical Investigations on Man. — Statistics of human births
have been brought forward in support of the view that the
proportion of the sexes varies with the conditions of nutrition. It
has been pointed out that in France the proportion of births of boys
and girls is 104'5 to 100 for the upper classes (who are presumably
best nourished), and 115 to 100 for the lower classes (who are more
poorly fed). In the " Almanack of Gotha " the proportion recorded is
105 boys to 100 girls, while for Russian peasants this proportion
is 114 to 100. Among the nobility of Sweden statistics show a
proportion of 98 male to 100 female births, but that given for the
Swedish clergy is 108P6 boys to 100 girls.1 There is therefore some
slight evidence that the percentage of female births is a little higher
among -those classes which are best nourished or subject to more
favourable circumstances, but the differences are very small.

Punnett2 has examined the statistics collected in the official
census of the county of London for the year 1901, with a view to
determining the relative proportions of the sexes amongst different
classes of society. The following is his summary and conclusion : —

" If the population of London be divided into three portions
exhibiting graduated poverty, it is found that the proportion of male
to female infants produced [or rather which have survived] is lowest
in the poorest portion, highest in the wealthiest portion, and inter-
mediate in the intermediate portion. The proportion of males is
highest of all in a number of births taken from ' Burke's Peerage,'
where the nutrition may be supposed to be of the best. From this
alternative conclusions may be drawn : that either more favourable
conditions of nutrition (1) may result in a large proportion of male
births [a conclusion which is contrary to that indicated in the returns
mentioned above, but which nevertheless appears to be warranted at
first sight], or (2) may have no effect on the proportion of the sexes,
or (3) may even result in a relative preponderance of female births,
but that in the last two cases the effect is masked by other factors
which affect unequally the different strata of society. Such factors
are shown to exist in a differential infant mortality, a differential
birth-rate, and probably also in a differential marriage-age. These
factors all tend to diminish the proportion of males in the poorer
portions of the population, and consequently render the first of the

1 See Morgan, loc. cit.

- Punnett, " On Nutrition and Sex-Determination in Man," Proc. Camb. Phil.
. Soc., vol. xii., 1903.

688 THE PHYSIOLOGY OF REPRODUCTION

above alternative conclusions improbable. Whether the second or
third of the other possible conclusions is to be accepted must remain
doubtful so long as we are not in a position to estimate the quantitative
effect of the factors given above. From the necessarily rough estimate
which he has been able to form, the writer's opinion is that their
combined effect would not be sufficiently great to mask a pre-
ponderance of female births due to better nutrition, and consequently
he is inclined to believe that in man, at any rate, the determination
of sex is independent of parental nutrition. In any case its influence
can be but small."

Newcomb,1 as a result of an investigation into the statistics of
multiple births, has come to the conclusion that sex is established at
different periods of development in different cases. He shows that
there is a tendency among human offspring for twins to be of the
same sex, a fact which he regards as supplying a "practically
conclusive negation of the theory of completely determined sex in
the original germs." His conclusion appears to be that sex is
established by " accidental causes," the nature of which is at present
unknown, and that in the case of twins the sex-determining factors
act similarly on both children, and so tend towards a uniformity of
sex. But he omits to mention the probability that some twin
embryos arise from a single ovum, a fact which would account for
their sexual identity on the assumption that sex is already determined
in the germ-cell.

HERMAPHRODITISM AND SEXUAL LATENCY

Organisms which combine within themselves the essential
characters of both sexes are said to be hermaphrodite. True
hermaphrodites produce both ova and spermatozoa, but there are all
gradations between true and partial hermaphroditism (in which the
essential organs of reproduction are not involved), and between the
latter and the completely unisexual condition, in which the characters
of the other sex are either latent or absent altogether.

Complete hermaphroditism is the normal state in many groups of
invertebrate animals (many sponges, coelenterates, and worms, and
some molluscs and crustaceans). In some forms the male and female
sexual elements do not exist contemporaneously, but are called forth
separately by different environmental conditions or are associated
with particular phases in the reproductive cycle (see Chapter I.).
In such cases the fact that the animal is hermaphrodite is liable to
be obscured.

Among vertebrate aiiimals true hermaphroditism is rare, though

1 Newcomb, loc. cit.

THE F-ACTORS WHICH DETERMINE SEX 689

its casual occurrence has been recorded even in Mammalia, and is
said to be comparatively frequent in certain species of Amphibia.1

According to Castle 2 the true hermaphrodite is a sex mosaic, the
alternative sexual characters existing side by side without dominance
of either, and passing (without segregation) into the gametes.
Dioecious individuals are supposed to result ordinarily from a union
of gametes in which one sex is dominant and the other recessive, so
that no one individual is purely either male or female. The occurrence
of partial hermaphroditism may be held to be an expression of an
incomplete dominance of the characters of one sex.

Partial hermaphroditism is usually said to occur when only one
kind of gonad is developed (either testis or ovary) in conjunction
with accessory generative organs characteristic of both sexes. Such
cases are by no means uncommon even among the higher animals.
The so-called " Free-Martins " among cattle have been held to be
examples of incomplete hermaphroditism.3

Among animals which are usually regarded as purely dioecious
there are many instances of vestigial or even of functional sexual

1 See Geddes and Thomson, loc. cit. Curtis, " Studies on the Physiology of
Reproduction in the Domestic Fowl " (Biol. Bull., vol. xvii., 1909). Pearl and
Surface have described a case of an hermaphrodite fowl which had a testis
on one side and an ovary on the other. The accessory organs were likewise
unilaterally arranged. Externally it was an antero-posterior gynandromorph,
having male characters in front but female body characters. Cf. Weber's
chaffinch (p. 337) and Poll's bullfinch, which were lateral gynandroniorphs.
Such gynandroniorphs are not uncommon among some insects (Hymenoptera).
See also Shattock and Seligmann's papers quoted on p. 341, and Bateson and
Thomas, " Note on a Pheasant showing Abnormal Sex Characters," Jour, of
Genetics, vol. vi., 1917. For an account of the question of hermaphroditism in
man, with a discussion of the evidence, see von Neugebaur, Hermaphroditismus
beim Menschen, Leipzig, 1908, and Gudernatsch, " Hermaphroditismus Verus in
Man," Amer. Jour, of Anat., vol. xi., 1911. The latter author states that there
is no clear case of true hermaphroditism in man or any mammal.

2 Castle, loc. cit.

3 Lillie's interpretation of the Free-Martin is referred to below (p. 695).
According to Berry Hart, however, the Free-Martin is in reality a sterile bull
which is co-twin of a noraial fertile bull (" The Structure of the Reproductive
Organs of the Free-Martin, with a Theory of the Significance of the Abnor-
mality," Proc. Roy. Soc. Edin., vol. xxx., 1910). The Free-Martin has also
been regarded as a sterile cow born co-twin with a potent bull. In most cases
a vagina and rudimentary uterus have been described, but vesiculse seminales
and other male organs are also stated commonly to occur. Berry Hart bases
his explanation of the occurrence of Free-Martins upon his theory of sex
(Menddian Action on Differentiated Sex, Edinburgh, 1909). According to this
theory, sex is determined by a " sex-gamete " which may be either male or
female. Them are also male and female " non-sex gametes," which unite with
the " sex-gametes " but are non-potent in determining sex. A female sex-
gamete uniting with a male non-sex gamete gives rise to a female zygote,
and conversely. Moreover, according to Hart, a Free-Martin with a potent
bull twin is the result of a division of a male zygote, so that the somatic
determinants are equally divided, but the gametic determinants unequally
divided, the potent going to the one twin, the potent bull, and the non-potent
to the Free-Martin. It has been shown, however, by Lillie that the twins arise
from two separate ova.

690 THE PHYSIOLOGY OF REPRODUCTION

organs characteristic of one sex being present normally in individuals
of the opposite sex. The mammary glands and teats of the male
mammal and the clitoris of the female are examples of such organs.
A more striking case is that of the pipe-fish (Siphostoma floridcr), in
which the male possesses a marsupium which acts functionally as a
placenta.1

In the great crested grebe the positions assumed during pairing
by the two sexes are interchangeable, for the .male may adopt the
passive attitude and the female the active one.2 Keversal of pairing
positions has also been described in moor hens and in tame pigeons.
Here we have an instance of the reversal of an instinct.

Weininger 3 has elaborated the idea that just as there may be an
" Idioplasm " that is the bearer of the specific characters, whether
morphological, physiological, or psychological, and exists in all the
cells of a multicellular animal, so also there may be two sexual modes
in which this idioplasm can appear, namely an " Arrhenoplasm " or
male plasm, and a " Thelyplasm " or female plasm. He maintained
further that every metazoon cell (and not merely every reproductive
cell) has a sexuality lying somewhere between arrhenoplasm and
thelyplasm, but that the actual degree of maleness or femaleness
varies in the different groups of cells of which the animal is built up.
Moreover, the different parts of the organism were supposed to possess
their own sexual determinants, which were believed to be stable
from their earliest embryonic foundation. Weininger made no
suggestion as to what it is that determines the differentiation of the
original protoplasm into arrhenoplasm and thelyplasm, but his idea,
though somewhat too morphologically conceived, is useful if only
because it emphasises the fact that male and female characters coexist
(though they are very unequally represented) in most if not in all
dioecious individuals — that is to say, that such individuals are rarely,
if ever, wholly male or wholly female. " There may be conceived,"
he wrote, " for every cell all conditions, from complete masculinity
through stages of diminishing masculinity to its complete absence
and the consequent presence of uniform femininity."

Weininger drew special attention to the gradations in sexual
characters which exist among men and women. There are many
men, he remarks, with a poor growth of beard and a weak muscular
development, who are otherwise typically males ; and so also there

1 Gudger, " The Breeding Habits and the Segmentation of the Egg of the
Pipe-Fish, Siphostoma floridce," Proc. U.S. Nat. Jfus., vol. xxix., 1905.

2 Julian Huxley, " The Courtship Habits of the Great Crested Grebe,:i Proc.
Zool. Soc., 1914. Huxley discusses the significance of the process, of which he
gives a detailed account. References are given to papers by Selous (
1901-02), also describing reversed pairing in the grebe and other birds.

3 Weininger, Sex and Character, English Translation, London, 1906.

THE FACTORS WHICH DETERMINE SEX 691

are women with ill-developed breasts who in other respects are
typical females. There exist all transitional forms from the most
masculine male to the most effeminate male, and on the other side,
from the sapphist and the virago to the most feminine female ; but
in man the characters of one sex are always dominant, though the
degree of dominance varies through considerable limits. On this
view, the phenomena of so-called sexual inversion and homosexuality,
which are ordinarily regarded as purely pathological, are in reality
psychological manifestations of special characters belonging to the
recessive sex.1

Such cases as those cited above have led Castle, Heape, and others
to conclude that all animals and plants are potentially hermaphrodite,
inasmuch as they contain the characters of both sexes, although
ordinarily the characters of one sex only are developed, while those
of the other are either latent or imperfectly developed.

Castle has cited cases from among plants in which the characters
of one sex can be induced to appear by the artificial destruction of
those of the other. Examples of the same kind of phenomenon are
supplied by certain animals. Thus Potts2 has shown that in the
male Hermit Crab ova make their appearance in the testes, and the
secondary sexual characters become modified in the direction of the
female as a consequence of the animal being affected by the parasite
Peltogaster. Similar changes occur in a number of other animals
belonging to widely different groups, but they are especially common
in the Crustacea. Geoffrey Smith, who has paid considerable attention
to this subject,3 explained the phenomenon by assuming that the
males, in order to cope with the drain on the system caused by the
parasites, have to increase their vegetative activity, and that they do
this by suppressing their male organisations and calling into play the
female ones, which they possess in a latent condition.

In a later paper on the sex - metabolism of Inachus, Smith
suggested that in the male affected by Sacculina the assumption of
female characters is due to the formation of a yolk-forming substance
(or female generative substance) similar to that normally elaborated

1 For further information see Krafft-Ebing, Psychopathia Sexualis, Stuttgart,
1882; Havelocfc Ellis, Studies in the Psychology of Sex: Sexual Inversion,
Philadelphia, 1901 ; Forel, The Sexual Question, English Translation, London,
1908 ; and Bloch, The Sexual Life of our Time, English Translation, London,
1908. For a discussion on the distinctions between men and women, see
Manouvrier, " Conclusions gen6rales sur 1'Anthropologie des Sexes et Applica-
tions sociales," Rev. de UEcole d ' Anthropologie de Paris, 1909 ; Havelock Ellis,
Man and Woman, 5th Edition, London, 1914, and Bucura, Geschlechtsuntersehiede
beim Menschen, eine Klinisch-physiologische Studie, Wien, 1913.

2 Potts, "The Modification of the Sexual Characters of the Hermit Crab,
etc.," Quar. Jour..Micr. Science, vol. 1., 1906. (See p. 326, Chapter IX.)

3 Smith (G.), "Sex in the Crustacea, etc.," British Association, Report,
Leicester Meeting, 1907 ; " Studies in the Experimental Analysis of Sex," Quar.
Jour. Micr. Science, vols. liv. and lv., 1910.

692 THE PHYSIOLOGY OF REPRODUCTION

in the ovaries, and that this so alters the general nutritive conditions
in the direction of the female' sex that eventually ova are formed in
the gonad. On this view the yolk substance is produced in response
to a stimulus set up by the parasite.

Braem1 has described an experiment in which he divided into
two parts a mature female of Ophryotrocha puerilis. After some weeks
the head portion regenerated and produced spermatozoa, but the ova
almost disappeared. There was no sign of hermaphroditism at the
outset, and Braem regards the case as one of change of sex resulting
from the altered conditions.

Orton z states that in the mollusc Crepidula fornicata the males
under certain conditions may change into females, thus showing that
they have the potentialities of both sexes. The life history of this
mollusc has been further investigated by Gould,3 who shows that
the free swimming young, after settling upon older individuals, pass
through a series of sexual changes. First they pass through a
neutral phase, next they develop into males ; then they change
into hermaphrodites, and lastly become females. In Crepidula piano,
the individuals only become males if attached at or near a larger
individual; otherwise they become females without any transition
from the neutral condition.

The marine annelid Bonellia displays similar phenomena. The
larvae, after being free swimming, become attached to the sea bottom
and develop through a neutral phase into females, or else they establish
themselves upon the proboscis of a mature female and become males.
Baltzer,4 by releasing such larvae before their sex had become com-
pletely established and forcing them to lead an independent life,
was able to produce grades of intersexual individuals, in which the
degrees of maleness or femaleness depended upon the duration of
time on which they had been attached before being released.

Potts5 has adduced evidence that in certain hermaphrodite
Nematodes, in Rhabdocoal Turbellarians and in Rhizocephala the
monoecious condition has arisen through the spermatozoa developing
in the ovaries in gradually increasing numbers in successive generations.

Champy 6 has described some interesting experiments on newts,

1 Braem, " Ueber die Aenderung des Geschlechts durch aussere Beeinflussung,
etc.," Anat. Anz., vol. xxxiii., 1908.

2 Orton, " On the Occurrence of Protandric Hermaphroditism in the Mollusc
Crepidula fornicata," Proc. Roy. >S'oc., B., vol. Ixxxi., 1909.

3 Gould, "Studies on Sex in the Hermaphrodite Mollusc Crepidula plana,"
Jour, of Exp. Zool., I., II., and III., vol. xxiii., 1917, and vol. xxix., 1919.

4 Baltzer, " Die Bestimmung des Geschlechts nebst einez Analyse des
Geschlechtsdimorphismus bei Bonellia," MM. Zool. Stat. Neapol., vol. xxii., 1914.

6 Potts, " Notes on the Free-living Nematodes," I., Quar. Jour. Micr. Science,
vol. lv., 1910.

6 Champy, "Changement experimentelle du Sexe chez le Triton alpestris"
C. R. de VAcad. Sci., vol. clxxii., (9th May) 1921. (See also footnote, p. 700.)

THE FACTORS WHICH DETERMINE SEX 693

(Triton alpestris). He found that if the males were starved severely
at a time when spermatogenesis should be active, the development of
the secondary sexual characters was arrested, the animals remaining
more or less " neuter," as in winter. In the following spring the
testes were seen to be replaced by bands of fatty tissue, and the
secondary characters did not appear. Two such males which were
abundantly fed in the next winter partially assumed the coloration
of the female. One was dissected on llth January, and contained
only the fatty bodies which had replaced the testes. Another was
kept until 8th April, by which time it had become entirely female in
appearance. Each fatty body now contained an ovary with odcytes,
and there was also an oviduct on either side. Moreover, it fostered
the fertile eggs of a female with which it had paired some time before.

Crew1 has described a number of frogs with abnormal repro-
ductive systems, and adduced evidence that these, or some of these,
were chromosomally females (XX in composition) which, instead of
developing into normal females, became transformed into " somatic "
males by the action of some factor or combination of factors which
had overridden the chromosome constitution. He points out that
the mating of such individuals, functioning as males, must disturb
the sex-ratio of the next generation, and that such an interpretation
may explain the unusual sex-ratios recorded by various observers.

Julian Huxley2 had already suggested such a possibility, and
applied it statistically to the case of the " millions fish " (Girardinus
pceeiloides) for which the sex-ratio had been found to be abnormal,
those bred in the Zoological Gardens, as recorded by Boulenger,
being produced in the ratio 3 $ : 1 $, but subsequently changing to
2 $? : 3 <$, and then later to 1 $ : $, which last ratio continued for some
years and as long as the fish were bred at the Gardens. Huxley
has shown that these abnormal ratios can be explained on the
assumption of an overriding of the chromosome constitution by
means of external influences, the theory as applied to this special
case being worked out in some detail.

Boring and Pearl3 have described hermaphrodite fowls with
gonads and external characters as well as sex behaviour in process

. * Crew, " A Description of Certain Abnormalities of the Reproductive Organs
found in Frogs, etc.," Proc. Roy. Physiol. Soc. Edin., vol. xx., 1921. See above,
p. 663, where the work of Witschi, etc., is referred to ; also footnote, p. 700.

2 Huxley, "Note on Alternating Preponderance of Males and Females in
Fish and its Possible Significance," Jour, of Genetics, vol. x., 1920. See also
" Recent Advances in the Biological Theory of Sex," Jour. Roy. Soc. of Arts,
vol. Ixx., (January and February) 1922.

3 Boring and Pearl, "Sex Studies," XI., Jour, of Exp. Zool., vol. xxv., 1918.
The authors say that the amount of luteal tissue in the ovary is precisely
correlated with the degree of external somatic femaleness. Elsewhere they
record luteal cells in the testes of hen-feathered males. See also Crew, Vet.
Jour., vol. Ixxix., 1922.

694 THE PHYSIOLOGY OF REPRODUCTION

of changing from a female to a male condition. The ovaries failed
to reach complete development, but discharged follicles and luteal
cells as well as fully formed spermatozoa are described.

Bond l has given an account of a Formosan pheasant with unilateral
development of the secondary male characters and an ovo-testis on
the left side, and this bird he is disposed to interpret as having de-
veloped from a female zygote in which the sex-factor divided unevenly.

Eiddle's experiments on sex-reversal in pigeons and doves have
already been referred to, and it was recorded that this investigator
obtained various grades of sexual individuals ranging from complete
males to complete females, in some of which the sex characteristics
might be over-emphasised as by the development of a right oviduct.

Intersexual forms have been described in various insects and
notably by Goldschmidt2 for the gypsy moth Lymantria. He
crossed two species of this moth, L. dispar and L. japonica, both of
which are strongly sexually dimorphic, and showed that with
suitable combinations of different races of these species " intersexes "
forming a continuous series passing from complete maleness to
complete femaleness could be produced. The results are ascribed
to different degrees of potency in the sex-factors, and thus a strictly
genetic interpretation was arrived at, but Goldschmidt's latest
results with sex-ratios, as Huxley remarks, indicate the probability
of moths with the chromosome constitution of one sex having been
changed into functional individuals of the other sex.

Huxley refers also to Harrison's3 results with another species
of moth, and to Keilin and Nuttall's 4 account of a graded series of
intersexual lice, as well as to the experiments of Hertwig and
others, and the records of Pearl and Parshley above mentioned, all
of which point in the same direction.6

It has already been mentioned that the Free-Martin has been
regarded as a partial hermaphrodite. Lillie 6 has shown that during

1 Bond, " On a Case of Unilateral Development of Secondary Male Characters
in a Pheasant, etc.," Jour, of Genetics, vol. iv., 1914.

2 Goldschmidt, " Experimental Intersexuality and the Sex Problem," Amer.
Nat., vol. 1., 1916. For a full account with references to many papers, see
Goldschmidt's book referred to above, p. 661.

3 Harrison, "Genetical Studies in the Moths of the Geometrid Genus Oporabia,
etc.," Jour, of Genetics, vol. ix., 1919.

4 Keili n and Nuttall, " Hermaphroditism and other Abnormalities in Pediculus
humanus" Parasitology, vol. xi., 1919.

5 See also Banta, " Sex Intergrades in a Species of Crustacea (Simocephalus)"
Proc. Nat. Acad. Sci., vol. ii., 1916. Sturtevant, "Intersexes in Drosophila,"
Science, vol. li., 1920. Sexton and Huxley, " Intersexes in Gammarus, etc.,"
Jour, of Marine Biol. Assoc., vol. xii., 1921 ; and Bridges, loc. cit. (see p. 674).

0 Lillie (F.), "The Theory of the Free-Martin," Science, vol. xliii., 1916;
" Sex-Determination and Sex-Differentiation in Mammals," Proc. Nat. Med. Sci.,
vol. iii., 1917 ; "The Free-Martin : A Study of the Action of Sex-Hormones,"
Jour. E.vp. Zool., vol. xxiii., 1917.

THE FACTORS WHICH DETERMINE SEX 695

development the vessels of the chorion of the sterile twin anastomose
with those of its fellow, which becomes a fertile bull, and that sexual
differentiation in the male precedes that of the female. Consequently
the male twin exerts an influence over the reproductive system of
its fellow at an early stage when the female organs are still un-
developed, and it does this through an internal secretion which is
present in the common circulating medium. The growth of the
generative organs is thereby partly inhibited in the female twin,
while the vestigial male structures are stimulated so as to undergo
some development. The Free-Martin, therefore, is an intersexual
individual wrhose development is due to the influence of a hormone
elaborated in the male twin, and carried thence to its fellow through
a common circulatory system.

The fact that the embryos arise from different eggs and not from
one, as had been previously suggested, is shown by the presence of
two corpora lutea in the ovaries. Assuming Lillie's theory to be
correct there is no apparent reason, as Huxley has pointed out, why
the ovarian internal secretion of the mother should not penetrate
to the fostuses in any mammal and so produce intersexual individuals,
and one can only suppose that there is some special protective
mechanism to prevent this from occurring.1

Minoura,2 by removing a portion of the shell from the eggs of
fowls during the second week of incubation and transplanting on
to the chorio-allantoic membrane a piece of gonad from another
individual, has succeeded in producing artificial "Free-Martins"
showing varying grades of intersexuality. The grafts were obtained
from both other chicks and older birds but the effects were similar.
Minoura found that in female-type embryos the right gonad, which
normally atrophies, might be got to persist as a result of an ovarian
graft.

• Hammond,3 after describing a partially hermaphrodite pig, ex-
presses the view that the development of the accessory genital organs
in such cases is under the control of the gonad, which was for the
time being better developed or more potent. A similar explanation
has been suggested by Stone 4 to account for a comparable condition
in a goat.

The experiments on sex-reversal by Steinach, Lipschiitz, Pezard,

1 For an account of the "Structures and Homologies of the Free-Martin
Gonads," see Willier, Jour, of Exp. Zool., vol. xxxiii., 1921.

- Minoura, " A Study of Testis and Ovary Grafts on the Hen's Egg, etc.,"
Jour, of Exp. Zool., vol. xxxiii., 1921.

3 Hammond, " A Case of Hermaphroditism in the Pig," Jour, of Anat. and
Physiol., vol. xlvi., 1912. Cf. Crew, Vet. Jour., vol. Ixxviii., 1921.

4 Stone, "A Typical Male Sex-ensemble in the Domestic Goat," China
. Mvd. Jour., (November) 1920. Many other such cases are known.

696

THE PHYSIOLOGY OF REPRODUCTION

and Sand have been described in an earlier chapter. Sand l has
recently demonstrated the effects of simultaneous transplantation
of a testis and an ovary in an infantile castrated guinea-pig and

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the grafting of ovaries into the testes of rats or guinea-pigs, and
has shown that hermaphrodites with a decided bisexualism of the

1 Sand, "Experiments on the Internal Secretion of the Sexual Glands,
especially on Experimental Hermaphroditism," Jour, of P/iysiol., vol. liii., 1919.

THE FACTORS WHICH DETERMINE SEX 697

psycho-sexual character could be produced, associated with growth
of the mammae on the one hand and some development of the male
organs on the other.

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Moore,1 working upon rats and guinea-pigs, has obtained results
in a general way similar. Like Sand, he has produced artificial

1 Moore (A.), " On the Physiological Properties of the Gonads as Controllers of
Somatic and Psychical Characteristics," I., II., III., and IV., Jour, of Exp. Zool.,
vol. xxviii., 1919, and vol. xxxiii., 1921.

698

THE PHYSIOLOGY OF REPRODUCTION

hermaphrodites, and thus shown that, contrary to Steinach's con-
clusions, the gonads do not necessarily act antagonistically. The
individuals with the grafts, however, possessed the psychical

FIG. 172. — Feminised (originally male) guinea-pig with large
protruding teats and small penis. (From Steinach.)

FIG. 173. — Normal male guinea-pig with rudimentary
teats and large penis. (From Steinach.)

characteristics of the determined or original sex ; thus, while males
with ovarian grafts showed great development of the mammae,
the psychical characters were male. With individuals previously
castrated the grafts produced a reversal of psychical characters.

THE FACTORS WHICH DETERMINE SEX 699

The effects on growth are noteworthy. After early removal of the
gonad the growth curve of the determined male was always higher
than that of the determined female. But the difference was
accentuated by the presence of an ovary, which thus inhibited the
growth.1

Pezard's2 experiments with fowls show that castration and
ovariotomy lead to the development of a neutral type. The removal
of the testis inhibits the growth of the comb and other erectile
structures (wattles and auricular appendages), the capacity to crow
and the combative instincts, but it does not affect the spurs on the
characteristically male plumage. The latter are inhibited in the hen
by the ovarian influence, and as Goodale also has shown, if the
ovaries be removed the spurs grow and a brilliantly developed type
of plumage is produced, such as one ordinarily associates with the
male, but is in reality of a neutral type.

In view of these and other experiments (such as those of Tandler
and Keller on oxen, in which the shape of the head is said to be
similar in male and female " castrates "), Lipschlitz 3 has elaborated
the idea of an indifferent or asexual embryonic form which becomes
male or female according to whether it is acted on by male or female
internal secretions. It will have been seen that whereas in Mammals
the fully developed neutral or indifferent type is in its somatic
characters much nearer to the female, in birds it is closer to the
male. Whether or not this is correlated with the apparent fact
that in Mammals the male is heterozygous as regards sex, while in
birds the female is heterozygous, is an open question.

GENERAL CONCLUSIONS

If it be true that all individuals are potentially bisexual (one of
the two sexes being recessive or latent excepting in hermaphrodites),
and that changed circumstances, leading to a changed metabolism,
may, in exceptional cases, even in adult life, cause the development
of the recessive characteristics (as in the case of the Crustaceans
mentioned above), it would seem extremely probable that the
dominance of one set of sexual characters over the other may be
determined in some cases at an early stage of development in response

1 Cf. Stotsenburg who found with rats that the testis had no effect on the
growth, but that ovariotomy caused an increase of growth by 17-33 per cent.
(Anat. Rec., vol. iii., 1909, vol. vii., 1913, and vol. xii., 1917).

2 Pezard, " Secondary Sexual Characters and Endocrinology," Endocrinology,
vol. iv., 1920. "Modifications Periodiques ou Definitives des Caracteres
Sexuels Secondaires et du Comportment chez les Gallinacees," Annales des Sci.
Nat. (Sees. Sot. et Zool.\ Paris, 1922.

3 Lipschiitz, " L' Action sp6cifique de la Secretion interne des Glandes
Sexuelles, etc.," La Revue Scientifique, Paris, 1921.

700 THE PHYSIOLOGY OF REPRODUCTION

to a stimulus which may be either internal or external. The observa
tions which Riddle, Steinach, and others have made upon animals of
many different kinds point even to the possibility that sex may be
reversed after it has once been established.

It seems certain that sex is not determined by the same factors
in all cases, neither is it determined at the same period of development.
It may well be that some gametes have an initial tendency to give
rise to males and others to give rise to females, and to this extent it
is probably legitimate to speak of male and female ova or male and
female spermatozoa. Moreover, the conclusion is probably correct
that these are developed (at least generally) in simple Mendelian
ratios. But it is also probable that no gamete is either purely male
or purely female, and it is possible that in some the two kinds of
sexual determinants or tendencies are about equally represented.

When once we admit the existence of latent (i.e. recessive) sexual
characters in individuals in which the characters of one sex are
dominant, and that under certain circumstances those of the latent
sex can develop at the expense of the dominant ones, in response to
appropriate physiological stimuli, we are compelled to acknowledge
also that the sex of the future individual is not always predetermined
HI the gametes or even in the fertilised ovum, but may be called into
being at a later stage of life.

Such an admission is of course opposed to some extent to the
modern tendency to believe that sex is fixed irrevocably in the
fertilised ovum or in the gametes before fertilisation. But while there
is evidence amounting to proof that this is the case in some forms of
life, it does not necessarily follow that it is true of all Metazoon
animals, or even that it is uniformly so of the particular species
which have been investigated. On the other hand, many of the facts
enumerated above point to the conclusion that the sex of the future
organism is determined in different cases by different factors and at
different stages of development — either in the unfertilised gamete, or
at the moment of fertilisation, or in the early embryo.

Finally, there is evidence that a change in the metabolism, even
in comparatively late life, whether induced by castration or the
introduction of another gonad or arising primarily from a different
cause, may initiate changes in the direction of the opposite sex, or
even bring about a complete sex- reversal.1

1 For a complete review of Champy's work on Triton, see Champy, " Etude
experimentale sur les Differences sexuelles chez les Tritons," Arch. d. Morph.
Exper. (Fasc vii.), 1922. See also Swingle, " Is there Transformation of Sex
in Frogs?" Amer. Jfat., vol. Ivi., 1922. The latter author throws doubt on
Witschi's conclusions.

CHAPTER XVI

PHASES IN THE LIFE OF THE INDIVIDUAL— THE
DURATION OF LIFE AND THE CAUSE OF
DEATH.

" Tavrbv yap r}/2aW avSpa Kal Trpe(r/3vv daveiv • " — EURIPIDES, Ahestis.

THE physiological life of the metazoon individual begins with the
union of sperm and ovum, and the organism thus formed thenceforth
proceeds to grow. As has been said by Yerworn,1 there is an essential
similarity between reproduction and growth, both processes consisting
of an increase of living substance. " The difference between that
which is usually termed growth in the narrow sense and the
phenomenon of reproduction consists only in the fact that in the
former case the newly-formed living substance remains in constant
connection with the original organism and helps to increase its
volume ; while in the latter case a part of the substance separates
itself from the original organism, either, as in most cases, being set
entirely free, or, as in the increase of tissue-cells, being separated
merely by a partition wall and remaining in place." Among the
more highly organised Protozoa there are various transitional stages
between these two conditions.

Growth, like reproduction, involves cell division. As the mass of
living substance increases, the cells must multiply, for every cell has
assigned to it a limit in size beyond which it cannot pass. Cell
division goes on, though with gradually decreasing frequency,
throughout practically the whole of life ; tissue formation continues,
but from an early period of development onwards there is a progressive
diminution in the power of growth.' Increase in the number of cells
is, however, specially characteristic of the embryonic period. In the
later stages of development growth occurs in great measure through
cell enlargement and the deposition of intercellular substance.

Minot has compared the growth of the body to a man building
a wall.2 " He begins at first with great energy, full of vigour ; the
wall goes up rapidly ; and as the labour continues, fatigue comes into

1 Verworn, General Physiology, Lee's Translation, London, 1899.

2 Minot, " The Problem of Age, Growth, and Death," Popular 8ci«n<*e Monthly,
vol. Ixxi., 1907 ; reprinted London, 1908.

702 THE PHYSIOLOGY OF REPRODUCTION

play. Moreover, the wall grows higher, and it takes more effort and
time to carry the material up to the top of the wall, and to continue
to raise its height, and so, as the wall grows higher and higher, it
grows more slowly and ever more slowly, because the obstacles to be
overcome have increased with the very height of the wall itself. So
it seems with the increase of the organism, and with the increase of
our development, the obstacles to our growth increase." According
to Minot, the explanation of this phenomenon must be sought in the
differentiation of the protoplasm, which goes on growing with an
ever-increasing complexity as the cells of the body multiply.

It has just been mentioned that every cell has assigned to it
a definite limit in size beyond which it cannot go. Boveri1 has
enunciated the general law that the process of cell division is
regulated by the proportion of chromatin material to cytoplasm,
and that it comes to a standstill when the ratio of the mass of
chromosomes to that of the cells in any given tissue or organ reaches
a certain definite point. Furthermore, it is stated that the size of
the cells in any given tissue after active cell multiplication has
ceased, bears a definite relation to the original mass of chromatin
contained in the fertilised egg.2 Thus it is pointed out that the
mesenchyme cells of the embryo developed from the artificially
fertilised sea-urchin's egg are only half the size of those of the
embryo which has been produced by normal fertilisation, for although
the parthenogenetic and normally fertilised eggs are equal in size at
the commencement of segmentation, the latter possess initially twice
as much nuclear substance as the former.3

The fact that cell division ceases when the ratio of the mass of
chromosomes in the nuclei of an egg (or of a tissue or organ) to that
of the surrounding protoplasm reaches a certain definite limit, is
regarded by Loeb 4 as evidence that this ratio is determined by the
laws of mass action and chemical equilibrium. He says further
that if this conclusion is correct the synthesis of nuclein com-
pounds, from their protoplasmic constituents, must be a reversible
process.

The fertilisation of an ovum is immediately succeeded by an
enormous synthesis of nuclear material. In the cellular division
which follows, each new nucleus is of the same size as the parent

1 Boveri, Zellen-Studien, Part V., Jena, 1905.

2 Robertson, " On the Normal Eate of Growth of an Individual and its Bio-
chemical Significance," Arch. f. Entwick.-Mech., vols. xxv. and xxvi., 1908.
" Studies in the Growth of Man," Amer. Jour, of Phm., vol. xxxvii., 1913.
See also Feldman, Principles of Ante- Natal and Post-Natal Child Physiology,
London, 1920.

3 Driesch, " ITber das Mesenchym von unharmonisch zusammengesetzten
Keimen der Echiniden," Arch. f. Entwick.-Mech., vol. xix., 1905.

4 Loeb, The Dynamics of Living Matter, New York, 1906.

PHASES IN THE LIFE OF THE INDIVIDUAL 703

nucleus. From this fact Loeb x concludes that the nucleus itself, or
one of its constituents, acts as a catalyser in the synthesis of nuclein
in the fertilised ovum. Robertson,2 quoting partly from Loeb, writes
as follows : " If the mass of the original fertilisation nucleus be m,
the mass of nuclear material increases during the first segmentation
period to 2m, during the next to 4wt-, and so on in geometrical
progression. The duration of the various periods of segmentation,
however, matters very little. Hence in the first unit of time after
the beginning of cell division, a mass m of nuclear material is
formed, in the second a mass 2m, in the third a mass 4w, and so on ;
thus the velocity of the synthesis increases with lapse of time and
with the mass of nuclear material already formed. This is a
characteristic of that class of reactions known as autocatalytic, in
which one of the products of the reaction, or, in this case, one of the
constituents of ~ the nucleus, accelerates the reaction. During the
process outlined above, an emphatic disproportion between nuclear
and protoplasmic material has been established. As the nuclear
synthesis becomes slower, however, the disproportion tends to adjust
itself until, finally, the growth of the organism consists almost
entirely of the growth of protoplasmic material, and in the final
re-establishment of the equilibrium between cytoplasm and nuclear
material."

Robertson has investigated mathematically the quantitative
relations which exist between the amount of growth and the time
of growth. He concludes that there are two or more growth cycles
representing autocatalytic processes which make up the total growth
of an individual. In man there are three maxima of rate of growth,
representing three phases or growth cycles. One of these is intra-
uterine, but it is probable that this is not quite complete at birth.
The second growth cycle seems to attain its maximum annual
increment at about the fifth year, since the increment in weight
at that age, as deduced from an investigation on growth in English
boys, considerably exceeds the annual increments for the years
immediately following. A third maximum in yearly increments
occurs in males at about the sixteenth year, that is, at about the time
of puberty. In the rat, according to Donaldson,3 there are two
intra-uterine growth cycles, while there is only a single well-defined
extra-uterine cycle. Robertson suggests that the first growth cycle

1 Loeb, " Weitere Beobachtungen iiber den Einfluss der Befruchtuiig, etc.,"
Bio. Chem. Zeitsch., vol. ii., 1906. "The Chemical Character of the Process of
Fertilisation and its Bearing on the Theory of Life Phenomena," Seventh
Internat. Congress, Boston, University of California Publications, vol. iii., 1907.

2 Robertson, loc. cit.

3 Donaldson, " A Comparison of the White Rat with Man in respect to the
Growth of the Entire Body," Boas Anniversary Volume, Anthropological Papers,
New York, 1906.

704

THE PHYSIOLOGY OF REPRODUCTION

in Mammals represents the course of the autocatalytic synthesis of
the nuclear substance, that the third cycle represents the period
during which cytoplasmic material is built up, while the second
growth cycle is intermediate, representing a time when both

synthetic processes go on con-
temporaneously.

600%

500%,

400%

300%

200%

100%

GROWTH OF THE BODY BEFORE
BIRTH

Minot1 has recorded the
results of weighing embryo
rabbits at different stages of
development with a view to
determining their rate of growth.
The results showed that in the
period from the ninth to the
fifteenth day the young rabbit
adds on an average 704 per
cent, to its weight daily, and
that in the period from the
fifteenth to the twentieth day,
the average daily addition is
only 212 per cent. It may be
assumed, therefore, that in
younger embryos (before the
ninth day) there is an increase
of over a thousand per day.
Minot estimates that over
ninety-eight per cent, of the
original power of growth of the
rabbit or the chick has been lost
at the time of birth or hatching,
and that a similar fact is equally
true of man. " We start out at
birth certainly with less than
two per cent, of the original
growth power with which we
were endowed. Over ninety-
eight per cent, of the loss is accomplished before birth — less than
two per cent, after birth." The accompanying diagram represents
reughly the rate of growth in man before birth. The time intervals
correspond to the ten lunar months of gestation. The rate of
increase in the first three months is not indicated, since there are

1 Minot, loc. cit.

\

FIG. 174.— (Prom C. S. Minot's Problem
of Age, Growth, and Death, G. S. Put-
nam & Sons, and John Murray.)

PHASES IN THE LIFE OF THE INDIVIDUAL 705

no statistical data on which to found any knowledge, but from the
third month onwards there are a few records available. The
diagram shows that from the third to the fourth month the increase
in growth is 600 per cent., after which it quickly drops until, during
the last month of pregnancy, it is barely twenty per cent.

GKOWTH OF THE BODY AFTER BIRTH

The rate of growth from birth to maturity has been investigated
most fully by Minot1 in the case of the guinea-pig. When this
animal is born it is far advanced in development, the period ol
gestation being unusually long. Immediately after birth there is a
lessening in the power of growth, a fact which Minot ascribes to the

\

Z 5811 n 23 29 J535 45

75 90 105 120 135 ISO 165 ISO 195 2IOiiajfc> 2*1

FIG. 175. — (From Minot's Problem of Age, Growth, awl Death,
G. S. Putnam & Sons, and John Murray.)

physiological shock from which the organism suffers as a consequence
of being born. After two or three days, however, the young are
fully recovered, and are capable of adding over five per cent, to their
weight in a single day. By the time they are seventeen days old
they are only able to add four per cent, to their weight, and by the
time they are twenty-four days old, less than three per cent. When
they have been born forty-five days, they can add only a little over
one per cent, to their weight ; when ninety days old, less than one
per cent., and 'still less as they grow older, until when about a year
old they attain their full size. The curves in the accompanying
diagrams show the daily percentage increments in weight in male
and female guinea-pigs respectively, as ascertained by Minot. It is
seen that the curve for the females is very similar to that for the

1 Minot, "Growth and Senescence," Jour, of Physiol, vol. xii., 1891. "Age,
Growth, and Death," Popular Science Monthly, vol. Ixxi., 1907.

23

706

THE PHYSIOLOGY OF REPRODUCTION

males. Both show an early period of rapid decline in which the rate
of growth is quickly diminishing, followed by a period of slight
decline in which the curve is still falling, but very much more
gradually (Figs. 175 and 176).

Minot has also investigated the rate of growth in the rabbit and
in the chicken.' The young rabbit, as is well known, is born in a
very immature state of development after a relatively short gestation
period. Correlated with this fact, it was found that the male rabbit
four days after birth is capable of adding over seventeen per cent, to
its weight in a single day. From that time the percentage increment
drops very rapidly, so that at an age of twenty-three days the rabbit
can only add a little over six per cent. After about the fifty-fifth
day the decline in the growth rate, which has hitherto been rapid,

2 sen " a a xx

FIG. 176. — (From Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray. )

becomes more gradual. In the case of the chicken, Minot's results
were in a general way similar, but the rate of growth on the first
day it could be measured was a nine per cent, addition to the weight,
while the change from the initial rapid decline to the subsequent
slow decline was more gradual than in the other two animals.1

The mean weight of the foal at birth is said to be 112 Ibs.
During the first three months the average daily increase is 2'2 Ibs. ;
from three up to six months it is 1*3 Ibs. ; and from six months
up to three years 0'7 lb. It is said that probably many horses
continue to grow until they are six years old.2

The calf at birth weighs about 77 Ibs., and the average daily

1 For an exhaustive account of the growth phenomena in the rat, in which
the growth curve is in a general way similar to that of the rabbit, see Donaldson,
The Rat (Wister Institute Memoirs, No. 6), Philadelphia, 1915.

2 Smith (F.), Veterinary Physiology, 3rd Edition, London, 1907.

PHASES IN THE LIFE OF THE INDIVIDUAL 707

increase during the first two years is 1/5 Ibs. With the sheep
the increase is greater, for a young lamb in ten days can add fifty
per cent, to its original weight, and can double it at the end of the

038131833283338 55

I06t

180

FIG. 177. — (From Minot's Problem of Age, Growth, and Death,
» G. S. Putnam & Sons, and John Murray.)

first month, and treble it at the end of the second. In pigs,
however, the increase is even more rapid, for a young pig can add
twenty per cent, to its original weight by the end of the first week,
and up to the end of the first year can add an average daily increase
of 0-44 Ib.

;o8

THE PHYSIOLOGY OF REPRODUCTION

Murray,1 who has investigated the laws of growth in various
animals, tinds that whereas the growth of sheep, rabbits, and chickens
appears to conform to a general principle which may be expressed as
a simple formula, and represented in a simple curve, with cattle

038I3I8?3?833
38

FIG. 178. — (From Minot's Problem of Age, (Irowth, and Death,
G. S. Putnam & Sons, and John Murray.)

there is evidence of an acceleration in the rate of growth between
the first and second year, similar to the prepubertal acceleration in
man described below and shown in the diagram (Fig. 182). Murray

1 Murray, " Normal Growth in Animals," Jour, of Agric. Science, vol. xi.,
1921.

PHASES IN THE LIFE OF THE INDIVIDUAL 709

points out that if there is a second period of acceleration in cattle at
about the age of sixteen or seventeen months, of which evidence is
adduced, this period would be the most economic one for slaughtering
for beef, especially if the animals can be brought to the desired
condition of fatness at the same time.

Mackenzie and the present writer1 have shown that the most
economic state of fatness in which to slaughter cattle is that
represented by an average carcass-to-liveweight percentage of
about fifty-six — and that this condition can be well attained at the
age in question. Very fat beasts are produced at a cost of
much waste, and owing to the excess of "offal" or internal fat
removed with the alimentary canal and other parts, their carcass
percentage is apt to be lower than with beasts whose condition is

03$ 8 13 IB& 283338 4« 56 66 '7 90

FIG. 179. — (From Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)

poorer. Hammond,2 who has made a close study of the biometry of
growth in various breeds of domestic animals, makes a similar
statement for sheep.

In man growth is most rapid during the first year of life; when a
child is able to increase its weight by 200 per cent. For the second
year this percentage drops to twenty, and for subsequent years up
to about the age of thirteen, it fluctuates around ten, showing a
gradual tendency to decrease (but cf. Robertson, quoted on p. 703).
After this there is a distinct increase in the percentage increment

1 Mackenzie and Marshall, " Beef Production " (Abstract), Jour. Board of
Agric. and Fisheries, vol. xxv., 1918. See also chapter on Physiology in
Mackenzie's Cattle, Cambridge, 1919.

2 Hammond, " On the Relative Growth and Development of Various Breeds
and Crosses of Cattle," Jour, of Agric. Science, vol. x., 1920 ; and " On the Relative
Growth and Development of Various Breeds and Crosses of Sheep," Jour, of
Agric. Science, vol. xi., 1921. These papers contain a full account of the literature.

;io THE PHYSIOLOGY OF REPRODUCTION

representing the prepubertal and pubertal growth. Then there is a
further decline in the power of growth, which gradually diminishes.
The prepubertal growth of girls usually precedes that of boys, so
that between the ages of twelve and fifteen girls are often heavier
and taller than boys. Boys grow most rapidly at sixteen, girls at
thirteen or fourteen. Boys attain their full height at from twenty-
three to twenty-five years of age; girls at twenty or twenty-one.
In both sexes the weight of the body tends to increase until about
the fiftieth year or somewhat later, owing to an accumulation of fat,
but there are of course very many exceptions.1

That good nourishment and a healthy environment favour growth
is a fact recognised by all. So also systematic exercise has been

56 66 7) 90 - K>6

FIG. 180. — (From Minot's Problem of Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)

found to increase both the weight and the height,2 and it has been
shown further that well-developed children are more efficient
mentally and take better places at school than ill-developed and
badly-nourished ones.3

In horses and other domestic animals the effects of feeding on
growth and general development are remarkable. Thus it is said
that a highly-fed thoroughbred at two years old is " furnished " and
looks as old as an ordinary horse at four years old.4

1 See Minot, Popular Science Monthly, vol. Ixxi., 1907. Minot states that his
calculations are based on data supplied by Professor Donaldson. See also Lee,
Article "Reproduction," in Howell's American Text-book of Physiology, 2nd
Edition, London, 1900.

2 Beyer, " The Influence of Exercise upon Growth," Jour, of Exp. Mad.,
vol. i., 1896.

3 Porter, " The Physical Basis of Precocity and Dulness," Trans. A cad. of
Science, St. Louis, vol. vi., 1893.

4 Smith, loc. cit. For growth in pigs, see Hammond, Jour, of Agric. Sci., 1922.

PHASES IN THE LIFE OF THE INDIVIDUAL 711

Live
Weight
(Ib.)
175

150
125
100
75
60
25

30 35

J [_

40 45
I I

50 55 weeks
I I

FIG. 181. — Growth of sheep. (From Alan Murray, Jour, of Agric. Science.)

Curve 1, Suffolk sheep (males, single).
„ 2, „ „ (females, single).

„ 3, Shropshire + Merino sheep (males, single).
„ 4, „ „ „ (females, single).

„ 5, „ „ „ ( „ twins).

The weights actually observed are indicated by ® for the Suffolk, and
for the Shrop.-Merino sheep.

Increase
(kg)

FIG. 182. — C4rowth of girls (A) and boys (B) ; increase kg. per annum. Prior to
the tenth year the rate of growth of the two sexes is represented by the
same line. (From Alan Murray, Jour, of Agric. Science.)

712 THE PHYSIOLOGY OF REPRODUCTION

The various other external factors that influence growth in
animals of different kinds are discussed by Morgan in his work on
" Experimental Zoology," l to which the reader is referred for an
account of the literature of the subject.

The internal factors or conditions which control growth have
been recently investigated by Eobertson and Ray,2 who show that
early growth in mice is due to over-increase of the cellular elements
or parenchymatous tissue, as distinguished from the sclerous or
connective tissues. They state that early overgrowth is correlated
with longer life, the individuals displaying it being highly resistant
to external disturbing factors and tending towards a relative paucity
of tissue accretion late in life. Short-lived individuals, on the
contrary, are relatively unstable and sensitive to external influences,
and tend to display a relatively deficient early growth but rapid and
unstable accretions of connective tissue elements in late life. Such
accumulations are notoriously characteristic of old age, and their
presence throws a strain on the metabolism of the cellular elements
which support these accretions, and consequently tend to shorten
life. The administration of tethelin or cholesterol, which was found
to prolong life, led to an increased anabolism of the distinctively
cellular elements to the disadvantage, in the competition for
nutriment, of the connective tissue. If tethelin was given to mice
only so long as they were immature, the cessation of this stimulus was
followed by a great increase in size. Such increase was due to the
growth of the sclerous tissue, and added to the already highly
developed cellular tissue (hitherto not noticeable) resulted in
gigantic individuals. It was shown also that brain tissue from
which the cholesterol had been extracted was without effect upon
growth, whereas nervous tissues not so treated stimulated anabolism.

PUBERTY

Puberty, or the period at which the organism becomes sexually
mature, is marked by the occurrence of those constitutional changes
whereby the two sexes become fully differentiated. It is at this
period that the secondary sexual characters first become conspicuous,
and the essential organs of reproduction undergo a great increase in
size,3 while in those animals in which during immaturity the testicles

1 Morgan, Experimental Zoology, New York, 1907. See also Robertson and
Ray, " Experimental Studies on Growth," Jour, of Biol. Chem., vol. ^xxiv., vol.
xxv., 1916, and vol. xxxvii., 1919.

2 Robertson and Ray, " Experimental Studies of Growth," XV. and XVI.,
Jour, of Biol. Chem , vols. xlii. and xliv., 1920. For Child's views on growth,
see above, p. 225.

3 Disselhorst, "Gewichts und Volumszunahme der mannlichen Keimdriisen,
etc.," Anat. Anz., vol. xxxii., 1908.

PHASES IN THE LIFE OF THE INDIVIDUAL 713

remain within the body cavity, it is at puberty that these organs first
descend into the scrotal sacs. The puberty acceleration in growth
which takes place in man has been already referred to. This change
is accompanied, as is well known, by alterations in the general
proportions, associated with an increase of strength, a deepening of'
the voice, and a growth of hair on the face and other parts of the
body, processes which are not completed until about the twenty-fifth
year.1 In temperate climates puberty begins in boys at about the
fourteenth or fifteenth year ; in tropical countries it is usually a few
years earlier.2 It is at this period that ripe spermatozoa first make
their appearance in the seminal fluid, which is henceforward secreted
in considerable quantity.

In women puberty occurs at a slightly earlier age than in the
male sex. The constitutional changes characterising this period take
place more suddenly in the female, the girl almost at once becoming
a woman, whereas the boy is several years before he develops into a
man, complete maturity not being reached until the twenty-fifth year.
Moreover, the onset of puberty in the girl is marked more precisely by
the coming of menstruation, which may make its appearance in temper-
ate climates in the thirteenth year. At about the same time the pelvis
widens, and the other characteristic anatomical changes take place ;
the subcutaneous layer of fat, the development of which assists so
largely in giving the body its graceful contour, is deposited ; while
the internal generative organs enlarge and ripe ova are produced by
the ovary.3

1 The breaking of the voice occurs to a certain extent also in girls but less
sudden. Appended is Earth's table of the length of the vocal cords at different
ages (as quoted from Feldman, Ante-natal and Post-natal Child Physiology,
London, 1920).

Age in years -

0

2

6

10

14

20

30

Males, mm. -

6

8

10

13

13

24

30

Females, mm.

6

8

10

12

12

16

20

It is thus seen that the lengthening of the cords even in boys is not
absolutely sudden but extends over years.

2 Havelock Ellis, Man and Woman, 5th Edition, London, 1914. This book
contains a wealth of information concerning growth, etc., and many other
matters. Steinach and Kammerer, "Klimak und Mannbarkeit," Arch. f.
Entwick.-Mech., vol. xlvii., 1921.

3 Runge (E.), however (" Beitrag zur Anatomic der Ovarien Neugeborener
und Kinder von der Pubertatzeit," Arch. f. Gynak., vol. Ixxx., 1906), states
that growing follicles are by no means uncommon in ovaries of young children.
In the first year of life he found follicles of considerable size, and in the second
year still larger ones, some having a diameter of 135 /*. In the third year
degenerate follicles were also found. During this and the following years there
was a progressive increase in the size of certain of the follicles until the ovaries
became scarcely distinguishable from those of adults excepting for their smaller

23 A

THE PHYSIOLOGY OF REPRODUCTION

In both sexes the purely physical changes of puberty are
accompanied by psychical ones which are no less pronounced. Both
kinds of change are dependent largely, if not entirely, upon the
functional development of the generative glands.1

In animals the general nature of the change which sets in at
puberty is similar to that occurring in the human species, and the
secondary sexual characters often appear for the first time at this
phase of life. Excepting in the case of the domestic animals, little is
definitely known concerning the respective ages at which the different
species become mature. Most fillies come in use within two years,
and all by the time they are three. Cows may come on heat when
a year old, but it is best to postpone service until three months later.
A good deal depends on nutrition, but even starved and backward
cows will receive the bull when fifteen months old. Sows will receive
the boar when six months old, and sometimes two months earlier.
Sheep will breed at the age of six months (that is to say, lambs
born in the spring will breed in the following autumn), but the practice
is to be deprecated in the interests both of the ewes themselves and
of their lambs. Dogs will breed when about ten months old or even
earlier (sometimes seven), but the larger kinds do not breed so soon.
Cats are similar. Rodents may breed when still younger, but whether
they do so or not depends upon the season of the year and other
conditions of environment and nutrition. The white mouse is stated
to breed when six weeks old,2 the white rat at about two months,3 and
the domesticated rabbit at about five months.

It should be remembered that in animals as in man complete
sexuality is not acquired all at once in either sex. Thus, in actual
practice, ram lambs are not allowed to serve more than 20 or 25
ewes in a season, as against 40 or 50 which older rams may serve.
Similarly with stallions, a yearling may serve 15 mares in a season,
a two-year old 60, while an adult may serve 80 to 120' mares.

THE MENOPAUSE

In the male sex (as already mentioned) there is no definite age
at which the reproductive functions cease. In the female, on the

size. Runge states further that in one instance he found a corpus luteum in
an ovary of a recently born child, but this must be regarded as very exceptional.
As a result of his observations, Runge concludes that follicular maturation sets
in during infancy and not at puberty. Ovaries of human embryos showed
growing follicles only in very rare instances.

1 For further extensive information see Stanley Hall, Adolescence, New
York, 1904.

2 Kirkham, " The Life of the White Mouse," Proc. Soc. Exp. Biol. and Med.,
vol. xvii., 1920.

3 Donaldson, foe. cit. Evans and Bishop state that the first cestrus occurs
between the thirty-seventh and fifty-fifth day ("On the Relations between
Fertility and Nutrition," Jour, of Metabolic Research, vol. i., 1922).

PHASES IN THE LIFE OF THE INDIVIDUAL 715

other hand, the close of the reproductive period is far more definite,
and it is this change in the human female which constitutes the
menopause or climacteric. The essential phenomenon of, the meno-
pause, therefore, is the permanent arrest of all the functions
connected with reproduction.1 It is the inversion of the develop-
mental process of puberty, and marks the termination of active
sexual life. In temperate climates it almost always takes place
between the ages of forty and fifty, and most usually at about the
age of forty-five.2 In warm countries it has a tendency to be earlier,
and in colder ones later. It is usually earlier among the labouring
classes, and also in women in whom puberty was early. The actual
duration of the period when menopause symptoms occur varies from
about three to five years.

The symptoms of the menopause may be referred to two stages —
(1) a stage of menstrual irregularity, and (2) a post-cessation stage,
during which various systemic disturbances are wont to occur.
During the latter period especially the organic functions are
irregular. Palpitation, dyspepsia, sweating, and vasomotor changes
are not infrequent, and neurasthenic phenomena, hysteria, and other
psychic disturbances sometimes occur, accompanied by neuralgia,
rheumatism, and various disorders. Mental instability at the
"change of life" is not uncommon. It is well known that the
menopause is followed by profound psychological changes which
vary in different individuals. The changes which take place in
the lower Mammals have not been studied, but they can hardly be
so great as those which occur in women.

The anatomical and physiological basis of the menopause is, as
already indicated, the atrophy of the reproductive organs. The
following are the changes which take place in women : —

(1) Senile changes in the ovary : (a) Atrophy, induration, and
shrinkage to the size of the rudimentary ovary ; (b) disappearance
of Graafian follicles and cessation of ovarian functions.

(2) Senile changes in the Fallopian tubes : (a) Shortening and
narrowing, often accompanied by obliteration of the lumen; (b)
destruction of the epithelial cells.

(3) Senile changes in the uterus : (a) Atrophy of the entire organ,
which may be reduced to a hard, wedge-shaped body, one-quarter
the size of the functional organ ; (b) in many cases closure of the
internal os, or of the external os, or complete obliteration of the
canal ; (c) consequent secretions producing pyometra or hydrometra,

1 Cases are on record, however, of women conceiving some years after
the apparent menopause.

2 For further details see Kelly, Medical Gynecology, London, 1908 ; and
Luciani, Human Physiology, English Edition, vol. v., London, 1921.

;i6 THE PHYSIOLOGY OF REPRODUCTION

due to the locking up of the secretions ; (d) in some cases the
disappearance of the vaginal portion, making the upper part of the
vagina continuous with the uterine canal; (e) degeneration of the
muscular and glandular elements ; and (/) cessation of menstruation.
(4) Senile changes in the vagina : (a) Shortening, narrowing, and
loss of elasticity ; (b) loss of pavement epithelium, and substitution
of a hard surface containing cicatricial tissue ; and (c) contraction of
the entrance to the vagina.

FIG. 183. — Section through ovary of woman of fifty-six, showing degeneration
of follicles and sclerosis of connective tissues. (From Sellheim.)

(5) Senile changes in the vulva : (a) Great contraction and loss
of elasticity; (b) destruction of glands and follicles ; and (c) cutaneous
surface becoming dry and scaly.

(6) Senile changes in the mammary glands : (a) Loss of glandular
elements and cessation of function ; and (b) shrinkage due to atrophic
loss, which, however, is sometimes compensated for by a deposition
of fat.1

1 Dudley, The Principles and Practice of Gynaecology, 4th Edition, London,
1905. For a further account of the atrophic changes in the uterus and other
generative organs, see Sellheim.

PHASES IN THE LIFE OF THE INDIVIDUAL 717

Other changes, depending probably on the degeneration of the
ovaries, are the assumption of certain of the secondary male
characters. These are apparently more marked in some animals
than they are in the human species, and have already been men-
tioned in dealing with the internal ovarian secretions (p. 340).

The ages at which domestic animals cease to breed have been
only imperfectly determined since they generally die before reaching
their climacteric. Mares have been known to produce young beyond
thirty years,1 sheep up to twenty, and cats to fourteen, but they may

FIG. 184. — Section through uterine mucous membrane of woman of
sixty. (From Sellheim.) gl, Glands.

cease somewhat earlier and yet maintain a healthy existence for a
few years.2 Kirkham3 says the white mouse stops reproducing at
eighteen to twenty-two months after having twelve to sixteen litters.
The menopause in the white rat occurs at the age of fifteen to
eighteen months.4

1 Wood (W. A.) found that out of 1216 thoroughbred mares recorded in
the earlier volumes of the General Stud-book, one bred at 33, two at 30, four
at 29, seven at 28, and seventeen at 27. He draws the conclusion that in actual
practice the mare generally continues to breed as long as she lives (" Note on
the Breeding Age of Thoroughbred Mares," Vet. Jour., December 1921).

2 Fleming, Veterinary Obstetrics, 3rd Edition, by Craig, London, 1912.

3 Kirkham, loc. cit.

4 Donaldson, loc. cit.

;i8 THE PHYSIOLOGY OF REPRODUCTION

SENESCENCE

As age advances, in addition to the menopause changes which
relate more especially to the cessation of the female generative
functions, atrophic changes of one sort or another take place in both
sexes throughout practically the entire system. The internal spongy
structure of the bones is dissolved away, so that they are left with
only a hard external shell and consequently become brittle. The
teeth decay and drop out. The muscles shrink in volume, the actual
fibres of which they are composed becoming smaller in size and fewer
in number. The arterial walls lose their elasticity and undergo
sclerosis, a characteristic which is so constant that it has given rise
to the well-known dictum that "a man is as old as his arteries."
The tendons and ligaments also become calcified, and there is a

FIG. 185. — Section through vaginal mucous membrane of woman of
sixty-one. (From Sellheim.)

consequent shrinkage of stature. The size of the liver and other
viscera undergoes diminution, but the kidney and heart retain their
size ; in fact the heart is usually slightly enlarged in old age, but this
apparent hypertrophy is not associated with an accession of power
but with an increased feebleness, and the pulse, in order to
compensate for the weakness of the enlarged heart, beats more
quickly, the normal rate of seventy-two beats per minute rising to
seventy-nine or eighty. The rate of respiration also rises slightly,
and the vital capacity of the lungs diminishes. Moreover, the
amount of carbon dioxide and urine which are excreted becomes less.
The pigment in the hair undergoes absorption, the hair turning grey
or white. The adipose tissue beneath the skin disappears, especially
in advanced old age, but fatty degeneration of muscle or glandular
tissue is not infrequent. In the male sex the prostate gland under-
goes atrophy, or in some cases a pathological hypertrophy, which is
said to be the cause of frequent penile erections.

PHASES IN THE LIFE OF THE INDIVIDUAL 719

It has been shown also that the brain decreases in size in old age.
The shrinkage begins soon after maturity, and then continues almost
steadily to the very end of life.1 Handmann2 has published the
following statistical results, which are based on measurements
carried out at the Pathological Institute at Leipzig : —

Weight of Brain.

Age.

4-6 -
7-14
15-49
50-84

Male.

1215 grams.
1376 „
1372 „
1332

Female.

1194 grams.
1229 „
1249 „
1196

The decrease in brain weight is accompanied by a diminution in
the thickness of the cortex and in the number of tangential fibres
present in it. These changes are
associated on the psychical side
with a gradual mental failure —
loss of memory, decrease in the
power of original thought and in
the assimilation of new ideas, and
general decline of mental activity.
Moreover, the reaction time is
lengthened, the sense organs lose
their delicacy, and in the eye
the power of accommodation is
largely lost.

The minute cellular changes
in the tissues are no less pro-
nounced. These also are in the
direction of atrophy. There is a

general shrinkage in the proto-
plasm of the cells, but especially
in the nuclei, so that the relative
amount of cytoplasmic to nuclear
substance becomes increased in
old age. The nucleoli also tend to

disappear. Hodge3 has made a comparison of the changes in the
cells of the first cervical ganglion with the following result : —

FIG. 186. — Group of nerve-cells from
the first cervical ganglion of a
child at birth. (After Hodge,
from Minot's Age, Growth, and
Death, G. S. Putnam & Sons, and
John Murray.)

At birth
At 92 years

Volume of Nucleus.

100 per cent.

- 64-2 ,

Nucleoli observable
in Nitcleus.

In 53 per cent.

n 5 »i

1 Minot, loc. cit.

2 Handmann, " Uber das Hirngewicht des Menschen," Arch. f. Anat. u. Phys.,
Anat. Abth., 1906.

3 Hodge, "Die Nervenzelle bei der Geburt und beim Tode an Alterschwache,"
Anat. Anz., vol. ix., 1894.

720 THE PHYSIOLOGY OF REPRODUCTION

Thus the nucleoli are often apparently quite absent in extreme old
age. The nuclei, besides becoming smaller, grow irregular in shape,
and in the cytoplasm there is a deposition of pigment granules.

Senescence in men is said to commence at about the age of fifty,1
but it is obvious that no definite limit can be assigned to the period,
since in some of the organs changes which are in their nature
degenerative begin quite early in life.

Spermatozoa continue to be produced even in quite advanced old
age, and instances have been recorded of men of 94, 96, and even 103 in

c^^^^K^^f' ' '• Iff/
•«/IlK :$Mdm. ^n^

FIG. 187. — Group of nerve-cells from the first cervical ganglion of a man of
ninety-two. (After Hodge, from Minot's Age, Growth, and Death,
G. S. Putnam & Sons, and John Murray.)

C, C, Cells still intact, but shrunken and loaded with pigment ;
c, c, cells which have disintegrated.

whose semen active sperms were found.2 There can be no doubt,
however, that the spermatozoa are produced in far less abundance in
old age.

In women the period of senescence is usually reckoned from the
menopause.3

It is difficult to form any accurate comparison between the
phases of life of men and those of animals, partly because so little is
known regarding the conditions of natural senescence and death in

1 Lee, loc. cit.

2 Cooper, The Sexual Disabilities of Man, etc., London, 1908.

3 For further information bearing on the subject see Stanley Hall, Senescence,
New York, 1922.

PHASES IN THE LIFE OF THE INDIVIDUAL 721

animals. Smith 1 remarks that few horses live long enough to show
much sign of arterial degeneration. The work they perform is the
chief cause of their rapid decay, for their legs wear out before their
bodies. But, apart from this, degenerative changes in the teeth, and
more particularly the wearing away of the molars, prevent many
horses from reaching a real old age. Elaine2 has drawn the
following comparison between the age of a horse and that of a
man : " The first five years of a horse may be considered as
equivalent to the first twenty years of a man ; thus, a horse of five
years may be comparatively considered as old as a man of twenty ; a
horse of ten years as a man of forty ; a horse of fifteen as a man of
fifty ; a horse of twenty as a man of sixty ; of twenty-five as a man
of seventy ; of thirty as a man of eighty ; and of thirty-five as a
man of ninety."

THE DURATION OF LIFE AND THE CAUSE OF DEATH

Weismann, in a famous essay on the duration of life,3 and
Metchnikoff in his book of optimistic studies,4 have dealt at some
length, but from different standpoints, with the factors which
determine longevity in the animal kingdom. That the duration of
life in the various races of animals is very variable, and that, whereas
some species are remarkably long-lived, others die after a relatively
brief existence, are facts that are known to all. Both Weismann and
Metchnikoff cite numerous instances of longevity among animals,
some of the more extreme of which may be mentioned here.

A sea-anemone belonging to the species Actinia mesenibryan-
themum is known to have lived for sixty-six years, and to have
produced young, though in smaller numbers than formerly, at the age
of fifty-eight. Another sea- anemone of the species Sagartia
troglodytes lived to be fifty years old.5 Certain marine Mollusca are
said to live for as many as a hundred years. Among insects there is
an extraordinary variability in the duration of life, some living in a
condition of maturity for only a few days or even hours, while others
(certain Hemiptera) are believed to survive for as many as seventeen
years. Moreover, the duration of life is sometimes very different in
the two sexes, the queen ant being known to live for several years (in
one case for fifteen years), whereas the male ant survives for only a
few weeks.

1 Smith, loc. cit.

2 Blaine, Encyclopaedia of Rural Sports, London, 1858.

3 Weismann, "The Duration of Life," English Translation, in Essays upon
Heredity, etc., 2nd Edition, Oxford, 1891.

4 Metchnikoff, The Prolongation of Life, English Translation, London, 1907.

5 Ashworth and Annandale, "On Some Aged Specimens of Sagartia," Proc.
Roy. Soc. Edin., vol. xxv., 1904.

722 THE PHYSIOLOGY OF REPRODUCTION

Among fish, pike and carp are usually said to attain to great ages
and even to live for centuries, but there are few accurate data.

Among reptiles, crocodiles and tortoises are known to have long
lives, a tortoise from the Galapagos Islands being stated to have lived
for 175 years.

The length of life in birds has been discussed by Gurney,1 who
cites several examples of great longevity, but the more usual duration
of life is from fifteen to twenty years. Canaries are stated to have
attained to twenty years of age, a herring gull to forty-four, an
imperial eagle to fifty-six, a heron to sixty, an eagle owl to sixty-
eight, a raven to sixty-nine, a swan to seventy, and a goose to eighty.
Hobday 2 has recently described a pair of ring-doves which lived to

FIG. 188. — Land tortoise (Testudo maiiritanica), aged at least

eighty-six, belonging to M. Elie Metchnikoff.
(From Metchnikoff's The Prolongation of Life, by permission of Mr W. Heinemann.)

be twenty-one, and then did not die a natural death. Metchnikoff'
records a case of a parrot which lived for eighty-two years.

Mammals on the average appear to have considerably shorter
lives than birds. According to Weismann, whales live for some
hundreds of years, but it is difficult to see how this can be more than
an assumption. There can be little doubt that the great age assigned
by some of the older writers to elephants is mythical, and probably
150 years is almost the maximum ever attained. Horses in rare
cases have reached forty years, cattle somewhat over thirty, and
sheep over twenty years. A dog is said to have lived for thirty-four
years, but twenty is usually regarded as a great age for this animal.
Cats have been known to live to be twenty-one and even twenty-
three, but no greater ages appear to have been recorded. The white
rat may live forty months, or even longer, but the average age

1 Gurney, " On the Comparative Ages to which Birds Live," Ibi«, vol. v., 1899.

2 Hobday, " An Instance of Longevity in Bing-Doves," Vet. Jour., vol. Ixxvi.,
1920.

PHASES IN THE LIFE OF THE INDIVIDUAL 723

appears to be about thirty-four months.1 The white mouse is stated
to have a normal life .of two years, and this whether it has bred or
not, but females are slightly shorter lived than males.2

For man the traditional duration of life is seventy, but, as every
one knows, this age is very often much exceeded. Women on the
average live to be somewhat older than men.

Many instances are on record of extraordinary longevity, but
perhaps the most trustworthy is the famous case of Thomas Parr,
described by Harvey in the Philosophical Transactions of the Eoyal

FIG. 189. — Lonk sheep, aged eighteen years, with her last lamb. This sheep,
which belonged to Mr. William Peel of Knowlemere Manor, Clitheroe,
lived to be twenty-one years. It had thirty-five lambs, nine of which
were triplets.3

Society.4 His death is said to have been due to the change in his
mode of life, resulting from his migration from Shropshire to London,
" where he fed high and drunk plentifully of the best wines." " He
died after he had outlived nine princes, in the tenth year of 'the tenth
of them, at the age of one hundred and fifty-two years and nine
months." 5

1 Donaldson, loc. cit.

2 Kirkham, loc. cit.

3 I am indebted to my friend Mr. W. Ralph Peel, of Trinity College,
Cambridge, for this photograph (taken by his sister, Miss Peel), and for the
information which accompanied it.

4 Harvey, "Anatomical Account of Thomas Parr," Phil. Trans., vol. iii.,
1700. A portrait of Parr painted by van Dyck may be seen in the Royal
Gallery at Dresden.

5 For much further information about old age, longevity, etc., in man, see
Luciani, Human Physiology, vol. v., English Edition, London, 1921. See also Pearl,
" On the Mean Age at Death of Centenarians," Proc. Nat. Acad. ScL, vol. v., 1919.

724 THE PHYSIOLOGY OF REPRODUCTION

As to what factors determine the average duration of life in
different species is a problem about which there has been much
speculation. Weismann has elaborated a theory which asserts that
living matter was originally immortal, mortality first arising in
correlation with cellular differentiation. On this view the Protozoa
are potentially immortal,1 natural death occurring only among multi-
cellular organisms. The protoplasm of the latter is shown to be of
two kinds — germplasin, which is capable of propagating itself
indefinitely under suitable conditions like the protoplasm of unicellular
organisms, and somatoplasm, which composes the rest of the body
and is subject to natural death. The life of the somatic cells was at
first limited to one generation, but afterwards in the higher Metazoa
was extended to many generations, and the life of the organism was
lengthened to a corresponding degree. Such a restriction went on
hand in hand with a differentiation of the parts of the organism into
somatic and reproductive cells, in . accordance with the principle of
the physiological division of labour, and this process of differentiation
was controlled by natural selection. " Death itself," says Weismann,2
" and the longer or shorter duration of life both depend entirely on
adaptation. Death is not an essential attribute of living matter ; it
is neither necessarily associated with reproduction, nor a necessary
consequence of it." According to this theory, therefore, the
phenomena of senescence and death, as exhibited by all the cells
of the body with the exception of the germ-cells, are secondary
properties which have been preserved in multicellular organisms by
natural selection, because they are of direct advantage in the propaga-
tion of the species. An indefinite prolongation of*the life of the
organism after the age of reproduction had been passed would be of
no value or utility to the race, but rather a disadvantage, since it
would tend to retard the evolution of more perfectly adapted forms
of life. Furthermore, according to Weismann, longevity, although
depending ultimately upon the physiological properties of the cells,
is capable of adaptation to the conditions of existence, and consequently
is influenced by natural selection just in the same way as other
specific characters are.

Perhaps the most cogent criticism of Weismann's doctrine of
immortality is that of Verworn, who writes as follows: "The
conception of living substance as immortal will be accepted by
scarcely anyone who bears in mind the characteristic peculiarity
of living substance, viz., that it continually decomposes, or, in other
words, dies. There is no living substance that, so long as it is living

1 This question, about which there has been much controversy, is referred
to in Chapter VI. (pp. 220-224).

2 Weismann, "Life and Death," Essays, vol. i., 2nd Edition, Oxford, 1891.

PHASES IN THE LIFE OF THE INDIVIDUAL 725

at all, is not continually decomposing in some parts, while being
regenerated in others. No living molecule is spared this decom-
position. The latter, however, does not seize upon all molecules at
the same time; while one is decomposing, another is being
constructed, and so on. One living particle affords the conditions
for the origin of another or several others, but itself dies. The
particles newly formed in turn give rise to others and, likewise, die.
In this manner living substance is continually dying, without life
itself becoming extinct." x From this standpoint, therefore, there
can be no question of any kind of living substance being truly
immortal. The whole conception of a possible immortality arises
from a confusion of ideas.

Minot,2 on the other hand, has elaborated a theory of senescence
which may be regarded as an extension of that of Weismann.
Like the latter, he seems to assume that death is riot a universal
accompaniment of life, and that natural death lias been acquired
in the course of evolutionary development. He proceeds to define
senescence as an increase in the differentiation of the protoplasm.
During the early periods of life the young material is produced, and
the protoplasm is undifferentiated. During the later stages of
existence cell differentiation goes on, and the organism gradually
becomes old. When the cells acquire the faculty of passing beyond
the simple stage to the more complete organisation, they lose some-
thing of their vitality, of their power of growth, and of their
possibilities of perpetuation. Just as senescence depends upon
the increase and differentiation of the cytoplasm, so, conversely,
rejuvenation depends upon the increase of the nuclear material;
and consequently the alternation of the two phases of the life
cycle (the early brief one when the young material is formed, and
the later prolonged one when the process of differentiation is going
on) is due to an alternation in the proportions of nucleus and
protoplasm. In criticism of this theory, it may be urged that it is
in reality nothing more than a descriptive account of a general type
of cellular change, and that it provides no sort of explanation as to
why this type of change occurs, nor how it is that differentiation is
apparently correlated with a reduction of vitality leading eventually
to death.

Robertson and Ray3 have recently adduced evidence for the view
that the potential longevity of any given individual is determined
by the relative velocities of anabolism in the cellular and sclerou

1 Verworn, General Physiology, Lee's Translation from the second German
Edition, London, 1899.

2 Minot, loc. cit. For the views of Steinach, etc., on the interstitial gland,
see p. 327.

3 Robertson and Bay, loc. cit.

726 THE PHYSIOLOGY OF REPRODUCTION

tissues respectively. This hypothesis is based on a series of experi-
mental studies on the growth of the mouse under different conditions
(see p. 712).

Metchnikoff has laid great stress on the idea that natural death
is a rare phenomenon, at least among the higher animals. That
death with man is frequently, if not generally, caused by disease or
accident is a fact about which there can be no disagreement, and
Karl Pearson1 has worked out statistically the chances of death
occurring in the different phases of human life. "We have five
ages of man," he says, "corresponding to the periods of infancy,
childhood, youth, maturity or middle age, and senility or old age.
In each of these periods we see a perfectly chance distribution of
mortality centring at a given age and tacking off on either side
according to a perfectly clear mathematical law." It was found also
that the curve of mortality, as deduced from a study of the deaths
per annum of a thousand persons born in the same year, " starts
very high in infancy, falls to its least value at thirteen or fourteen
years with only 236 deaths. It then slowly increases till it reaches
a maximum in the seventy-second year of life, and falls more rapidly
than it rose, till scarcely two isolated stragglers of the thousand
reach ninety-one." It is clear, therefore, that death from old age
is far from being the rule in the human species, but, according to
Metchnikoff, it seldom occurs at all.2

This biologist found it impossible to accept the view that the high
mortality observable between the ages of seventy and seventy-live
indicates a natural limit to human life at about this period. Cen-
tenarians, he points out, are not really very rare, and he cites many
cases of extreme old age, including that of Thomas Parr referred to
above. Pteal old age, we are told, is associated with an instinct for
death which is as natural as is the instinct for sleep. Metchnikoff,
therefore, answers in an emphatic negative the question asked by
Admetus in Euripides' " Alcestis," " Is it the same thing for an old
man as for a young man to die ? " The fact that the instinct for
death seems so rarely to exist is regarded as evidence that true
senility is a comparatively infrequent phenomenon.

According to Metchuikoff, senescence is not brought about simply
as the result of arrest of the reproductive powers of the cells. The
whitening of hair in old age is due to the destructive action of
phagocytes which remove the pigment. Moreover, hairs become old
and white without ceasing to grow. Metchnikoff believed also that
atrophy of the brain is due to the destruction of the higher nerve-

1 Pearson, The Chances of Death, etc., vol. i., London, 1897.

2 Metchnikoff, loc. cit. ; and The Nature of Man, Mitchell's Translation,
London, 1903.

PHASES IN THE LIFE OF THE INDIVIDUAL 727

cells by neuronophags, and that there are many other devouring cells
which are adrift in the tissues of aged men and animals and cause
the destruction of other cells of the higher type. The testes, however,
appear to have the power to resist these phagocytes, and with this
power is correlated the fact that spermatozoa are often produced even
in advanced old age. Metchnikoff s theory as to the cause of death
is that it is due to the poisoning of the tissues and to th.e damage
done by phagocytes to those parts of the body affected by the toxic
action. He believed further that in man and certain of the animals
this process of poisoning is brought about by fermentation set up by
microbial action in the large intestine. The toxic substances produced
by the intestinal fermentation were supposed to enter the system and
poison it, the result being that the vitality of the tissues is lowered,
so that they are less able to resist the action of devouring phagocytes.
The presence of lactic acid in the intestine was believed to arrest the
process of fermentation. Metchnikoff recommended, therefore, the
regular drinking of sour milk as a means of destroying the microbes
in the intestine in the hope of prolonging life.

The term " Death " is employed in two separate senses ; it may
mean the death of the whole body, i.e. somatic death (this being
the sense in which it is ordinarily used), or it may be applied to the
death of the individual tissues, some of which remain alive for many
hours after the body as a wrhole is said to be dead. The death of
the body as a whole usually occurs suddenly. As Michael Foster
says : " Were the animal frame not the complicated machine we
have seen it to be, death might come as a simple and gradual dis-
solution, the ' sans everything ' being the last stage of the successive
loss of fundamental powers. As it is, however, death is always more
or less violent; the machine comes to an end by reason of the
disorder caused by the breaking down of one of its parts. Life
ceases not because the molecular powers of the whole body slacken
and are lost, but because a weakness in one or other part of the
machinery throws its whole working out of gear." l

The synchronous disturbance of two or more of the bodily
functions, such as is wont to occur in old age, may destroy that
co-ordination of the various vital activities without which life
cannot continue. The stoppage of the heart's beat is the ordinary
criterion of death, and this is a true conception, because the cessation
of the heart's movements implies the arrest of the circulation of the
blood and the consequent starvation of the tissues of the body.

The tissues do not die simultaneously, for, as already described,
some cells of the body are in process of disintegration through the
whole of life. After somatic death, the cells which make up the

1 Foster, Text-book of Physiology, Part IV., 5th Edition, London, 1891.

728 THE PHYSIOLOGY OF REPRODUCTION

nervous system usually die very rapidly. The same is true of
the gland-cells; but the muscles may remain sensitive to external
influences for many hours. In animals it has been shown that the
heart itself after removal from the body, if kept under suitable
conditions and perfused with an artificial fluid resembling blood-serum,
may continue to live and undergo rhythmical contractions for a
considerable time. In the process of death-stiffening, or rigor mortis,
the muscles once more contract spontaneously, and not till this has
happened is their life utterly extinguished. Rigor mortis is brought
about by the coagulation of the muscle plasma within the cells. It
begins at periods varying from half an hour to thirty hours after
somatic death, and it continues for an average of about thirty hours.
Certain cells may even live for some time after rigor mortis has passed.
This is notably the case with the ciliated epithelial cells of the inner
surface of the respiratory passages, and with the white corpuscles of
the blood. Sooner or later, however, every part of the organism
perishes, putrefactive changes set in, and the entire substance of the
body passes once more to that " dust " out of which its vital activities
enabled it to build itself up in the progress of individual life.

SUBJECT INDEX

Abortion, 563 ; in in- breeding, 218 ; and
ovariotomy, 366 ; and corpus luteum,
366 sq. ; and iron, 548 ; puerperium
after, 584 sq. • caused by male parent,
637 ; frequency of, in man, 650 sq. ;
frequency of, in sheep, 651, 656 ;
frequency of, in cattle, 651 ; frequency
of, in horses, 652 ; by ergot, ib. ; by
oil of juniper, ib. ; by yew, ib. ; by
turpentine, ib. ; by camphor, ib. ;
by cantharides, ib. ; by aloes, ib. ; by
Callicarpa, 652 ; by mechanical means,
ib. ; causes of, in man, ib. sq. ; time of,
in horses, 653 sq. ; causes of, in cow,
654 ; by superpurgation, ib. ; epizootic
abortion, 654 sq. ; causes of, in sheep,
655

Abraxas grossulariata, sex-linked char-
acteristics in, 676

Abraxas lacticolor, sex-linked character-
istics in, 676

Absorption spectrum of luteins, 274

Abutilon, self-sterility of, 215

Accessory reproductive organs of the
male, Chapter VII., passim

Acetone bodies, in pregnancy, 535 sq. ;
excretion of, 544 ; in urine of preg-
nancy, 544

Acetonuria during pregnancy, 545

Achrosome, 166

Acid-base equilibrium during pregnancy,
536, 545 sqq.

Acidosis of pregnancy, 545 sqq.

Acmcea, parthenogenesis in, 234

Acomys caharinus, yolk-sac in, 423

Actinia mesembryanthemum, breeding
season in, 8 ; longevity in, 721

Adenine, 307, 309

" After-pains " of parturition, 579

Age, effect of, on fertility, 626 sq. ; influ-
ence of, on sex determination, 684, see
also Longevity

Ageniaspis fuscicollis, polyembryony in,
679

Alanine, 288, 304

Albatross, mating habits of, 25

Albinism, 203 ,

Albumen, 286 sq. ; composition of, in egg,
288 ; metabolism of, in placenta, 506 ;
in colostrum, 595, 619

Albuminaria, 544 ; in pregnancy, 536 ;
in puerperium, 583

Alcoholism, effect of, on germ cells, 209 ;
sterility due to, in rats, 647

Alcyonium digitatum, breeding season in, 8

Allantoidean trophoblast of hedgehog,
480

Allantoidean trophspongia of hedgehog,
481

Allantoin, 309

Allantois, of Dasyurus, 417 ; of dog, 421 ;
of mouse, 470 ; of primates, 490 ;
origin of, 411 ; 413 sq.

Allelomorphism, 201

Allopterotism in aves, 341 sqq.

Aloes, abortion by, 652

Alveoli of mammary gland, 589

Alytes, effects of castration in, 338

Amenorrhcsa, 69, 133 n. ; ovarian treat-
ment of, 355

Amia, breeding season of, 16

" Ammonia index," 532

Ammonia coefficient, 532 sq.

Ammonia excretion during pregnancy, 546

Amnion, 412, 414; formation of, 413;
of rabbit, ib. ; of bat, 490 ??. ; of
Murinus, ib.

Amphibia, breeding season in, 18 sqq. ;
formation of corpus luteum in, 145 ;
fertilisation in, 182 ; polyspermy in,
185 ; sex-determination in, 663

Amphimixis, 210

Amphioxus lanceolatus, breeding season
in, 15 ; maturation of ova in, 129

Ampulla of Henle, 240 ; in horse, ib. ;
in sheep, ib.

Amylase in placenta, 465

Amyloid bodies, 300

Anasa tristis, dimorphism of spermatozoa
in, 672 ; sex-determination in, ib.

Anemone, breeding season in, 8

Anguis, formation of corpus luteum in,
145

Angioplasmode, 445 sq., 456 ; of dog, 446

Annelida, breeding season in, 9 ; matura-
tion of ova in, 128 sq.

Ancestrum, 32 sq. ; in carnivora, 92

Anopheles, egg-formation in, 12

Antilocapra americana, phenomena as-
sociated with breeding in, 25 ; effects
of castration in, 322, see also Prong-
buck

Aphidae, parthenogenesis in, 230

Aphis, breeding season in, 10

Aphrodiasias, 638 sq.

Arbacia, movements of spermatozoa in,
172 ; water content of ovum of, 185 ;
sperm-agglutination in, 186 ; oxidation
process in ovum of, 187 sq. ; life cycle
in, 227 ; parthenogenesis in, 231 sq., 314

730

SUBJECT INDEX

Arbacia pustuhsa, chemistry of sperma-
tozoa of, 306

Area vasculosa, 412, 415

Arenicola, development of, 227

Arginine, 288, 304 sq., 306, 309, 312

Armidillo, polyembrony in, 229

Arrhenoplasm, 690

Artery during senescence, 718

Arthropoda, breeding season in, 10 sqq. ;
effects of castration in, 325 sq.

Artificial fertilisation, 185, 194, 227 sq.,
313

Artificial insemination, see Insemination

Artificial parthenogenesis, 185, 194, 230
sqq., 313, 317 sq.

Arvicola, clitoris in, 261

Arvicola agrestis, cestrous cycle in, 37

Arvicola glareolus, cestrous cycle in, 37

Ascaris, maturation of ova in, 125

Ash, composition of, in pup, 595 ; in
milk of dog, ib. ; in serum of dog, ib.

Ass, source of foetal iron in, 434

Assortive mating, among gametes, 214 sq.;
in Paramcecium, 221

Astacus fluviatilis, see Crayfish

Asterias, maturation of ova in, 129 n. ;
fertilisation in, 194 sq., 235 sq. ; hy-
bridisation of, 212 ; life cycle in, 227

Asterias forbesii, parthenogenesis in, 231
sq.

Aslerina, fertilisation in, 235

Atretic follicle, 149 sqq.

Atrophic foetuses, 154, see Foetal atrophy

Aves, allopterotism in, 340 sq. ; ovari-
otomy in, 341 sqq. See also Birds

Axis, oestrous cycle in, 45

Axolotl, breeding season in, 20 ; poly-
spermy in, 183 ; fertility in, under
experiment, 631

B

Baboon, menstrual process in, 57 sq.

Baby, respiratory quotient of, 505

Badger, cestrous cycle in, 54 n. ; period
of gestation in, ib. ; placenta, 448

" Banchstiel " of primates, 490

Bandicoot, see Perameles

Balcenoptera musculus, breeding season in,
48

Barasingha, cestrous cycle in, 43 sq.

" Barotaxis," 172

Barrenness, in sheep, 633. See also
Sterility

Bartholin's gland, effect of cestrous on,
51 ; secretion of, 264, 268

Bat, cestrous cycle in, 56 ; dormant
spermatozoa in, ib. ; maturation of ova
in, 127 sq. ; ovulation in, 131 sq. ;
spermatozoa in, 169 ; fertilisation in,
183 ; yolk-sac in, 425 ; trophoblast of,
487, 489 ; plasmodiblast of, ib. ; cyto-
blast of, ib. ; placenta of, 487 sqq. ;

couche paraplacentaire of, 487 sqq. ;
phagocytosis in, 488 ; somatopleur of,
489 ; splanchnopleur of, 489 ; amnion
of, 490 w. ; placental haemopoiesis, 518 ;
size of litters in, 624 sq. See also
Vesperugo noctula

" Bausteine," 463

Bear, cestrous cycle in, 53 ; period of
gestation in, ib. ; fertility in, 626 ;
course of sterility in, 629

Beaver, preplacental blastocyst of, 423 ;
placenta of, 475 sq. ; " Haftstiel " of,
475 ; megalokaryocytes of, 475 ; tro-
phoblast of, 476 '

Bees, sex-determination in, 664 sqq. ;
hybridisation in, 666 ; longevity in, 721

Belgium, birth-rate in, 660

Bibos frontalis, hybridisation of, with
Bison americanus, 641

Bibos gaums, hybridisation of, with Bibos
grunnicus, 641

Bibos grunnicus, hybridisation of, with
Bibos gaurus, 641

Biochemistry of sexual organs, 273 sqq.

Birds, breeding season in, 4, 21 sqq. ;
migration of, 22 sq. ; formation of
corpus luteum in, 145 ; biochemistry of
sexual organs in, 276 ; secondary sexual
characteristics of, under captivity, 629 ;
sterility in, ib. sq. ; sex determination
in, 678 ; longevity in, 722. See al-so
Aves

Birth, cause of, 573 sqq. ; growth of body
before, 703 sq. ; growth of body after,
705 sqq.

Birth-rate, of man, 658 sqq. ; in England
and Wales, 659 ; decline in, 659 sq. ;
cause of decline in, ib. ; in British
colonies, 659 sq. ; in France, 660 ; in
Germany, ib. ; in Belgium, ib.

Bison, oestrous cycle in, 43 sqq.

Bison americanus, hybridisation of Bibos
frontalis and, 641

Bison bonasus, hybridisation of cow and,
642

Bison frontalis, 641

Blastocyst, 405, 407 ; of sheep, 421 ; of
pig, 427 ; of guinea-pig, 472 sq. ; of
hedgehog, 476 ; of shrew, 481 ; of
mole, 484 ; of Tupaia javanica, 485 ;
of man, 493, 496, 498; fixation of,
508 sqq.

Blastodermic vesicle, 407, 411 ; of rabbit,
422 sq., 453 ; of horse, 429 ; of sheep,
430

Blastomere, 407

Blood, pressure of, during menstruation,
63; coagulation of, during menstruation,
ib. ; effect of castration on, 392 ; in
uterine milk, 434 sq. ; composition of,
during pregnancy, 540, 542, 556 sq.

Bobolink, phenomena associated with
breeding in, 27

Body-weight during pregnancy, 523 sq.

Bolina hydatina, dissogonie in, 228 n.

SUBJECT INDEX

Bombyx mori, composition of eggs of,
292 sq. ; parthenogenesis in, 230

Bone during senescence, 718

Bonellia, sex-differentiation in, 692

Bordure verte of placenta, 447

Bos indicus, hybridisation of, with Bos
taunts, 641

Bos taurus, hybridisation of, with Bos
indicus, 641

" Bottcher's crystals," 299, 300

" Bouchon vaginal," 245

Boules, 404

Bradypus, placenta of, 409, 442

Brain, weight of at different ages, 719 ;
cells of in senescence, 719 sq.

Breeding, periodicity in, 10, 13, 28 sqq. ;
phenomena associated with, 24 sqq. ;
in snipe, 25 ; in lark, ib. ; in albatross,
ib. ; in cock-of -the-rock, ib. ; in Cervus,
ib. ; in Antilocapra, ib. ; in salmon, 26 ;
in Polypterus, ib. ; in Lepidosiren, ib. ;
in dragonet, ib. ; in Cyclopterus lumpus,
27 ; in lyre-bird, ib. ; in phalarope,
ib. ; in pelican, ib. ; in bustard, ib. ;
in linnet, ib. ; in salmon, ib. ; in Oncho-
rhynchus, ib. ; in tanager, ib. ; in
bobolink, ib. ; in swiftlets, 28 ; in
stickle-back, ib. ; in snake, ib. ; in
crocodiles, ib. ; in tortoise, ib.

Breeding season, Chapter I., passim ; in
cat, 4 ; in wolf, ib. ; in fox, ib. ; in
birds, ib. ; in fishes, ib. ; in insects,
ib. ; in Protozoa, 5 sq. ; in Coelenterata,
6 sqq. ; in Hydra orientalis, 6 sq. ; in
Hydra viridis, 1 ; in Sagartia troglodytes,
8 ; in Actinia mesembryanthemum, ib. ;
in Xenia hicksoni, ib. ; in Alcyonium
digitatum, ib. ; in Sarcophytum, ib. ;
in Holophytum, ib. ; in Sclerophytum,
ib. ; in Ctenophora, 9 ; in Nemertea,
ib. ; in Stychostemma asensorialum, ib. ;
in Diplozoon paradoxum, ib. ; in Anne-
lida, ib. ; in Palolo worms, ib. sq. ; in
Eunice fucata, 10 ; in Eunice viridis,
ib. ; in Astacus fluviatilis, ib. ; in
Periphatus, ib. ; in Aphis, ib. ; in
Ceratocephale osawai, ib. ; in Poly-
chaetes, ib. ; in Nereis limbata, ib. n. ;
in Qdontosyllis eopla, ib. ; in Arthro-
poda, 10 sqq. ; in Cryptorhynchus gravis,
12 ; in Patella, ib.; in Pur pur a
lapillus, ib. ; in Buccinum undatum,
ib. ; in Mollusca, 12 sqq. ; in Littorina,
12, 14 ; in pond-snails, 13 ; in land-
snails, ib. ; in Tergipes, 14 ; in sea-
urchin, ib. ; in Echinodermata, ib. ;
in starfish, ib. ; in Echinus microtuber-
culatus, ib. ; in Echinus acutus, ib. ;
in Echinus esculentus, ib. ; in Diadema
serosum, ib. sq. ; in Cephalochordata,
15 ; in Amphioxus lanceolatus, ib. ;
in Elasmobranchs, ib. ; in Teleosts, ib. ;
in cod, ib. ; in fishes, ib. sqq. ; in
plaice, 16 ; in Lepidosteus, ib. ; in
Amia, ib. ; in Dipnoi, ib. ; in Polypterus

' bichir, ib. ; in Polypterus senegalis, ib. ;
in Polypterus lapradii, ib. ; in Cerato-
dus, ib. ; in Lepidosiren, ib. ; in Pro-
topterus, ib. ; in eel, 17 ; in salmon,
ib. ; in tree-frog, 18 ; in toad, ib. ; in
frog, ib. sqq. ; in Amphibia, 18 sqq. ; in
Xenopus Icevis, 19 ; in Xenopus, ib. sq.;
in Discoglossus, 20 ; in Axolotls, ib. ; in
Triton waltlii, ib. ; in Rhacophorus leuco-
mystax, ib. ; in Rana limnocharis, ib. ;
in newt, 21 ; in salamander, ib. ; in
Reptilia, ib. ; in Aves, ib. sqq. ; in fowl,
ib. ; in sparrow, 22 ; in sanderling,
ib. ; in Cereopsis, 22 n. ; in swifts, 23 ;
in Mammalia, 24 ; in camel, ib. ; in
sheep, ib. ; development of secondary
• sexual characters during, 25 ; origin of,
30 ; factors influencing frequency of, 31 ;
in opossum, 36 ; in Didelphys aurita,
ib. ; in Trichosurus vulpecula, ib. ;
in Macropus ruficollis, ib. ; in Mus
rattus, 37 ; in Lepus cuniculus, 37 ;
in whale, 47 sq. ; in Balfenoptera
musculus, 48 ; in rorquals, ib. ; in
dolphin, ib. ; in Canis azarce, 50 ; in
fox, ib. ; in Lycaon pictus, ib. ; in cat,
51 ; in wild cat, 52 ; in hedgehog, 55 ;
in Semnopithecus entellus, 54 ; in
Macacus rhesus, 57 sq. ; in Cercocebus,
57 ; evidence of primitive, in man, 64
sqq. ; in Mammalia, 365 sq.

British colonies, birth-rate in, 659 sq.

Brunst, see Heat, period of

Buccinum undatum, breeding season in, 12

Bufo, hybridisation in, 210

Bulbo - cavernosus muscle, 254, 262,
266 sqq.

Bulbo-urethral gland, 51

" Biirstenbesatz," 397 sq.

Burrhel sheep, see Ovis burrhel

Bustard, phenomena associated with
breeding in, 27

Butyrin in milk, 594

Calcium, excretion of, during menstruation,
63 ; in egg of fowl, 278 ; metabolism of,
298, 389 ; during pregnancy, 519, 547,
550 ; in foetus of man, 547 ; in milk,
594 ; in ash of pup, 595 ; in milk of
dog, ib. ; in serum of dog, ib.

Callicarpa, abortion by, 652

Callionymus lyra, phenomena associated
with breeding in, 26

Caloric value of egg, 285

Calotes jubatus, egg-membrane in, 289

Camel, breeding season in, 24 ; cestrous
cycle in, 45 ; period of gestation in, ib.

Camphor, abortion caused by, 652

Canary, fertility in, 629 ; sex-linked
characteristics in, 677 ; longevity in,
722

Canidse, fertility in, 629

732

SUBJECT INDEX

Canis, hybridisation in, 641

Canis agarce, breeding season in, 50

Cantharides, effect of, on genital organs,
638 ; abortion by means of, 652

Cape hunting dog, see Lycaon pictus

Capronin in milk, 594

Captivity, effect of, on fertility, 628 sqq. •
on Emberiza passerina, 629 ; on linnet,
ib. ; on pyrrhula, ib. ; on oriole, ib. ;
on Falco albidus, ib. ; on parrot, 630 ;
on hawk, ib. ; on chetah, ib. ; on ele-
phant, ib.

Caput gallinaginis, 242

Carbohydrate, in ovum, 463 ; absorption
of, by maternal organism, 537 ; of
maternal organism, 537 sq. ; require- j
ment of foetus, 538 sq. ; excretion of, |
during pregnancy, 539 sqq. ; import-
ance of, in foetus of rodents, 545 ; in
milk, 594

Carbon dioxide in milk, 595

Carcinus mcenas, glycogen in, 295

Carnivora, oestrous cycle in, 48 sqq. •
oestrus in, 92 ; anoestrum in, ib.
procestrum in, ib. ; uterine cycle in
92 sqq. ; placenta of, 408, 410, 442 sqq.
mesoblast of, 420 ; yolk-sac in, ib.
glycogen storage in, 538 ; puerperium
in, 584 ; teat of, 587 ; fertility in, 629

Carotin, 273

Carp, longevity in, 722

Casein in milk, 594

Caseinogen, in milk, 594 ; in colostrum,
595, 619 ; formation of, in milk, 601

Castration, effect of, on vesiculae, 246 ;
effect of, on prostate gland, 251 ; effect
of, on Cowper's glands, 252 ; effect
of, on erection, 271 ; effects of,
320 sqq. ; prostate gland after, 320 ;
Cowper's glands after, ib. ; effect of,
on larynx, 321 ; effect of, in stag, ib. ;
effect of, in fallow deer, ib. ; effects of,
in Antilocapra americana, 322 ; effect
of, in cattle, ib. sq. ; effect of, in man,
321, 323 ; effect of, in guinea-pig, ib. ;
effect of, in fowl, 321, 334 sq., 699 ;
effect of, in sheep, ib. ; effect of, in
horse, 325 ; effect of, in arthropods,
ib. sq. ; effect of, in Ocneria dispar, ib. ;
effect of, in silkworm, ib. ; effect of, in
crickets, ib. sq. ; effect of, in duck, 336 ;
effect of, in Alytes, 338 ; effect of, on
thymus, 379 ; effect of, on pituitary
gland, 381 ; effect of, on suprarenals,
386; effects of, on metabolism, 388
sqq. ; effect of, on respiratory exchange,
389 sq. ; effect of, on blood, 392 ; and
uterine involution, 582 ; and lactation,
614 ; effect of, during pregnancy in
guinea-pig, 620

Cat, 269 ; breeding season in, 4, 51 ;
period of gestation in, 51, 442 ; oestrous
cycle in, 51 ; ovary of, 109 ; ovulation
in, 131 ; follicular atresia in, 151 ;
superfoetation in, 154 ; syncytium of,

444 sq. ; placenta of, ib. sqq. ; vital
staining in, 466 ; ductless glands during
pregnancy in, 538 ; origin of foetal fat
in, 543 ; lumbar nerves of, 560 ; ute-
rine contraction in, 562 ; mechanism
of parturition in, 571 ; fertility in,
628 ; foetal atrophy in, 656 ; puberty
in, 714 ; menopause in, 717 ; longevity
in, 722

Caterpillars, artificial hermaphroditism in,
325

Catharsis, 535

Cattle, heat during gestation in, 33 ??. ;
oestrous cycle in, 43 ; period of gesta-
tion in, ib. ; ovulation in, 131 ; artificial
insemination in, 175, 649 ; hybrid of,
with bison, 211, 642 ; penis in, 261 ;
effect of castration in, 322 sq. ; ovari-
otomy in, 344, 346 ; yolk-sac in, 420 ;
placenta in, 429, 432 sq., 435 ; chorionic
sac of, 432 ; inter-cotyledonary tropho-
blast of, ib. ; Isevulose in foetus of, 537 ;
prolonged gestation in, 578 ; udder of,
586 ; mammary glands of, ib. ; milk of,
594 ; milking capacity of, 596 ; dura-
tion of lactation in, 599 sq. ; fertility
in, 627 ; sterility in, 631 sq., 641, 646 ;
causes of abortion in, 654 ; foetal
atrophy in, 656 ; sex-determination in,
668 ; growth of, 706 sqq. ; puberty in,
714. See also Bos taurus

Cause of birth, theories of, 573 sqq.

Cavia porcellus, oestrous cycle in, 38 ;
period of gestation in, ib. sq.

Cell division, 702 ; factors controlling,
ib.

Cells of Sertoli, 162 sq.

Centetes, number of mammary glands in,
586

Centetes ecaudatus, placenta of, 486 sq.

Centric placenta! attachment, 442

Centrosome, 109 n., 180 sqq.

Cephalochordata, breeding season in, 15

Ceratodus, breeding season of, 16

Ceratocephale osawai, breeding season in,
10

Cercocebus, breeding season in, 57 ;
oestrous cycle in, 58 ; menstrual cycle
in, 90 sq.

Cercopithecus, cestrous cycle in, 58 ;
mammary secretion by virgin of, 615

Cercopithecus cynosurus, period of gesta-
tion in, 59

Cerebrosides in corpus luteum, 274

Cero-psis, breeding season in, 22

Cervix, 72

Cervix uteri, involution of, 582

Cervus, placenta of, 432

Cervus alces, vesicula seminalis of, 245

Cervus elaphus, mating habits of, 25

Cetacea, cestrous cycle in, 47 sq. ; dis-
charge of ova into Fallopian tube in,
135 ; placenta of, 408, 410, 442 ; posi-
tion of mammary gland in, 586 ; teat
of, 587

SUBJECT INDEX

733

Chacma baboon, see Papio porcarius

Charcot-Leyden crystals, 299

Chatopterus, parthenogenesis in, 230, 233

Cheiroptera, placenta of, 408, 410, 487
sqq. ; position of mammary glands in,
586 ; size of litters in, 624

Chemistry, of corpus luteum, 273 of
ovum, 276 sqq. ; of semen, 296 ; of
spermatozoa, 302 sq.

Chemotaxis of spermatozoa, 224 ; of
ferns, 224 ; of Fucacese, 224 sq.

Chermes, conditions of sexual reproduction
in, 11

Chetah in captivity, 630

Chironomus, paedogenesis in, 228 n.

Chitin, 294 ; source of, 294

CMamydomonas as diet for Hydatina, 668

Chloride in pregnancy, 551 sq. ; retention
of, 552

Chlorine in egg of fowl, 278 ; in foetus of
man, 547 ; in ash of pup, 595 ; in
milk of dog, ib. ; in serum of dog, ib.

Chlorosis, 365, ovarian treatment of, 355

Cholaepus, placenta of, 442

Cholesterin, 310 ; in corpus luteum, 274
sq. ; in ovary, 274 sq. ; in egg of fowl,
277, 279, 282 ; in eggs of herring, 290 ;
in eggs of insects, 293 ; synthesia of,
294 ; in semen, 297 ; in spermatozoa,
302 sq. ; in tails of spermatozoa, 311 ;
in blood of pregnancy, 542 ; in milk, 594

Cholesterinesters in blood of pregnancy,
542

Cholesterol, 392 ; as prolonging life, 712

Choline, 292, 299, 301 sq., 392

Chorion, 412, 414; of pig, 427; of
primates, ib.

Chorionepitheliomata, 368

Chorionic sac of cow, 432

Chromosomes, 199, 319 ; number of,
in man, 120 ; in maturation, 125 sq. ;
hereditary nature of, 199 ; as basis of
heredity, 204, sqq. ; in Protozoa, 205 ;
in Coslenterates, ib. ; in Cyclops, ib. ;
in Crepidula, ib. ; in Cryptobranchus,
ib. ; in Echinus, 206 ; in Menidia, ib. ;
in Pundulus, ib. ; in Ctenolabras, ib. ;
in Vicia, ib. ; number of, in Galgulus
oculatus, 673 ; number of, in Lygceus
bicrucis, ib. ; number of, in horse, 678 n.

Ciona intestinalis, self-sterility of, 215 ;
self -fertility of, 216

Circulation in pregnancy, 557

Climate, influence of, on milk, 596 sqq.

Clitoris, 74, 261, 267; in Rodentia, 261; in
Tupaia, 261 ; in Arvicola, 261 ; in Talpa,
261 ; in Stenops, 261 ; in Hyena crocuta,
261 sq. ; innervation of, 560

Clupeine, in spermatozoa, 303 ; constitu-
tion of, 305

" Clupeovin" in eggs of herring, 290 sq.

Coagulating gland, 248, 300 sq.

Cock-of-the-rock, mating habits of, 25

Cockroach, movements of spermatozoa of,
171

Cod, breeding season of, 15

Ccelenterata, breeding season in, 6 sqq. ;
struggle for existence among ova in, 120
n. ; fertilisation in, 183 ; chromosomes
in, 205 ; hermaphroditism in, 688

Ccelom, extra-embryonic, 412

Cold-spots of penis, 254

Collocalia, phenomena associated with
breeding in, 28

Colloids, in regard to ovariotomy, 385

Colostrum, composition of, 559, 595 ;
compared with milk, 595 ; caseinogen
in, 595, 619 ; albumen in, 595, 619 ;
globulin in, 595, 619; fat of, 619;
lactose of, ib. ; proteose of, ib.

Colpoda steini, conditions of conjugation
in, 6 ; 222 sq.

Compacta of man, 498 sq.

Conalbumen in white of egg, 287

Conjugation, as a source of variation, 198 ;
in Infusoria, 205 ; in Protozoa, 220 sqq. ;
in Ciliates, 220 sq. ; maturation in,
220 ; in Paramoscium caudatum, 220
sq. ; and rejuvenescence, 222 ; in
Stylonychia, 221 ; in Colpoda steini,
222 sq.

Connecting stalk of yolk-sac, 425

Contraction of uterus, Chapter XII.

Contra-deciduate placenta, 409

Copulation, effect of excess of, on fertility,
637

Copulatory organ, 253 sqq.

Cornua uteri, 71

Corona radiata, 404 sqq.

Corpus albicans, formation of, 149

Corpus cavernosum, 253, 255

Corpus luteum, 111, 114 n., 363, 388, 515 ;
hypotheses of, 137 sq. ; formation of,
ib. sqq. ; of mouse, 138 sqq. ; of
rabbit, 139, 143 sq., 149; of Tarsius,
139, 145 ; of Tupaia, 139, 145 ; of
Sorex, 139, 145 ; of man, 140 ; of
sheep, 141 sq., 146 ; of Vesperugo, 142,
145 ; of Vespertilio, 142 ; of Placotus,
ib. ; of marsupial cat, 142 sq., 145 ; of
pig, 144 ; of guinea-pig, ib. sq. ; of
lower vertebrates, 145 ; of Ovis, ib. ;
of Mus, ib. ; of Lepus, ib. ; of Sper-
mophilus, 145 ; of Myliobatis, ib. ;
of Zoarces, ib. ; of birds, ib. ; of Am-
phibia, ib. ; of Anguis, ib. ; of Seps,
ib. ; of Mammalia, 146 ; of Cyclo-
stomes, ib. ; of Teleosteans, ib. ; of
fowl, ib. ; during pregnancy, 148 sq. ;
of pseudo-pregnancy, 149, 576, 616 sq.,
619 ; of lactation, 149, 621 sq. ;
lipochromes of, 273 ; luteins of, ib. ;
hsematoidin of, ib. ; cerebrosides in,
274 ; lecithin in, ib. sq. ; phosphatides
in, ib. ; lipoids in, ib. ; cholesterin in,
ib. sq. ; fat in, ib. ; in hedgehog,
365; function of, 365 sqq., 387; in
Dasyurus viverrinus, 366 ; and abor-
tion, ib. sq. ; as organ of internal

734

SUBJECT INDEX

secretion, 367 ; in non-placental Mam-
mals, ib. ; in Dasyurus, 367, 372 sq. ;
in Perameles, 367 ; in polyoestrous
animals, 373 ; in moncestrous animals,
ib. ; sterility caused by persistence of,
374 ; extract of, 391 ; and toxaemias
of pregnancy, 392 ; as controlling
factor in lactation, 616 sqq. ; during
second half of pregnancy, 619 ; of rat,
620 ; extract of, as galactogogue, 621 ;
of Dasyurus, 622 ; of rat, ib.

Corpus luteum atreticum, 150

Corpus luteum spurium, 373

Corpus spongiosum, 241, 253, 259

Corpus uteri, 71

Cotyledonary burrs, 429 sq.

Cotyledonary papillae, 71

Couche paraplacentaire of bat, 487 sqq.

Coussinets of placenta, 452

Cowper's glands, 268, 300 ; position of,
251 ; glands of Littre of, ib. ; secretion
of, 251 sq. ; after castration, 252, 320

Crab, form of spermatozoa in, 169 ;
effects of Sacculina on, 326 ; effects of
Peltogaster on, ib.

Crayfish, breeding season in, 10

Creatin, composition of, 288 ; metabolism
of, in placenta, 506 ; in urine, 533 ; in
urine of pregnancy, 536

Creatinine, metabolism of, in placenta, 506

Cremaster muscle, 164 n., 165

Grepidula, chromosomes in, 205

Crepidula fornicata, sex -reversal in, 692

Crepidula plana, sex-reversal in, 692

Crested grebe, mating habit of, 690

Crickets, effects of castration in, 325 sq.

Crista urethra, 242, 268

Crocodile, phenomena associated with
breeding in, 28 ; longevity in, 722

Crocodilus biporcatus, egg-membrane in,
289

Cross-breeding, effect of, on fertility, 218,
639

Cross-fertilisation, 210 ; in Mammalia,
211 ; in Echinoderms, ib.

Cross-sterility, 210, 215

Crustacea, pigments in eggs of, 294 sqq. ;
lutein in, 295 sq. ; sex-determination in,
666 ; hermaphroditism in, 688

Cryptobranchus, chromosomes in, 205

Cryptorchids, 164 n.

Cryptorchism, 164 n. ; artificial, 332

Crypts of uterine mucosa, 442

Cryptorhynchus gravis, breeding season in,
12

Ctendrilus monostylos, reproduction in,
226

Ctenolabrus, chromosomes in, 206

Ctenophora, breeding season of, 9

Cuckoo, atrophy of ovaries in, 22

Culex, 12 n.

Cumulate placenta, 410

Cuttlefish, composition of egg covering in,
292 sq.

Cyclops, chromosomes in, 205

Cyclopterus lumpus, phenomena associated

with breeding in, 27
Cyclostomes, corpus luteum in, 146
Cynthia, fertilisation in, 190
Cynthia partita, self -fertility in, 215
Cyprinine, 305
Cystin, 277, 305, 551
Cystine, 288, 304, 308 sq.
Cytolysins, 316
Cytolysis, 314 sqq.
Cytoblast, of shrew, 482 ; of mole, 484 ;

of Tupaia javanica, 486 ; of bat,

487
Cytoplasm, ratio of, to nuclear material,

702, sq.
" Cytoplasmic inheritance," 207

Dacus, sexual attraction in, 12
Daphnia, parthenogenesis in, 670
Dasypus, placenta of, 442
Dasyurus, breeding habit of, 67 ; f ollicular

atresia in, 153 sq. ; corpus luteum in,

367, 372 sq., 622 ; allantois of, 417 ;

foetal membranes of, 418 ; period of

gestation in, ib. ; commencement of

lactation in, 615
Dasyurus viverrinus, 418 ; oestrous cycle

in, 36 ; period of gestation in, ib. ;

corpus luteum in, 142 sq., 145, 366 ;

pseudo-pregnancy in, after spontaneous

ovulation, 616 sq.
Datura, sex-determination in, 675
Death, cause of, Chapter XVI. ; meaning

of, 727 ; order of, in tissues, ib. sq.
Death's-Head hawk moth, sterility of,

in England, 11
Decidua, 400 sqq. ; nature of, 403 ; of

man, 497, 499 ; expulsion of remains

of, 581
Decidua capsularis, of Pteropus edulis,

489 ; of primates, 491
Decidual cavity of mouse, 468 sq.
Decidual cells, 99 ; of man, 502
Deciduata, classification of, 408 ; placenta

of, 442 sqq. ; fcetal nutrition in, 510

sqq. ; puerperium in, 584
Decidua serotina, 370 ; of man, 493,

502

Deciduofracts of hedgehog, 479, 481
Deciduomata, 374

Deer, 321 ; mating habits of, 25 ; perio-
dicity in breeding in, 30 ; oestrous

cycle in, 43 sq. ; ovariotomy in, 340 ;

prochorion of, 406 ; source of fcetal

iron in, 434
Dementia prsecox, 310
Dermographismus, 559
Desamidase ferment, 507
Descent of testis, 164 n., 165 ; cases of

absence of, 165

SUBJECT INDEX

735

Destruction period, in menstrual cycle of
man, 78 sqq. ; in menstrual cycle of
monkeys, 85 sqq. ; in uterine cycle of
Carnivora, 94 sq. ; in uterine cycle of
Ungulata, 104

" Detrituszone " of man, 496

Determinants, 198 sq.

Determination of sex, 11. See also Sex
determination

Deutobroque cells, in ougenesis, 116, 118

Deutoplasm, 404

Development, of Loligo, 191 ; of Nereis,

227 ; of Arenicola, 227
Dextrin in milk, 514

Diadema serosum, breeding season in,

14 sq.

Dictyate stage of ougenesis, 117, 155
Didelphys aurita, cestrous cycle in, 36 ;

breeding season in, ib.
Didelphys virginiana, see Opossum
Didermic blastocyst, 412
Diet, influence of, on milk, 596 sqq.
Dimorphism of gametes, 672
Dinophilus, fertilisation in, 184
Dinophilus apatris, dimorphism of ova in,

679
Dicestrous cycle, 34 ; number of, in sheep,

ib. ; number of, in Rodents, ib.
Dicestrum, 34

Diplotenic stage of oiigenesis, 117, 155
Diplo-trophoblast, 412, 476 sq.
Diplozoiin paradoxum, breeding season in,

9

Dipnoi, breeding season in, 16
Dipodillus simoni, O3strous cycle in, 37

sq. ; prolonged gestation in, 578
Dipodillus campestris, cestrous cycle in, 37
Discoid placenta, 408
Discoglossus, breeding season in, 20
Discus proligerus, 121, 123; in dog, 110;

in rabbit, 124
Dissogonie, 228 ; in Bolina hydatina,

228 n. ; in Eucharis multicornis, 228 n.
Dog, period of gestation in, 30 ; heat

during gestation in, 33 n. ; cestrous
cycle in, 48 sqq. ; period of gestation
in, 50 ; uterine cycle in, 92 sq. ; pseudo-
pregnancy in, 97, 102 ; uterine mucosa
in, 99, 102, 443 ; ovary of, 110 ; theca
interna of, ib. ; discus proligerus in,
ib. ; theca external of, ib. ; interstitial
cells in ovary of, 120 n. ; discharge of
ova into Fallopian tube in, 136; artificial
insemination in, 174 sq., 649 ; in-breeding
in, 218 sq. ; prostate gland in, 248 ;
composition of semen in, 297 ; effect
of ovarian extract upon, 350 ; ovari-
otomy in, 361, 391 ; factors determining
heat in, 364 ; ovariotomy during preg-
nancy in, 369 ; thymectomy in, 380 ;
effect of pituitary extract on, 383 ;
hypophysectomy in, ib ; prochorion of,
406 ; yolk-sac in, 421 ; allantois of,
421 ; period of gestation in, 442 ;
source of foetal fat in, 450 ; syncytium

of, 444 sq. ; placenta of, ib. sqq. 5
angioplasmode of, 446 ; foetal nutrition
in, 456 ; simplasma in, 457 ; metabol-
ism during pregnancy in, 524 sq. ; nitro-
gen balance during pregnancy in, 526
sqq. ; nitrogen excretion in, 532 ;
glycogen storage in, 537 ; origin of
fcetal fat in, 543 ; calcium during
pregnancy in, 550 ; phosphorus meta-
bolism during pregnancy in, ib. ;
energy metabolism in pregnancy in, ib. ;
blood of, during pregnancy, 556 ;
mechanism of parturition in, 571 ;
pseudo-pregnancy in, 576 ; milk of,
595 ; composition of ash of pup, ib. ;
composition of ash of milk of, ib. ;
composition of ash of serum of, ib. ;
corpus luteum of pseudo-pregnancy in,
617 ; explanation of lactation by
virgin of, ib. ; fertility in, 626, 628 ;
foetal atrophy in, 656 ; puberty in,
714; longevity in, 722

Dolphin, breeding season in, 48 ; period of
gestation in, ib.

Domestication, effect of, on fowl, 24 ;
fertility under, 628

Donkey, ovulation in, 131 ; artificial in-
semination in, 175

" Dotterplattchen," 291

" Double monsters," sex of, in man, 679

Dove, see Pigeon and Ring-dove

Dragonet, phenomena associated with
breeding in, 26 sq.

Drosophila, sterility in, 641 ; sex-deter-
mination in, 674

Drosophila ampelophila, in- breeding in,
217 ; sex-linked characteristics in, 675
sq.

Drugs, effect of, on fertility, 638 sq.

Duck, effect of castration in, 336 sq. ;
ovariotomy in, 343 sqq. ; fertility in,
630

Ductless glands, correlation of, with
generative organs, 379 sqq. ; in preg-
nancy, 558 sq.

Duct of Gartner, 71

Dugong, placenta of, 409

Dysmenorrhcea, definition of, 61 ; cause
of, 80

Dyspepsia in menopause, 715

Eagle, longevity in, 722
Earthworm, polyspermy in, 183
Echidna, cestrous cycle in, 35 ; gestation
period in, 36 ; mammary glands of, 587
Echinodermata, breeding season in, 14
sq. ; fertilisation in, 183 ; cross-
fertilisation in, 211 ; parthenogenesis
in, 230 sq.

Echinoidea, movements of spermatozoa
in, 171 ; hybridisation in, 219 sq.

736

SUBJECT INDEX

Echinus, movements of spermatozoa of,
172 sq. ; fertilisation in, 182 ; chromo-
somes in, 206 ; fertility in crosses of,
211 ; sterility in crosses of, ib.

Echinus acutus, breeding season in, 14 ;
hybridisation in, 211 sq.

Echinus esculentus, breeding season in,
14; hybridisation of, 211 sq.

Echinus microtuberculatus, 315 ; breeding
season in, 14 ; oxidation in ovum of,
192

Echinus miliaris, oxidation in ovum of,
197 ; hybridisation of, 211 sqq.

Eclampsia, 533 sqq., 544

Ectoderm, 402, 406

Ectopic pregnancy, 136 sq., 368

Ectoplacental cone of mouse, 467

Ectoplacenta of rabbit, 453 sq.

Edentata, placenta of, 409 sq., 442

Eel, breeding season of, 17 ; sexual
activity in, 21

Egg, respiratory quotient during develop-
ment of, 284 ; caloric value of, 285.
See also Ovum

Egg formation, see Oogenesis

Egg-membrane, in Raja, 289 ; in- Scyl-
lium, ib. ; in Tropidonatus, ib. ; in
Calotes jubatus, ib. ; in Crocodilus
biforcatus, ib. ; in Mustelus ICKVIS, ib. ;
in frog, 290 ; in perch, ib. ; mucin in,
ib.

Egg-shell, composition of, 276 sqq.

" Eikammer," of mouse, 467, 470 ; of
man, 499

Ejaculation mechanism, 262 sqq., 270

Eland, O3strous cycle in, 45

Elastin, 289

•Elasmobranchs, breeding season in, 15

Elephant, periodicity of breeding in, 29 ;
O3strous cycle in, 47 ; period of gesta-
tion in, ib. ; temporal gland of, 253 ;
yolk-sac in, 421 ; position of mammary
gland in, 586 ; sterility in Indian, 628 ;
under captivity, 630 ; longevity in, 722

Eliomys quercinus, cestrous cycle in, 37

Elk, fertility in, 626

Emberiza passerina in captivity, 629

Embryo, mucin in, 287, 463 ; of opossum,
417 ; of man, 426, 500 ; of shrew, 483 ;
provision of nutriment for, 521 sq.

Embryonic knot, 412 n.

Embryonic shield of Ungulata, 420

" Embryotrophe," 436, 444

End-bulbs of penis, 254

Endo-enzymes, 289

Endometrium, 72

Endomixis, in Paramoecium, 223

End-organs of penis, 254

" Energy of development," 285, 293

Energy metabolism during pregnancy,
552 sqq.

Energy requirement, during sexual rest,
519 ; during first pregnancy, ib. ;
during second pregnancy, ib. ; of foetus,
525

England and Wales, birth-rate in, 659

" Entwicklungsarbeit," 363

Environment, effect of changed, 222 sq.

Enzymes, 289

Eosinophil cell, 96 sq.

Epididymis, 160, 268

Epididymitis as cause of sterility, 645

Epizootic abortion, 654 sq.

Epoophoron, 71

Erectile tissue of penis, 256 sq.

Erection, mechanism of, 262 sqq. ; nerve

centre for, 264 sq. ; by nervi srigentes,

265 ; by sacral nerves, 266
Erector clitoridis, 267
Erepsin in placenta, 465
Erinaceus, foetal membranes of, 425
Erinaceus europeus, see Hedgehog
Ersatz-zellen, 402
Erythrocytes, 458
Erythrotoxin, 549

Eucharis multicarnis, dissogonie in, 228 n.
Eunice viridis, breeding season in, 10
Eunice fucata, breeding season in, 10
Eunuch, 321 n., 323, 328
Eutheria, procestrum in, 107
Excentric placental attachment, 442
Excretion, of urea, 532 sq. ; of acetone

bodies, 544
Exogamy, 217 n.
" Extractives " in semen, 297
Extra-uterine growth, 703
Extra-uterine pregnancy, development of

mammary gland during, 611

Faeroes Islands, breeding season of
anemones in, 8

Falco albidus in captivity, 629

Fallopian tube, structure of, 70 sqq.

Fallow-deer, cestrous cycle in, 44 ; effect
of castration on, 322

False amnion, 412, 414

Fat, in corpus luteum, 274 sq. ; in ovary,
275 ; in egg of fowl, 277 ; oxidation
of, 284; in tails of spermatozoa, 311 ;
in uterine milk, 435 ; in foetus, 458 ;
metabolism of, in placenta, 458 sqq.,
471 sq., 475, 503 sq. ; metabolism of,
in mouse, 471 sq. ; in guinea-pig, 475;
metabolism of, in placenta of man, 503,
sq. ; metabolism of, in f oatal organs, 504 ;
metabolism of, during pregnancy, 541
sqq., 544 sq. ; absorption of, by maternal
organism, 541 ; of maternal organism,
541 sq. ; requirement of foetus, 542 sq. •
"»• -origin of, in foetus, 543 sq. ; in milk, 594,
604 ; formation of, in milk, 601 q. ;
of colostrum, 619

Fatness, sterility caused by, 632

FeKda?, fertility in, 629

Feminisation of guinea-pig, 697 sq.

SUBJECT INDEX

737

Ferments, 289 ; of foetal blood, 465 ; con-
tent of placenta, 465 sq., 507 sq., 516
sq. .; proteolytic, 507 ; lipolytic, ib. ;
oxidation, ib. ; desamidase, ib. ; oxi-
dases, ib. ; glycolytic, ib. See also
Enzyme

Ferret, cestrous cycle in, 53 ; period of
gestation in, ib. ; uterine cycle in, 92
sq. ; formation of corpus luteum in,
144 ; maturation of ova in, 130 ;
ovulation in, 130, 134 ; discharge of
ova into Fallopian tube in, 136 ;
oestrus in, 364 ; prochorion of, 406 ;
placenta of, 448 ; fertility in, 628 ;
fcetal atrophy in, 656

Fertility, 215, Chapter XIV., passim;
of bull- bison hybrid, 211 ; in Echinus
crosses, 211 ib. ; and in-breeding, 216
sqq. ; in cross-breeding, 218 ; in man,
626 ; in sheep, 626, -627 sq., 632 sqq. ;
in dog, 626, 628 ; in bear, 626 ; in
elk, ib. ; • effect of age on, ib. sq. ; in
guinea-pig, 627, 635 sq. ; in rabbit, 627
sq., 636 ; in cattle, 627 ; in fowl, ib. ;
in pig, ib. sq., 636 ; effect of environ-
ment and nutrition on, ib. sqq. ; under
domestication, 628 ; in cat, ib. ; in
ferret, ib. ; in Gallus bankiva, ib. ; in
wild duck, ib. ; in turkey, ib. ; in
goose, ib. ; in pigeon, ib. ; in pea-fowl,
ib. ; in plants, ib. ; in Suidae, ib. ;
in Ruminants, 629 ; in Carnivora, i
ib. ; in Canidae, ib. ; in Felidae, ib. ;
in Rodentia, ib. ; in monkey, ib. ; I
in canary, ib. ; in gull, ib. ; in ostrich, '
630 ; in duck, ib. ; in plantigrades,
ib. ; in axolotls under experiment, 631 ; :
effect of food on, in sheep, 634 ; share
of ram in, of sheep, 635 ; influence of
male on, 636 sq. ; effect of excessive i
copulation on, 637 ; effect of prolonged
lactation on, ib. sq. ; effect of drugs
on, 638 sq. ; effect of in-breeding and
cross-breeding on, 639 sq. ; of hybrids, ;
641 ; of lion-jaguar hybrid, ib. ; of
geese hybrids, ib. ; of Canis hybrids, ib.;
of Bovidae hybrids, 641 ; of Bos <
hybrids, ib. ; of Bibos hybrids, ib. ;
of Bison- Bibos hybrids, ib. ; inherit-
ance of, 642 sqq. ; inheritance of, in
sheep, ib. ; inheritance of, in man,
643 ; inheritance of, in horse, ib. ; •
inheritance of, in pig, ib. ; inheritance !
of, in mice, ib. ; inheritance of, in fowl,
ib. sq. ; influence of abortion on, 650
sqq. ; problem of increase of, 657 sq. ; ,
in man, 658 sqq.

Fertilisation, Chapter VI., passim ; in
Mammalia, 182 ; in Echinus, ib. ; in
Amphibia, ib. ; in Pisces, ib. ; in
Insecta, ib. ; in Echinodermata, 183 ;
in Coelenterata, ib. ; in bat, ib. ; in
Histribodella, 184; in Dinophilus, ib. ;
in Saccocirrus, 184, 193 ; in Turbellaria,
184; artificial, 185, 194, 230, 313; in

24

Nereis, 186 ; oxidation process of,
186 sq., 187 ; in Rana fusca, 187 ;
in Stronglocentrotus, 194 sq. ; in Cynthia,
190 ; in Asterias, 194 sq. ; hereditary
effects of, 197 sqq. ; conditions favour-
able for, 210 ; artificial aids to, 229 ;
nature of, 234 sqq. ; in Aster ina, 235 ;
in Asterias, 235 sq. ; in sea-urchin, 236 ;
in Lottia, ib. ; in Polynoe, ib. ; bio-
chemistry of, 313 sqq. ; ovum after,
405 sqq. ; movements of ova after,
407 ; effect of, on sex-determination,
666 sqq.

Fertilisin, 317

Fetid toad, oviposition in, 135

Fibrin, 395 sq.

" Fibrinstreif en " of man, 502

Filiform process of penis, 259 sqq.

Finch, form of spermatozoa in, 169

Fire- bellied toad, oviposition in, 135

Fish, breeding season in,- 4, 15 sqq. ;
fertilisation in, 182; artificial impregna-
tion in, 176 ; polyspermy in, 183 ;
hybridisation of, 213 sq. ; biochemistry
of sexual organs in, 289 ; composition
of eggs of, 290 ; longevity in, 722. See
also Pisces

Florence's reaction, 301

" Florence's reagent," 299

Flowering plants, development of, 7 n.

Flushing, practice of, in sheep, 41, 634 sq.

Flying fox, see Pteropus

Fly larvae, sex-determination in, 664

Fcetal atrophy, 636, 656 sq.

Fcetal nutrition and the placenta,
Chapter X., passim.

Fcetal membranes, Chapter X., Part 3

Foetus, villi of, in sheep, 431 ; source of
fat of, 450, 458 ; glycogen in, 462,
538 sq., 553 ; absorption of oxygen by,
464 sq. ; ferments of blood of, 465 ;
respiration of, in man, 504 sq. ; energy
requirement of, 525 ; carbohydrate
requirement of, 538 sq. ; origin of fat
of, 543 ; ash constituents of, in man,

547 ; synthesis of haemoglobin in,

548 ; respiratory quotient of, 552 sq.
Follicular atresia, in man, 147 ; in guinea-
pig, 151 ; in cat, ib. ; in rabbit, 149,
151, 153, 154 ; in sparrow, 152 sq. ;
corpus luteum in, 153 sq. ; in Dasyurus,
ib.

Follicle cells, 113, 119

Food, influence of, on sex-determination,
662 sqq.

Fowl, breeding season in, 21 sq. ; effect
of domestication on, 24 ; ovulation in,
134 n. ; formation of corpus luteum in,
146 ; polyspermy in, 183 ; Mendelism
in, 200 ; transplantation of ovary of,
209, 343 ; protein in egg of, 277 ;
sugar in egg of, ib. ; cholesterin in egg
of, 277, 279, 282 ; fat in egg of, 277 ;
lecithin in egg of, 277, 279 sq., 282;
chlorine in egg of, 278 ; potash in egg

738

SUBJECT INDEX

of, ib. ; sodium in egg of, ib. ; calcium
in egg of, ib. ; magnesium in egg of, ib. ;
iron in egg of, ib. sq. ; phosphorised fats
in egg of, 279 ; luteins in egg of, 281 ;
phosphorus in egg of, 278, 282 ;
livetin in egg of, 283, 286; effect of
castration in, 323 sq., 334 sqq. ; fostal
intersexuality in, 339 ; ovariotomy in,
341 sqq. ; thymectomy in, 380 ; fertility
in, 627 ; inheritance of fertility in,
643 sq. ; sex linked characteristics in,
677 ; hermaphroditism in, 689 n., 693
sq. ; intersexuality in, 695 ; effects of
castration in, 699 ; effects of ovariotomy
in, ib. ; growth of, 706, 708, 711

Fox, breeding season in, 4, 50 ; period of
gestation in, 50

Fox-hounds, in- breeding in, 216

France, birth-rate in, 660 ; sex-ratio in,
687

" Free-martin,"' 689, 694 sq.

Frog, breeding season in, 18 sqq. ; matura-
tion of ova in, 128 ; polar body in, ib. ;
discharge of ova into oviduct in, 136 ;
form of spermatozoa in, 169 ; artificial
impregnation in, 176 ; hybridisation
in, 210 ; life cycle in, 227 sq. ; partheno-
genesis in, 234, 316 ; egg- membrane in,
290 ; ranovin in egg of, 291 ; ferment
of gonads of, 318 ; internal secretion
of testes in, 337 sq. ; transplantation
of testes in, ib. ; " summer cells " of,
385 ; sex-determination in, 662 sq., 668 ;
sex-reversal in, 693

Fruit-fly, sexual attraction in, 12

Fundulus, chromosomes in, 206 ; life
cycle in, 227

Fur seal, cestrous cycle in, 54

Gadus aiglefinus, chemistry of spermatozoa

of, 308
Gadus morrhua, chemistry of spermatozoa

of, 305
Galactogogue, 597, 604 ; corpus luteum

extract as, 621

Galactophorous sinuses of udder, 586
Galeopitheci, placenta of, 409
Galeopithecus volans, uterine cycle in, 92
Galago agisymbanus, placenta of, 428, 440
Galgulus oculatus, sex-determination in,

673 ; dimorphism of spermatozoa in,

ib. ; number of chromosomes in, ib.
Gallus bankiva, fertility in, 628
Gametes, assertive mating among, 210,

214 sq. ; reduction of vitality of, 220 ;

sex-determination by, 671 sq. See also

Ova and Spermatozoa
Gaseous metabolism, 390
Gasteropoda, maturation of ova in, 128
Gaur, see Bibos gaurus, 641
Gayal, cestrous cycle in, 45. See also

Bibos frontalis

Gazdlu dorcas, cestrous cycle in. 45

Gazelle, 259

Geese, hybridisation in, 641

" Gewebspilz," of man, 493

Genera, sterility between, 640

Generative organs, innervation of, in
female, Chapter XII. ; effect of aphro-
disias on, 638

Genito-crural nerve, 270

Gerbillus hertipes, cestrous cycle in, 37

Germany, birth-rate in, 660

Germ-cells, effect of alcohol on, 209 ;
effect of lead on, ib. ; effect of X-rays
on, ib. ; effect of external conditions
on, 208 sqq. ; effect of soma on, 208 sqq.
See also Gametes

Germinal layers, inversion of, in mouse,
468 ; inversion of, in guinea-pig, 473

Germinal spot, 109. See Nucleolus

Germinal vesicle, 109. See Nucleus

Gestation, heat during, 33 re. ; sac of
rabbit, 452 ; duration of, 577 sq. ;
prolonged, 577 sqq. ; prolonged, in
horse, 578 ; prolonged, in cow, ib. ;
prolonged, in Dipodillus simoni, ib. ;
prolonged, in man, ib. ; prolonged, in
Meriones shawi, ib. ; prolonged, in
Meriones longifrons, ib. ; in Mus muscu-
lus, ib. ; prolonged, in mice, ib. sq.

Gestation period, 29 sqq. ; in dog, 30 ;
in seal, ib. ; in Echidna, 35 ; in
Marsupialia, ib. sq. ; in Marsupial cat,
36 ; in Dasyurus viverrinus, ib. ; in
Mus decumanus, 37 ; in Mus rattus,
ib. ; in Cavia porcellus, ib. sq. ; in
cattle, 43 ; in roe-deer, 43 n. sq. ; in
camel, 45 ; in walrus, ib. ; in pig, 46,
68 n. ; in horse, 46 ; in elephant, 47 ;
in dolphin, 48 ; in dog, 50, 442 ; in
wolf, 50 ; in fox, ib. ; in Lycaon
pictus, ib. ; in cat, 51, 442 ; in wild
cat, 52 ; in lion, 53 ; in tiger, ib. ;
in puma, ib. ; in bear, ib. ; in ferret,
ib. ; in polecat, ib. ; in badger, 54 n. ;
in walrus, 55 ; in hedgehog, ib ; in
Macacus, 59 ; in Macacus nemesfrinus,
ib. ; in Cercopithecus cynosurus, ib. ;
factors influencing duration of, 68 ;
in Southdown sheep, ib. ; in Merino
sheep, ib. ; in opossum, 417 sq. ;
in Dasyurus, 418 ; in Perameles, 419 ;
in rabbit, 456 ; size of litters in relation
to, 624

Giant- cells of mouse, 469 sq.

Gigantism, 323

Giraffe, cestrous cycle in, 45 : penis of,
259 ; placenta of, 432

Glands of Bartholini, 253

Glands of Duverney, 253

Glands of Morgagni, 251

Glands of Skene, 242

Glans penis, 254, 260 sq.

Globulins, 286 sq. ; of colostrum, 595,
619

Glucoprotein in white of egg, 287

SUBJECT INDEX

739

Glucosamine, 287 ; from human ovary,

276 ; in ovum, 463
Glucose metabolism, effect of hyper-

glycaemia on, 463

Glutathione, oxidation in ovum of, 197
Glycine, 288, 304

Glycerinesters in blood of pregnancy, 542
Glycogen, 286, 294 ; in egg of Bombyx,
293 ; in Carcinus moenas, 295 ; in
plaques amniotiques, 436 ; metabolism
of, in placenta, 460 sqq., 471, 475, 503 ;
in placenta of rabbit, 460 sqq, ; in
foetus, 462 ; metabolism of, in mouse,
471 ; metabolism of, in guinea-pig, 475 ;
metabolism of, in placenta of man, 503 ;
distribution of, in foetus, 553 ; storage
of, in dog, 537 ; storage of, in guinea-
pig, ib. ; storage of, in man, ib. sq. ;
in placenta of Ruminants, 538 ; in
placenta of Rodentia, ib. ; in placenta
of Carnivora, ib. ; in placenta of man,
ib. ; in foetus, 538 sq. ; requirement of
fcetus, 539

Glycolytic ferments, 507
Glycosuria, 539 sqq., 602 sq. ; in puer-

perium, 583

Gna, cestrous cycle in, 45
Goat, oestrous cycle in, 43 ; in- breeding in,
224 ; uterus masculinus in, 242 ;
formation of lactose in, 602 sq. ; lacta-
tion before parturition in, 615 ; galacto-
gogue effect of corpus luteum extract
in, 621 ; size of litters in, 623 ; foetal
atrophy in, 656 ; hermaphroditism in,
695

Goitre, 384
" Gonadin," 363

Gonads, transplantation of, 331 sqq.
Goose, fertility in, 628 ; longevity in, 722
Granular vaginitis, sterility due to con-
tagious, 646

Graphian follicle, 110 sq., 122, 404;
rupture of, 133 sq. ; atresia of, 149 sqq.
" Green border " of placenta, 447
" Green pockets " of placenta, 447
Growth, in Protozoa, 701 ; amount and
time ratio of, 703 ; intra-uterine, ib. ;
extra-uterine, ib. ; of body before birth, ;
ib. sq. ; of body after birth, 705 sqq. ;
of guinea-pig, 705 ; of rabbit, 706, ,
708; of chicken, 706, 708, 711; of j
horse, 706, 711 ; of cattle, 706 sqq. ; \
of sheep, 707 sqq. ; of pig, 707 ; of
man, 709 sqq. ; internal factors control-
ling, 712 ; of mice, 712 ; of vocal
cords, 713

Growth period, in menstrual cycle of man,
75 sqq. ; in menstrual cycle of monkeys,
85 ; in uterine cycle of Carnivora,
93 sq. ; in uterine cycle of Ungulata,
103 sq.

Oryllus campestris, 326
Guanidin, composition of, 289
Guanine, 307, 309
Gubernaculum, 164 n.

Guinea-pig, uterine cycle in, 101 sq. •
pseudo-pregnancy in, 103 ; maturation
of ova in, 127 ; ovulation in, 130 ;
oestrous cycle in, 134 n. ; formation of
corpus luteum in, 144 sq. ; follicular
atresia in, 151 ; spermatotoxic serum in,
164 n. sq. ; artificial insemination in,
176 ; transplantation of ovary of, 209,
346, 620, 696 sq. ; vesicula seminalis
of, 240 ; effect of castration in, 323 ;
interstitial cells of testes in, 330 ;
transplantation of testes in, 331 sq. ;
artificial cryptorchism in, 332 ; ovari-
otomy in, 346, 350 ; effect of ovarian
extract on, 356 ; thymectomy in, 379 ;
pulpe diffluente of, 432 ; placenta of,
451, 472 sq. ; respiratory quotient in,
465 ; vital staining in, 466 ; implanta-
tion cavity of, 472 sqq. ; blastocyst of,.
472 sq. ; symplasma of, 473 ; inversion
of germinal layers in, ib. ; glycogen
metabolism in, 475 ; fat metabolism in,
ib. ; size of offspring in, 522 ; meta-
bolism during pregnancy in, 524 ;
glycogen, storage of, in, 537 ; origin of
foetal fat in, 543 ; respiratory quotient
of foetus of, 552 sq. ; number of mam-
mary glands in, 586 ; formation of"
lactose in, 603 ; connection between
mammary and foetal growth in, 609 sq. ;
correlation of mammary glands with
generative organs in, 619 sq. ; effect
of castration during pregnancy in, 620 ;
fertility in, 627, 635 sq. ; fcetal atrophy
in, 656 ; masculinisation of, 696 ;
feminisation of, 697 sq. ; growth of, 705.
See also Cavia porcellus

Gull, fertility in, 629 ; longevity in, 722

Gum in milk, 594

Gusterosteus spinachia, phenomena as-
sociated with breeding in, 28

Gymnura, placenta of, 409. See also
Malayan hedgehog

Gynandromorph, anterior-posterior, 689 n.

H

Haematogen, 283

Hsematoidin in corpus luteum, 273
Haemoglobin, 434; in development of

chick, 283; absorption of,, by tropho-

blast, 464 ; synthesis of, in fcetus, 548
Haemoglobinsemia, in pregnancy, 549
Haemolysis, 559
Haemopoiesis in placenta, 518
" Haftflecke " of Tupaia javanica, 485 «gv
" Haftstiel," of Tarsius, 423 ; of monkey,.

ib. ; of man, 423, 494, 500 ; of beaver,.

475 ; of Primates, 490
" Haftzotten," of man, 501
" Halbplacenta," 409
Halicore, placenta of, 442
Hamster, perineal gland in, 253 ; inguinal

gland in, ib. ; preputial gland in, ib. ; .

foetal atrophy in, 656

740

SUBJECT INDEX

Hare, size of litter in, 625

Harp seal, cestrous cycle in, 54

Hawk, sterility in, 629 ; in captivity, 630

Heart, during pregnancy in rat, 557 ;

during senescence, 718
Heat period, 33, 562 ; during gestation,
33 n. ; relation of, to menstruation,
107 ; factors determining, 358 sqq. ;
absence of, after ovariotomy, 361 ;
after ovarian transplantation, 361 ;
ovarian extract causing, 362 ; factors
determining, in dog, 364
Heat-spots of penis, 254
Hedgehog, breeding season in, 55 ; period
of gestation in, ib. ; vesiculae seminales
in, ib. n. ; interstitial cells of testes in,
163 ; vesicula seminalis of, 244 sq. ;
corpus luteum in, 365 ; placenta of,
409, 476 sqq. ; yolk-sac in, 424 ;
zona pellucida of, 476 ; blastocyst of,
ib. ; trophoblast of, ib. sqq. ; diplo-
trophoblast of, ib. ; trophospongia of,
478 sq. ; trophosphere of, 478 ; ovum
of, ib. ; deciduofracts of, 479, 481 ;
omphaloidean region in, 480 ; allan-
toidean trophoblast of, ib. ; allan-
toidean trophospongia of, 481
Helicine arteries of penis, 255
Hemiptera, longevity in, 721
Hemitragus jeruldicus, cestrous cycle in,

43 sq.
Heredity, and fertilisation, 197 sq. ; and

chromosomes, 199, 204 sqq.
Hermaphroditism, 688 sqq. ; artificial, in
caterpillars, 325 ; complete, 688 ; in
sponges, ib. ; in Ccelenterates, ib. ;
in Mollusca, ib. ; in Crustacea, ib. ;
in Mammalia, 689 ; partial, ib. ; in fowl,
ib. n. ; in Rhizocephala, 692 ; in fowl,
693 ; in pheasant, 694 ; in pig, 695 ;
in goat, ib.
Hermit crab, parasitic castration in, 326 ;

intersexuality in, 691
Heron, longevity in, 722
Herring, 17 ; phosphorised fats in eggs of,
290 ; keratin in eggs of, ib. ; clupeovin
in eggs of, ib. sq. ; cholesterin in eggs of,
290

Heteroplastic graft of ovary, 350 sqq.
Heterozygote, 674
Heterozygosis, 641
Hexoses, 282
Hibernation, 21
Hippomanes, 413, 437
Hippopotamus, oestrous cycle in, 46
Histamine, 392
Histidine, 288, 304, 309
Histone, 305 sq.

Histriboddla, fertilisation in, 184
Holophytum, breeding season of, 8
Homoplastic graft of ovary, 351 sqq.
Homosexuality, 691
Homozygote, 673

Homozygosity, in- breeding and, 217 sq.
Hormone of ovary, 577

Horse, heat during gestation in, 33 n. ;
cestrous cycle in, 46 sq. ; period of
gestation in, 46 ; ovulation in, 131 ;
artificial insemination in, 175, 178,
648 sq. ; sterility in, 216 ; in-breeding
in, ib. ; rejuvenescence in, 223 sq. ;
ampulla of Henle in, 240 ; composition
of semen in, 297 ; effects of castration
in, 325 ; foetal membranes of, 413 ;
yolk-sac in, 420 ; placenta of, 428 sq. ;
blastodermic vesicle of, 429 ; tropho-
blast of, ib. • source of foetal iron in,
434 ; parturition in, 568 sq. ; pro-
longed gestation in, 578 ; growth of
mammary gland in, 606 ; sterility due
to overfeeding in, 631 ; sterility of
hybrid with zebra, 642 ; inheritance of
fertility in, 643 ; causes of sterility in,
646 ; abortion in, 653 sq. • foetal
atrophy in, 656 ; sterility in, 658 ;
dimorphism of spermatozoa in, 678 n. ;
number of chromosomes in, ib. ;
growth of, 706, 710 ; puberty in, 714 ;
menopause in, 717 ; senescence in, 721 ;
longevity in, 722
Horse-breeding, 216

Hybridisation, 199 ; sterility caused by,
210 ; in frog, ib. ; in Triton alpestris,
ib. • in Pelodytes, ib. ; in Bufo, ib. ; of
cattle and bison, 211 ; in Strongylo-
centrotus, 212 sq. ; in Echinus acutus,
211 sq. ; in Echinus miliaris, 211 sqq. ;
in Echinus esculentus, 211 sq. ; in
Aster ias, 212 ; in Myiilus, 213 ; in
fishes, ib. ; in Echinoids, 219; of lion
with jaguar, 641 ; in geese, ib. ; in
Canis, ib. ; of Bos taurus and Bos
indicus, ib. ; of Bibos grunnicus and
Bibos gaurus, ib. ; of Bibos frontalis
and Bison americanus, 641 ; of cow
and Bison bonasus, 642 ; of horse
and zebra, ib.; of bee, 666. See also
Mendelism
Hydatina, sex-determination in, 667 ;

influence of food on, 668
Hydatina senta, sex-determination in, 668 ;
parthenogenesis in, 670 ; dimorphism
of ova in, 679

Hydrsemia of pregnancy, 556
Hydra orientalis, reproduction of, 6 sq
Hydroids, alternation of generations in

marine, 7

Hydrometra during menopause, 715
Hydrops graviditatis, 552
Hyena crocuta, clitoris in, 261 sq.
Hylomys, see Malayan hedgehog
Hymen, 71 sq., 582

Hymenoptera, sex-determination in, 667
Hypercholesterinaemia in maternal or-
ganism, 542
Hyperglycaemia, during pregnancy, 462 ;

effect of, on glucose metabolism, 463
Hyperlactation in man, 600
Hypernephromata, 385
Hyperpituitarism, 383 sq.

SUBJECT INDEX

Hypertrophy, of ovary, 357 sq. ; of uterine

mucosa, 370

Hypoblast, 412, 414 ; of man, 493
Hypogastric nerves, 267 sqq.
Hypophysectomy in dog, 383
Hypoxanthine, 307
Hyrax, yolk-sac in, 421 ; placenta in,

450 sq.
Hysterectomy, 376 sqq. ; in rabbit, 348 ;

effect of, on ovary, 377 sqq.
Hysteria in menopause, 715

I

Ibex, cestrous cycle in, 43 sq.

Ichthulin, 290 sqq. : source of, in ovary,
292

Idioplasm, 690

Ids, 199, 201

Immortality of Protozoa, 724

Implantation cavity, of mouse, 468 sqq. ;
of guinea-pig, 472 sqq. ; in man, 493,
497

Impotence, causes of, 644 sq.

Impregnation, 174 ; artificial, 176 ; in
frog, ib. ; in newt, ib. ; in fish, ib.

Inachus, sex-metabolism in, 691

In-breeding, effects of, 215 sqq. ; in horses,
216 ; in fox-hounds, ib. ; in pigs,
ib. ; and fertility, ib. sqq. ; and
sterility, ib. sqq. ; in mice, 217 ; in
rats, ib. ; in Drosophila ampelophila,
ib. ; in maize, ib. ; and homozygosity,
ib. sq. ; and abortion, 218 ; in sheep,
ib. ; in dogs, ib. sq. ; and virility
of spermatozoa, 219 ; and vitality of
ova, ib. sq. ; in rabbits, 224 ; in goats,
ib. ; effect of, on sterility, 639 ; effect
of, on fertility, ib. sq.

Incubation period, 23

Indeciduata, placenta of, 427 sqq.

Indian ink, for vital staining, 466

Infarct formation, 575

Infusoria, conjugation in, 205

Inguinal canal, 164

Inguinal gland, 253 ; in musk deer, ib. ;
in musk rat, ib. ; in hamster, ib.

Innervation, of female generative organs,
Chapter XII. ; of external female
generative organs, 560 sq. ; of clitoris,
560 ; of vulva, ib. ; of ovaries, 561 ;
of uterus, ib. sqq. ; of vagina, ib.

Impotence, phosphorus as cure for, 638 ;
strychnine as cure for, ib. ; yohimbine
as cure for, ib.

Insecta, fertilisation in, 182 ; polyspermy
in, 183 ; cholesterin in eggs of, 293 ;
phosphorised fats in eggs of, 293 ;
longevity in, 721

Jnsectivora, oestrous cycle in, 55 sq. ;
uterine cycle in, 92 ; placenta of, 408,
410, 476 sqq., 509 ; yolk-sac in, 424 sq.

Insemination by artificial means, 131, 174
sqq. ; in dog, 174 sq., 649 ; method of,

174 sq., 648 sqq. ; in horse, 175, 178, 648
sq. ; in donkey, 175 ; in cattle, 175,
649 ; in rabbit, 176 ; in guinea-pig, ib. ;
in mouse, 176, 649 ; in man, 176,
647

Intersexuality, in fowl, 339 ; in Ruticilla
phoenicurus, 341 ; in pigeon, 686 ; in
Hermit crab, 691 ; in Ophryotrocha
puerilis, 692 ; in pigeon, 694 ; in
Lymantria crosses, ib. ; in fowl, 695

Interstitial cells, 155 sq., 339 ; of ovary,
119, 142 n., 144 ».; 145, 147, 346 sq.,
386 n. ; origin of, in mole, 120 n. ;
origin of, in stoat, ib. ; origin of, in
dog, ib. ; of testes, 160 sq., 163, 335 sq. ;
of ovary, during gestation, 376

Interstitial placenta! attachment, 442

Intervillous spaces of placenta, 395

Intra-uterine growth, 703

Intromittent sac of penis, 258

Invertebrata, chemistry of ova of, 292 sqq.

Involution, of vagina, 582 ; of cervix uteri,
ib. ; of uterus, 581

Ischio-cavernosus muscles, 254, 262, 266,
268

Iron, in egg of fowl, 278 sq. ; source of,
in ova, 292 ; in spermatozoa, 311 ; as
catalyst, 315 ; source of foetal, 434,
547 sq. ; metabolism of, in placenta,
457 sq., 505 sq. ; granules of, in placenta,
459 ; in foetus of man, 547 ; in preg-
nancy, ib. sqq. ; in placenta, ib. ; in
foetal organs, 505 sq., 548 ; and abor-
tion, ib. ; in milk, 594 ; in ash of pup,
595 ; in milk of dog, ib. ; in serum of
dog, ib.

Irritants. of penis, 258

Jaguar, fertility of hybrid with lion, 641
Jelly-fish, form of spermatozoa in, 169
Juniper, abortion caused by, 659

K

Kangaroo, cestrous cycle in, 36

Karyogen, 311

Keratin, composition of, 288 ; in eggs of
lower Vertebrates, 289 sqq. ; in eggs of
herring, 290 ; in eggs of Bombyx, 292

Kidney during senescence, 718

Labia major, 74

Labia minora, 74

Labour, duration of, 568

" Labour pains," 565 ; pressure of, 566

Labyrinth of placenta, 447

Lacertilia, yolk-sac of, 415

Lactalbumen in milk, 594

742

SUBJECT INDEX

Lactation, 33 ; Chapter XIII., passim ;
period of, in walrus, 55 ; effect of, on
cestrous cycle, 69 ; corpus luteum dur-
ing, 149 ; and menstruation, 369, 598,
608 ; effect of pituitary gland on, 383 ;
influence of stage of, on milk, 596 sqq. ;
and ovariotomy, 598, 611, 622; ad-
vance of, 598 sq. ; duration of, 599 sq. ;
duration of, in cow, ib. ; duration of, in
man, 600 ; after paraplegia in man, 609;
foetal hormone, theory of, 611 ; in
relation to placenta, 612 sq. ; and
castration, 614 ; before parturition in
rabbit, 615 ; commencement of, in
Dasyurus, ib. ; commencement of, in
man, ib. ; before parturition in goat,
ib. ; causation of, in Monotremata,
ib. sq. ; as controlled by corpus luteum,
ib. ; explanation of, in virgin dog, 617 ;
corpus luteum as essential to, 621 sq. ;
effect of prolonged, on fertility, 637

Lactic acid in milk, 594

Lactiferous ducts, 588

Lactose, in maternal organism, 537 ; in
urine of puerperium, 540 ; in milk,
594 ; formation of, in guinea-pig, 603 ;
formation of, in goat, 602 sq. ; in
colostrum, 619

Lactosuria, 602 ; during pregnancy, 539 sq.

Lsevulinic acid, 307

Lsevulose, in maternal organism, 537 ;
in foetal rabbit, ib. ; in foetal cow, ib. ;
in foetal sheep, if>.

Lamprey, polyspermy in, 183 ; partheno-
genesis in, 234 ; sex-determination in,
664

Lancelet, see Amphioxus lanceolatus

Land-snail, breeding season in, 13

Lark, mating habits ,of, 25

Larynx, effect of castration on, 321

Lead, effect of, on germ- cells, 209

Lecithin, 310 ; in corpus luteum, 274 sq. ;
in hen's egg, 277, 279 sq., 282 ; in yolk
of egg, 283 ; in spermatozoa, 303 ; in
blood of pregnancy, 542 ; in milk, 594

Lemur, cestrous cycle in, 56 ; uterine
cycle in, 91

Lemuridae, placenta of, 408, 440

Lepidoptera, sex-determination in, 664,
678

Lepidosiren, breeding season in, 16 ;
breeding phenomena in, 26

Lepidosteus, breeding season in, 16

Lepilemur, placenta of, 441

Leptotenic stage of oogenesis, 116, 155

Lepus, formation of corpus luteum in, 145

Lepus cuniculus, see Rabbit

Lepus variabilis, oestrous cycle in, 38

Leucine, 288, 304

Leucocytes, 96 sq., 104 sq.

Leucocytosis, 556 ; during parturition, 572

Life, duration of, 721 sqq. ; phases in,
Chapter XVI.

Life cycle, theory of, 225 ; in Arbacia,
227 ; in Tautogolabrus, ib. ; in Fundulus,

ib. ; in Asterias, ib. ; in frog, ib. sq. ;
in salamander, ib. ; in JUoniezia, 228

Limnea, breeding season in, 13

Linnet, phenomena associated with breed-
ing in, 27 ; in captivity, 629

Linseed, sterility caused by excess of, 631

Lion, oestrous cycle in, 52 ; period of
gestation in, 53 ; fertility of hybrid with
jaguar, 641

Lipase in placenta, 465

Lipochromes, 242 ; of corpus luteum, 273 ;
of Maja squinado, 294 sq.

Lipoids, 310 ; in corpus luteum, 274 ;
in ovary, 274 ; in semen, 297 ; meta-
bolism of, in placenta, 297, 504

Lipolytic ferments, 507

Liquor amnii, function and composition
of, 414

Liquor folliculi, 121 sq.

Litter, factors governing size of, 623 sqq. ;
size of, in Ungulates, 623 ; size of, in
sheep, ib. ; size of, in goat, ib. ; size
of, in pig, ib. ; size of, in Rodentia, ib. sq.;
size of, in rat, 624 ; size of, in Cheirop-
tera, ib. ; size of, in bat, ib. sq. ; size
of, in relation to period of gestation,
ib. ; size of, in relation to number of
teats, ib. ; size of, in man, ib. ; size of,
in rabbit, 625 ; size of, in hare, ib.

Littorina, breeding season in, 12, 14

Liver, hypertrophy of, during pregnancy,
556 ; during senescence, 718

Livetin in egg of fowl, 283. 286

Lobelia, self-sterility of, 215

Lochia, 580 ; rubra, ib. ; serosa, ib. ;
alba, ib. ; amount of, ib. sq.

Loligo, development of, 191

London, sex -ratio in, 687

Longevity, in Actinia mesembryanthemum,
721 ; in Sagartia troglodytes, ib. ; in
Mollusca, ib. ; in Insecta, ib. ; in
Hemiptera, ib. ; in bees, ib. ; in fish,
ib. ; in pike, ib. ; in carp, ib. ; in
Reptilia, ib. ; in crocodiles, ib. ; in
tortoise, ib. ; in birds, ib. ; in canary,
ib. ; in gull, ib. ; in eagle, ib. ; in
heron, ib. ; in owl, ib. ; in raven, ib. ;
in swan, ib. ; in goose, ib. ; in parrot,
ib. ; in Mammalia, ib. ; in elephant,
ib. ; in horse, ib. ; in dog, ib. ; in cat,
ib. ; in rat, ib. ; in mouse, 723 ; in
man, ib. ; in sheep, ib. ; factors control-
ling, 725 sq.

Lota vulgaris, chemistry of spermatozoa
of, 305

Lottia, parthenogenesis in, 234 ; fertilisa-
tion in, 236

Lumbar nerves, 270 ; action of, on genera-
tive organs, 267 ; of rabbit, 560 ; of
cat, ib.

Luteins, 292 ; in corpus luteum, 273 ;
in hen's egg, 281 ; absorption spectrum
of, 274 ; in yolk of egg, 283 ; in Crus-
tacea, 295 sq.

Lutein cysts, 368

SUBJECT INDEX

743

Lycaon pictus, breeding season of, 50 sq. ;
period of gestation in, 51

Lygceus bicrucis, X chromosome in, 673 ;
Y chromosome in, ib. ; synapsis, ib. ;
number of chromosomes in, ib. ; di-
morphism of spermatozoa in, ib.

Lymantria, intersexuality in crosses of
species of, 694

Lyre-bird, phenomena associated with
breeding in, 27

Lysine, 288, 304 sq.

M

Macacus, cestrous cycle in, 57 sq. ; period
of gestation in, 59 ; menstruation in,
89 .on.

Macacus cynomolgus, menstruation in, 58

Macacus fascicularis, menstruation in, 58

Macacus nemestrinus, cestrous cycle in,
58 ; period of gestation in, 59 ; pro-
chorion of, 406 I

Macacus rhesus, 269 ; breeding season in, j
57 sq. ; menstruation in, 58 ; menstrual
cycle in, 84 sqq.

Macacus sinicus, menstruation in, 58

Mackerel, spermatozoa of, 306

Macropus ruflcollis, breeding season in, 36

Macrocytes, 97

Magnesium, in egg of fowl, 278 ; meta-
bolism of, during pregnancy, 519 ; in
foetus of man, 547 ; in pregnancy, 550 ;
in milk, 594 ; in ash of pup, 595 ; in
milk of dog, ib. ; in serum of dog, ib.

Maize, in- breeding in, 217

M aja squinado, vitellorubin in egg of,
294 ; pigment in egg of, ib. ; vitello-
lutein in egg of, ib. ; lipochromes of,
ib. sq.

Malayan hedgehog, cestrous cycle in, 55

Mammae in pregnancy, 559

Mammalia, breeding season in, 24, 365
sq. ; periodicity in breeding in, 29 sq. ;
corpus luteum of, 146 ; fertilisation in,
182; cross-fertilisation in, 211 ; poly-
embryony in, 229 ; prostate gland in,
247 ; respiratory quotient of embryos
of, 286 ; corpus luteum in non-placental,
367 ; sex-determination in, 678 ; her-
maphroditism in, 689 ; longevity in,
722

Mammary and foetal growth, relation
between, 609 sqq.

Mammary gland, 586 ; cycle of, 372 sq. ;
number of, in Centites, 586 ib. ; in man,
ib. ; in guinea-pig, ib. ; in rabbit, ib. ;
position of, in Primates, ib. ; in Cheirop-
tera, ib. ; in Sirenia, ib. ; in elephants,
ib. ; in sloths, ib. ; in Ungulata, ib. sq. ;
in Cetacea, 586 ; of cow, ib. ; of sow,

587 sq. ; of Monotremata, 587 ; of
Echidna, ib. ; of male, ib. ; structure of,

588 sqq. ; pigment of, ib. ; alveoli of,

589 ; theories of secretion of, 591 sqq. ;

normal growth of, 605 sqq. ; growth of,
in rabbit, ib. ; growth of, in horse, 606 ;
growth of, in man, 607 ; during preg-
nancy, in man, 608 ; development of,
during extra-uterine pregnancy, 611 ;
effect of fcetal extract on, ib. sqq. ;
secretion of, in virgins, 614 sq. ; during
pseudo-pregnancy, 616 sq. ; of pseudo-
pregnant rabbit, 617 ; in pseudo-
pregnancy, and in pregnancy, 617 sq. ;
growth of, in latter part of pregnancy,
618 ; before ovulation in rabbit, 619 ;
before ovulation in polycestrous animals,
ib. ; correlation of, with generative
organs in guinea-pig, ib. sq. ; effect
of pituitary gland extract on, 621 ;
effect of placenta extract on, ib.

Mammary growth, factors concerned in,
608 sq.

Mammary secretion, theories of, 591 sqq. ;
factors concerned in, 608 ; after
menopause, 615

Mammary tissue of virgin rabbit, 617

Man, menstruation in, 59 sqq., 358 sqq. ;
oestrus in, 64, 132 ; evidence of
primitive breeding season in, 64 sqq. ;
menstrual cycle in, 74 sqq. ; uterine
mucosa in, 77, 81, 492 ; ova of, 123 sq.,
404, 491, 494, 498 ; number of chromo-
somes in, 126 ; ovulation and menstrua-
tion in, 132 sq. ; discharge of ova into
Fallopian tube in, 135 ; formation of
corpus luteum in, 140 ; degeneration
of corpus luteum in, 147 ; cells of
Sertoli in, 163 ; spermatic! in, ib. ;
spermatozoa of, 168 ; artificial in-
semination in, 176, 647 sq. ; movements
of spermatozoa in, 173 sq. ; length of
vas deferens in, 239 ; uterus masculinus
in, 242 ; composition of ash in, 297 ;
composition of semen in, ib. ; effect
of castration in, 321 n., 323 ; ovario-
tomy in, 340, 347 ; transplantation of
ovaries in, 348 ; ovariotomy during
pregnancy in, 370 ; yolk-sac in, 415,
425 sq. ; " Haftstiel " of, 423, 494, 500 ;
embryo of, 426, 500 ; tubal pregnancy
in, 492 ; placenta of, ib. sqq. ; decidua
serotina of, 493, 502 ; implantation
cavity in, 493 ; blastocyst of, 493,
496, 498; " Gewebspilz !> of, 493;
hypoblast of, ib. ; mesoblast of, ib. ;
trophoblast o'f, 494, 496 sq., 499;
syncytium of, 494 sq. ; uterus of, during
pregnancy, 495 ; " Detrituszone " of,
496 ; implantation cavity of, 497 ;
decidua of, 497, 499 ; compacta of, 498
sq. ; spongiosa of, 498 ; " Eikammer " of,
499 ; glands during pregnancy in, ib. ;
"Zellsiiulen" of, 500; " Haftzotten "
of, 501 ; syncytium of, 502 ; symplasma
of, ib. ; " Fibrinstreifen " of, ib. ;
decidual cells of, ib. ; uterine glands of,
ib. ; glycogen metabolism in placenta
of, 503 ; fat metabolism in placenta of,

744

SUBJECT INDEX

ib. sq. ; lipoid metabolism of placenta
of, ib. ; foetal respiration in, ib. sq. ;
iron metabolism in placenta of, 505
sq. ; albumen metabolism in placenta
of, 506 ; creatin metabolism in placenta
of, ib. ; ferments in placenta of, 507 sq.;
proteolytic enzyme in placenta of, 528 ;
nitrogen retention in, 530 sqq. ; albu-
minuria of pregnancy in, 536 ; glycogen,
storage of, in, 537 sq. ; excretion of
carbohydrates during pregnancy in, 539
sq. ; fat required by fetus of, 542 sq. :
phosphorus in foetus of, 547 ; chemistry
of foetus of, ib. ; energy metabolism
in pregnancy in, 554 ; pituitary during
pregnancy in, 559 ; parturition in, 565 ;
paraplegia and labour in, 571 sq. ;
mechanism of parturition in, ib. ;
prolonged gestation in, 578 ; puer-
perium in, 579 sqq. ; number of mam-
mary glands in, 586 ; teat of, 587 ;
nipple of, 588 ; structure of mammary
gland in, 589 sqq. ; milk of, 594 ;
duration of lactation in, 600 ; nursing
period in, ib. • hyperlactation in, ib. ;
growth of mammary gland in, 607 ;
mammary gland during pregnancy in,
608 ; lactation after paraplegia in, 609 ;
pygopagous twins in, 610 ; commence-
ment of lactation in, 615 ; galactogogue I
effect of corpus luteum extract in, 621 ; |
size of litters in, 624 ; fertility in, 626,
668 sqq. ; sterility in, 632, 646 ; j
number of oocytes in ovary of, 636 ;
impotence in, 638 ; inheritance of
fertility in, 643 ; causes of abortion in,
652 sq. ; birth-rate, 658 sqq. ; sex-ratio
in, 662 ; sex-determination in, 668 ;
sex of " double monsters " in, 679 ;
growth in, 701 sq., 709 sqq. ; growth of
secondary sexual characteristics in, 713 ;
puberty and growth in, ib. ; %)uberty in,
714 ; senescence in, 718 sqq. ; long-
evity in, 723

Manis, placenta of, 409, 442
Markhor, oestrous cycle in, 43 sq.
Marmot, uterine cycle in, 100
Marriage, 29

Marsupial cat, prooestrum in, 106 ; pseudo-
pregnancy in, 106 sq., 576 ; formation
of corpus luteum in, 142 sq. See also
Dasyurus viverrinus

Marsupialia, cestrous xiycle in, 35 sq. ;
period of gestation in, ib. • discharge
of ova into Fallopian tube in, 135;
prochorion of, 405 ; yolk-sac of, 416 ;
mesoblast of, ib. ; teat of, 587
Marsupium of Siphostoma floridce, 690
Masculinisation of guinea-pig, 696
Maternal organism, changes in, during
pregnancy, Chapter XL, passim ; lactose
in, 537 ; laevulose in, ib. ; absorption of
carbohydrate by, ib. ; carbohydrate of,
ib. sq. i fat, absorption of, by, 541 ; fat
of, ib. sq. ; hypercholesterinsemia, 542

Maternal tissues, changes in, during preg-
nancy, 556 sqq.

Maturation, chromosomes in, 125 sq. ;
of spermatozoa, 126, 159, 165 ; of ova,
127, 120 sqq., 125, 127 sqq., 165

Mediastinum testis, 159

Megalokaryocytes of beaver, 475

Meissner's corpuscles, 254

Me.les toxus, see Badger

Membrana granulosa, 121

Membrane formation, 314, 317 : in ova,
182

Mendelism, 199 sqq. ; in pea, 199 sq. ;
in fowl, 200 ; and sex, 201 ; in sheep,
203 sq.

Menidia, chromosomes in, 206

Meningitis during pregnancy, 559

Menopause, 64, 714 sqq. • mammary
secretion after, 615 ; in male, 714 ;
palpitation in, 715 ; dyspepsia in, ib. ;
sweating in, ib. ; hysteria in, i&. ;
pyometra in, ib. ; stages in, 715 sqq. ;
in domestic animals, 717 ; in horse, ib. ;
in sheep, ib. ; in cat, ib. ; in white
mouse, ib. ; in white rat, ib.

Menorrhagia, definition of, 61

Menstrual cycle, in man, 74 sqq. ; stage
of quiescence of, ib. ; constructive
stage of, 75 sqq. ; destructive stage of,
78 sqq. ; stage of repair of, 82 sqq. ;
in monkeys, 84 sqq. ; resting stage of,
85 ; growth of stroma, ib. ; increase
of vessels, ib. ; breaking down of
vessels, 85 sq. ; formation of lacunae,
86 ; rupture of lacunae, 86 sq. ; forma-
tion of menstrual clot, 87 ; recuperation
stage of, 88 ; in Cercocebus, 90 sq.

Menstrual fluid, composition of, 82

Menstruation, 33, 57 sqq., 78 sqq., 85 sq.,
377, 574 ; effect of climate on, 60 n. ;
in Macacus fascicularis, 58 ; in Macacus
cynomolgus, ib. ; in Macacus sinicus,
ib. ; in Papio porcarius, ib. ; in man,
59 sqq., 132, 356 ; excretion of calcium
during, 63 ; blood pressure during,
ib. ; coagulation of blood during, ib. ;
pulse-rate during, ib. ; nitrogen meta-
bolism during, ib. ; during lactation,
69, 362, 598, 608 ; in Macacus, 89 sq. ;
and ovulation, 132, 362 n. ; pathological
character of, 158 ; in Tarsius spectrum,
132 ; in monkeys, 132 ; in Primates,
156 sqq. ; significance of, 156 sq. ;
factors determining, 358 sqq. • nervous
reflexes and, 358 sq. ; absence of, after
ovariotomy, 360 sq. ; after ovarian
transplantation, ib. ; and lactation, 362 ;
influence of, on milk, 596

Merino sheep, oestrous cycle in. 41 ;
period of gestation in, 68 n. ; Mendelism
in, 203

Meriones longifrons, oestrous cycle in, 37 ;
prolonged gestation in, 578

Meriones shawi, oestrous cycle in, 37 sq. ;
prolonged gestation in, 578

SUBJECT INDEX

745

Mesoblast, 411 ; origin of, 412 ; of
Marsupialia, '416; Carnivora, 420;
of mouse, 421 ; of rat, ib. ; of rabbit,
ib. sq. ; of man, 493

Mesoderm, 406

Mesometrium of mole, 484

Metabolism, influence of reproductive
organs on, 388 sqq. ; effects of castration
on, ib. ; of phosphorus, 389 ; of calcium,
ib. ; of protein, ib. ; gaseous, 390 ; of
nitrogen, 391 ; of iron in placenta,

457 sq., 505 sq. ; of fat in placenta,

458 sqq., 471 sq., 475, 503 sq. ; of glyco- I
gen in placenta, 460 sqq., 471, 475, !
503 ; of glucose, 463 ; of protein in j
placenta, 464 ; in placenta, 466 ; of
lipoids in placenta, 504 ; of albumen
in placenta, 506 ; of creatin in
placenta, ib. ; of creatinine in placenta,
ib. ; effect of placenta on, 515 ; changes j
in, during pregnancy, 518 ; energy of,
during pregnancy, 519 ; during preg-
nancy in dog, 524 sq. ; of metals during
pregnancy, 547 sqq. ; of salts during
pregnancy, 547 sqq. ; summary of, of
pregnancy, 555 ; of tumour-bearing
animals compared with that of pregnant
animals, ib.

Metals, metabolism of, during pregnancy,
547 sqq.

Metoestrum, 33

Micropyle of ovum, 132

Microsporon furfur, 559

Migration of birds, 22 sq.

Milk, composition of, 594 sq. ; properties
of, 594 sq. ; protein in, 594 ; size of
globules in, ib. ; water in, ib. ; fats
in, 594, 604 ; of man, 594 ; of cow, ib. ;
carbohydrates in, ib. ; salts in, ib. ;
caseinogen in, ib. ; lactalbumen in, ib. ;
lactoglobulin in, ib. ; whey albumen in,
ib. ; casein in, ib. ; olein in, ib. • palmatin
in, ib. ; stearin in, ib. ; butyrin in, ib. ;
capronin in, ib. ; lecithin in, ib. ;
cholesterin in, ib. ; lactose in, ib. ;
milk-sugar in, ib. ; animal gum in, ib. ;
dextrin in, ib. ; lactic acid in, ib. ; cal-
cium in, ib. ; potassium in, ib. ; mag-
nesium in, ib. ; sodium in, ib. ; iron
in, ib. ; of dogs, 595 ; oxygen in, ib. ;
nitrogen in, ib. ; carbon dioxide in, ;
ib. ; of cow and man compared, ib. ; :
compared with colostrum, ib. ; composi-
tion of ash of, in dog, ib. ; influence
of diet on composition and yield of,
596 sqq. ; influence of breed on, ib. ;
influence of stage of lactation on, ib. ;
influence of season on, ib. ; influence
of milking time on, ib. ; influence •
of sexual excitement on, ib. ; influ-
ence of climate on, ib. ; influence of
weather on, ib. ; influence of menstrua-
tion on, 598 ; influence of ovariotomy
on, ib. ; discharge of, 600 sq. ; organic
constituents of, 601 sqq. ; formation of

24 A

caseinogen in, 601 ; formation of fat in,
ib. sq. ; formation of sugar in, 602 sqq. ;
effect of phloridzin on, 604 sq. ; effect
of pituitary extract on, ib. sq. ; the
nitrogen-lactose ratio in, 605
Milk cisterns of udder, 586
Millions fish, see Girardiwits pceciloides
Miridse, uterine cycle in, 100
Mitoses, 125 sq.
Mittelschmerz, 59 n.

Molasses, sterility caused by excess of, 631
Mole, development of male generative
organs in, 55 ; breeding season in, ib. ;
interstitial cells in ovary of, 120 n. ;
vesicula seminalis of, 243 ; prochorion
of, 406; fate of placenta of, 409;
yolk-sac in, 424 ; placenta of, 434 ;
mesometrium of, ib. ; blastocyst of,
ib. • trophocyst of, ib. sq. ; cytoblast
of, 484 ; plasmodiblast, ib. ; fetal
atrophy in, 656

Mollusca, breeding season in, 12 sqq. ;
hermaphroditism in, 688 ; longevity in,
721

Moniezia, life cycle in, 228
Monkey, menstrual process in, 57 sq. ;
oestrous cycle in, 57 sqq. ; menstrual
cycle in, 84 sqq. ; ovulation and
menstruation in, 132 ; form of sperma-
tozoa in, 169 ; " Haftstiel " of, 423 ;
yolk-sac in, 425 ; puerperium in, 584 ;
fertility in, 629
Moncestrous animals, corpus luteum in,

373

Monoestrum, 34, 66

Monotremata, 415 ; osstrous cycle in, 35 ;
discharge of ova into Fallopian tube in,
135 ; mammary glands of, 587 ;
causation of lactation in, 615 sq.
Mons veneris, 74
Moor hen, reversal of matins: instinct in,

690

" Morning sickness," cause of, 545
Mosquito, egg-formation in, 12
Moufflon, see Ovis musimon
Mouse, oastrous cycle in, 37 ; maturation
of ova in, 127 ; ovulation in, 130 ;
formation of corpus luteum in, 138 sqq. ;
retention of ovum in follicle of, 151 ;
artificial insemination in, 176, 649 ;
in-breeding in, 217 ; mesoblast of, 421 ;
yolk-sac in, 422 sq. ; trophoblast of,
422 ; placenta of, 451 ; vital staining
in, 466 ; placenta of, 467 sq. ; move-
ments of fertilised ovum of, 467 ; sym-
plasma in, ib. ; ectoplacental cone of,
ib. ; " Eikammer " of, 467, 470 ;
inversion of germinal layers in, 468 ;
implantation cavity of, ib. sqq. ;
decidual cavity of, 468 sq. ; serotina
of, 469 ; giant cells of, 469 sq. ; allan-
tois of, 470 ; glycogeii metabolism in,
471 ; fat metabolism, ib. sq. ; placen-
tal haemopoiesis, 518 ; prolonged gesta-
tion in, 578 ; inheritance of fertility

746

SUBJECT INDEX

in, 643 ; foetal atrophy in, 656 sq. ;

sex-determination in, 669 ; growth of,

712 ; puberty in, 714 ; menopause in,

717 ; longevity in, 723
Mucin, in embryo, 287, 463 ; in "egg-
membrane, 290
Mucinogen, 290
Mule, sterility of, 211
Murinus, amnion of, 490 n.
Mus, formation of corpus luteum in, 145
AIv-s decumanus, see Rat
Mus minutus, cestrous cycle in, 37
Mus musculus, see Mouse
Mus rattus, breeding season in, 37 ;

period of gestation in, ib.
Mus sylvaticus, cestrous cycle in, 37
Musca corvina, pcecilogonie in, 228
Muscle during senescence, 718
Musk deer, perineal gland in, 253 ;

inguinal gland in, ib. ; preputial gland

in, ib. ;

Musk-ox, cestrous cycle in, 45
Musk rat, perineal gland in, 253 ; inguinal

gland in, ib. ; preputial gland in, ib.
Mussel, see Mytilus
Mustelus Icevis, 415 ; egg-membrane in,

289
Myliobatis, formation of corpus luteum in,

145

Myometrial gland, 372, 577, 618
Myriapoda, sex-determination in, 678
Myrmecophaga, placenta of, 442
Mytilus, hybridisation of, 213

N

Nahrzellen, 417
Necrobiosis, 592
Nematode, maturation of ova in, 128 ;

sex-determination in, 678
Nematus ventricosus, sex-determination

in, 665 sq.

Nemertea, breeding season in, 9
Nephritis of pregnancy, 552
Nereis, sperm -agglutination in, 186 ;

fertilisation in, 194 sq. ; development

of, 227

Nereis dumcrilic, breeding season in, 10 n.
Nereis limbata, breeding season in, 10 n.
Nervi erigentes, 267, 272, 564
Neuronophags, 726
Newt, sexual activity in, 21 ; artificial

impregnation in, 176 ; ferment of

gonad in, 318
Nipple of man, 588
Nitrogen, retention of, during pregnancy,

530 sqq., 555 ; excretion of, 532 sqq. ;

in milk, 595
Nitrogen balance, during pregnancy,

525 sq. ; during pregnancy, in dog,

526 sqq. ; during pregnancy, in rabbit,
ib.

Nitrogen-lactose ratio in milk, 605

Nitrogen metabolism, 391 ; in bitch, 49 ;
during menstruation, 63 ; during preg-
nancy, 519

Non-deciduata, classification of, 408

Nucleic acid, 309, 311 ; from spermato-
zoa, 307

Nucleolus, 109

Nucleo protein, 281 sq. ; in head of sper-
matozoa, 312 ; in fcetus, 548

Nucleotide, 309

Nucleus, 109 ; ratio of, to cytoplasm,
702 sq.

Nursing period, 599 ; in man, 600

Nutrition, of fcetus in Perameles, 36 n. ;
placenta as an organ of, Chapter X. ;
influence of, on fertility, 627 sqq. ;
influence of, on sex-determination,
669 sqq., 684 sqq.

Nycticebus, placenta of, 440

Nylghau, cestrous cycle in, 45

Ob-placental folds of rabbit, 452

Ocneria dispar, effect of castration in,
325

Odontosyllis euopla, breeding season in,
10 n.

(Edema in pregnancy, 552

(Estrous cycle, in Mammalia, Chapter II.,
passim ; in Monotremata, 35 ; in
platypus, ib. ; in Echidna, ib. ; in
Marsupialia, ib. sq. ; in Pharcolarctus
cinereus, ib. ; in kangaroos, 36 ; in
Marsupial cat, ib. ; in Dasyurus
viverrinus, ib. ; in opossum, ib. ; in
Didelphys aurita, ib. ; in Rodentia,
37 sqq. ; in Mus decumanus, 37 ; in
Mus musculus, ib. ; in Mus minutus,
ib. ; in Mus sylvaticus, ib. ; in Arvicola
glareolus, ib. ; in Arvicola agrestis, ib. ;
in Eliomys quercinus, ib. ; in Gerbillus
hertipes, ib. ; in Dipodillus campestris,
ib. ; in Dipodillus simoni, ib. sq. ; in
Meriones shawi, ib. ; in Meriones longi-
frons, ib. ; in Lepus cuniculus, 38 ;
in Lepus variabilis, ib. ; in Sciurus
vulgaris, ib. ; in Pachyuromus duprasi,
ib. ; in Cavia porcellus, ib. ; in Ungulata,
39 sqq. ; in sheep, 39, 42 sq. ; in
Ovis species, 39 ; in Merino sheep,
41 ; in goat, 43 ; in cattle, ib. ; in
ibex, ib. sq. ; in markhor, ib. ; in
barasingha, ib. ; in Hemitragus, ib. ;
in bison, ib. sqq. ; in deer, 43 sq. ;
in fallow-deer, 44 ; in gnu, 45 ; in
Gazella dorcas, ib. ; in giraffe, ib. ;
in eland, ib. ; in nylghau, ib. ; in water-
buck, ib. ; in gayal, ib. ; in axis, ib. ;
in wapiti deer, ib. ; in red-deer, ib. ;
in camel, ib. ; in walrus, ib. ; in yak,
ib. ; in musk-ox, ib. ; in pig, 46 ; in
hippopotamus, ib. ; in Timor pony, ib. ;
in horse, ib. sq. ; in elephant, 47 ; in

SUBJECT INDEX

747

Cetacea, ib. sq. ; in porpoise, 48 ; in
dog, ib. aqq. ; in carnivora, ib. ; in
wolf, 50 ; in cat, 51 ; in wild cat, 52 ;
in lion, ib. ; in puma, 53 ; in bear,
ib. ; in ferret, ib. ; in polecat, ib. ;
in stoat, ib. sqq. ; in weasel, ib. ; in
pine martin, ib. sq. ; in otter, 54 ; in
harp seal, ib. ; in seal, ib. ; in fur seal,
ib. ; in walrus, ib. ; in badger, ib. n. ;
in Insectivora, 55 sq. ; in shrew, 55 ;
in water-shrew, ib. ; in Malayan hedge- .
hog, ib. ; in mole, ib. ; in bat, 56 ;
in Primates, ib. sqq. ; in lemurs, 56 ; in
Tarsius spectrum, ib. ; in monkey,
57 sqq. ; in Macacus, 57 sq. ; in Cerco-
cebus, 58 ; in Papio, ib. ; in Macacus
nemestrinus, ib. ; in Cercopithecus, ib. ;
changes in uterus during, Chapter III.,
passim ; in guinea-pig, 134 n.
(Estrum, see (Estrus

(Estrus, 32 ; definition of, 33 ; effect of
lactation on, 69 ; effect of, on Bartho-
lin's glands, 51 ; in Carnivora, 92 ;
in man, 132 ; in ferret, 364

Oleic acid in yolk of egg, 283

Olein in milk, 594

Omphaloidean placenta, 424

Omphaloidean region in hedgehog, 480

Omphaloidean syncytium of shrew, 482

Oncidium, self-sterility of, 215

Oocytes, number of, in human ovary, 636 ;
number of, in ovary of rat, ib.

Oogenesis, 109, 115 sqq., 155, 165; in rabbit,
115; protobroque cells in, 116 ; deuto-
broque cells in, 116, 118; leptotenic
stage in, 116, 155 ; synaptenic stage in,
116 sq., 155 ; pachytenic stage in, 117,
155; diplotenic stage in, 117, 155;
dictyate stage in, 117, 155

Oogonia, 115

Oophorine, 355

Oosperm, see Zygote

Ophelia, parthenogenesis in, 284

Ophryotricha puerilis, intersexuality in,
692

Opossum, breeding season in, 36 ; cestrous
cycle in, ib. ; polyembrony in, 229 ;
yolk-sac in, 415 ; embryo of, 417 ;
period. of gestation of, ib. sq.

Orca, placenta of, 442

Oreas, placenta of, 432

Organ of Giraldes, 71

Organ of Rosenmiiller, 7 1

Organ of Weber, 241

Orgasm, 264

Oriole in captivity, 629

Ornithin, 304

Ornithodelphia, 415 ; see Monotremata

Orycteropus, placenta of, 409, 442

Os penis in Carnivora and Rodentia, 256

Osteomalacia, cause of, 298 ; effect of
ovariotomy on, 389 ; in puerperium,
549

Ostrich, ovariotomy in, 344 ; fertility in,
630

Otter, cestrous cycle in, 54 ; placenta of,

448

Ovalbumen in white of egg, 287
Ovarian extract, 391 ; causing heat, 362
Ovarian ovum, 404
Ovarian pregnancy, 137
Ovarian transplantation, 360 sq.
Ovarine, 355

Ovariotomy, in deer, 340 ; in man, 340,
347 ; in fowl, 341 sqq. ; in Aves, ib. ;
in duck, 343 sqq. ; in ostrich, 344 ;
in rat, 346 ; in cow, ib. ; in rabbit,
347 sqq. ; in guinea-pig, ib. ; in
relation to menstruation, 360 sq. ; in
dog, 361 ; in sow, ib. ; and abortion,
366 ; during pregnancy in dog, 369 ;
during pregnancy in man, 370 ; during
pregnancy in pig, ib. ; during pregnancy
in rat, ib. ; during pregnancy in rabbit,
371 ; effect of, on uterine mucoga, 376 ;
effect of, on pituitary gland, 382 ; in
regard to colloid production, 385 ;
effect of, 387 ; in pig, 388 sq. ; effect
of, on osteomalacia, 389 ; effects of, in
dog, 391 ; influence of, on milk, 596 ;
and lactation, 598, 611, 622 ; effects of,
in fowl, 699

Ovary, 70 sq., Chapter IV., passim ;
of cat, 109 ; development of, ib. sqq. ;
of dog, 1 10 ; structure of, ib. sq. ;
of rabbit, 111; of pig embryo, 112;
interstitial cells of, 142 n., 145, 147 ;
number of ova in, 155 ; lipoids in, 274 ;
cholesterin in, ib. sq. ; fat in, 275 ;
source of ichthulin in, 292 ; source of
phosphorised fats in, ib. ; as organ of
internal secretion, Chapter IX., passim ;
correlation between female characters
and, 340 ; transplantation of, in fowl, .
343 ; transplantation of, in guinea-pig,
346 ; interstitial cells of, 346, 386 n. ;
effect of Rontgen rays on human, 347 ;
in rabbit, 348 ; heteroplastic graft of,
350 sqq. ; homoplastic graft of, 351 sqq. :
compensating hypertrophy of, 357 sq. ;
interstitial cells of, during gestation,
376 ; effect of hysterectomy on, 377 ;
general conclusions regarding internal
secretion of, 386 sqq. • hormones of, 577 ;
transplantation of, in guinea-pig, 620 ;
number of oocytes in human, 636 ;
number of oocytes in, of rat, ib. ; at
puberty, 713

Oviduct, see Fallopian tube
Ovigenine, 355
Oviposition, in fire-bellied toad, 136 ;

in fetid toad, ib. ; in toad, ib.
Ovis, formation of corpus luteum in, 145
Ovis ammon, cestrous cycle in, 39
Ovis argali, cestrous cycle in, 39
Ovis burrhel, cestrous cycle in, 39
Ovis canadensis, oastrous cycle in, 39
Ovis musimon, cestrous cycle in, 39
Ovis poli, cestrous cycle in, 39
Ovis tragelaphu*, cestrous cycle in, 39

SUBJECT INDEX

Ovis vignei, CEstrous cycle in, 39 sq.

Ovomucoid in white of egg, 287

Ovulation, 120 sqq., 156 ; in rabbit, 129 ;
in mouse, 130 ; in rat, ib. ; in guinea-
pig, ib. ; in pig, ib. ; in ferret, 130, 134 ;
in cat, 131 ; in horse, ib. ; in donkey,
ib. ; in cattle, ib. ; in sheep, ib. ; in
bat, ib. sq. ; in Primates, 132 ; in
relation to menstruation, 132, 362 n.; in
Parsius spectrum, ib. ; in monkey, ib. ;
in man, ib. sq. ; in fowl, 134 n. ; in
pigeon, 135 ; mammary glands before,
in rabbit, 619 ; mammary glands before,
in polyoestrous animals, ib.

Ova, struggle among, in Coelenterates,
120 n. ; maturation of, 120 sqq., 125 ;
production of multiple, 121 n. sq. ;
human, 123 sq. ; maturation of, 125
sqq. ; fertilisation of, 134 sq. ; retention
of, in follicle, 151 ; number of, in ovary,
155 ; maturation of, 165 ; membrane
of, 182 ; micropyle of, 182 ; oxidation
process in, 185 sqq. ; transplantation of,
209 ; in- breeding and vitality of, 219
sq. ; chemistry of, 276 sqq. ; source of
iron in, 292 ; chemistry of Invertebrate,
292 sqq. ; of sheep, 404 ; of man, ib. ;
albumen layer of, in rabbit, 406 ;
zonary villi of, 445 ; carbohydrate in,
463 ; glucosamine in, 463 ; movements
of, after fertilisation in mouse, 467 ;
of hedgehog, 478 ; sex-determination
by maturity of, 669 ; dimorphism of,
in Talceporia tubulosa, 672 ; dimor-
phism of, in Raja batis, 679 ; di-
morphism of, in Hydatina senta, ib. ;
dimorphism of, in Phylloxera, ib. ; di-
morphism of, in Dinophilus apatris, ib.

Owl, longevity in, 722

Oxidase ferments, 507

Oxidation, 313 sqq. ; in ova, 185 sqq. ;
at fertilisation, 186 sqq. ; in ovum of
Stronglocentrotus, 188, 191 ; in ovum
of Echinus microtuberculatus, 192 ; in
ovum of Glutathione, 197 ; in ovum
of Echinus miliaris, ib. ; of fat, 284 ;
in parthenogenesis, 285 ; ferments of,
507

Oxygen, absorption of, by foetus, 464 sq. ;
consumption of, during pregnancy in
rat, 553 ; in milk, 595

Pachytenic stage of oogenesis, 117, 155
Pachyuromus duprasi, oestrous cycle in,

38

Pacinian body, 75

Pacinian corpuscles of penis, 254, 257
Paecilogonie, 228 ; in Musca corvina,

228 n.

Psedogenesis, 228 ; in Chironomus, 228 n.
Pain-spots of penis, 254 sq.
Palmatin in, milk, 594

Palmitic acid in yolk of egg, 283

Palolo-worm, breeding season in, 9 sq. ;
maturation of ova in, 128 sq. ; polar
body in, 129

Palpitation in menopause, 715

Paludina, spermatozoa in, 168, 672 ;
ova in, 672

Papio, oestrous cycle in, 58

Papio porcarius, menstruation in, 58

Paramcecium, 384 ; rejuvenescence in,
221 sq. ; assertive mating in, 221 ;
endomixis in, 223

Paramcecium aurelia, rate of fission in, 6

Paraplegia during pregnancy, 514 ; in
man, 571 sq. ; and lactation, 609

Parasitic castration, in hermit crab, 326 ;
in spider crabs, ib.

Parathyroid, 385

Paroophoron, 71

Parovarium, 71

Parrot, in captivity, 630 ; longevity in,
722

Parthenogenesis, 126 n. ; artificial, 185,
194, 230 sqq., 313; natural, 230; in
Aphaedi, ib. ; in Bombyx mori, ib. ; in
Echinodermata, ib. sq. ; in Chatop-
terus, 230, 233 ; in Arbacia, 231 sq.,
314, 317; in Asterias forbesii, 231 sq. ;
in Strongylocentrotus • purpuratus, 232 ;
in Ophlia, 234 ; in Acmcea, ib. ; in
Lottia, ib. ; in lamprey, ib. ; in frog,
234, 316; and the chromosome num-
ber, 238 ; oxygen absorption during,
285 ; in plant-lice, 669 ; in Daphnia,
670 ; in Simocephalus, ib. ; in Hyda-
tina senta, ib.

Parturition, Chapter XII. ; in man, 565 ;
in horse, ib. sq. ; stages of, 566 sqq. ;
in Ruminants, 569 ; in sheep, ib. ;
in pig, ib. ; in dog, ib. ; in cat, ib. ;
in Carnivora, ib. ; in rat, ib. sq. ; in
opossum, 570 ; in Dasyurus, ib. ; in
Perameles, ib. ; in kangaroo, ib. ; nervous
mechanism of, ib. sqq. ; mechanism of, in
cat, 571 ; mechanism of, in rabbit, ib. ;
mechanism of, in dog, ib. ; mechanism
of, in man, ib. sq. ; leucocytosis during,
572 ; changes in maternal organism
during, ib. ; "after pains" of, 579;
area of placenta after, 582

Patella, breeding season in, 12 ; fertilisa-
tion in, 229

Pea, Mendelism in, 199

Pea-fowl, fertility in, 628

Pelican, phenomena associated with breed-
ing in, 27

Pelodytes, hybridisation in, 210

Peltogaster, 691 ; effect of, on crab, 326

Penis, 253 sqq. ; relation of scrotum to,
165 ; function of, 253 ; structure of,
ib. sqq. ; end-bulbs of, 254 ; Pacinian
corpuscles of, 254, 257 ; prepuce ef,
254; glans of, 254, 260; heat-spots
of, 254 ; pain-spots of, 254, 255 ;
cold-spots of, ib. ; arteries of, 255, 257 ;

SUBJECT INDEX

749

helicine arteries of, 255 ; erectile tissue
of, 256 sq. ; sexual irritants of, 258 ; of
sheep, 259 ; filiform process of, ib.
sqq. ; of giraffe, 259 ; of gazelle, ib. ;
fibre-cartilage bodies of, ib. ; of bull,
261 ; blood pressure in, 262 ; erection
of, ib. sqq. ; retraction of, ib.

Penguin, periodicity of breeding in, 29

Pentoses, 282

Perameles, foetal nutrition in, 36 n. ;
corpus luteum in, 367 ; placental
structure of, 418 sq. ; foetal membranes
of, 419 ; period of gestation in, ib.

Percaglobulin in eggs of perch, 291

Perch, egg-membrane in, 290 ; perca-
globulin in eggs of, 291

Perineal gland, 253 ; in musk deer, ib. ;
in musk rat, ib. ; in hamster, ib.

Periodicity in breeding, 10, 13, 28 sqq. ;
in salmon, 29 ; in Mammalia, ib. sq. ;
in penguin, 29 ; in whale, ib. ; in
elephant, ib. ; in deer, 30

Period of gestation, see Gestation

Peripatus, breeding season in, 10

Peri-placental folds of rabbit, 452

Peristalsis of uterus, 173 sq.

Peritoneum, 164 n. ; connection of, with
uterus, 71

Peri vascular sheath, 454

Permanent placenta of Tupaia javanica,
486

Persistent corpora lutea, 373

Petrel, incubation period in, 23

Phagocytosis in bat, 488

Phalarope, phenomena associated with
breeding in, 27

Phascolarctus, breeding habit in, 67

Phascolarctiis cinereus, oestrous cycle in,
35

Phascolomys, breeding habit of, 67

Pheasant, hermaphroditism in, 694

Phloridzin, effect of, on milk, 604 sq.

Phorphatides in corpus luteum, 274 sq.

Phosphoprotein, 290

Phosphorised fats, 310 ; in egg of fowl,
279 sqq. ; in eggs of herrings, 290 ;
source of, in ovary, 292 ; in eggs of
insects, 293 ; in spermatozoa, 302 ;
in tails of spermatozoa, 311

Phosphorus, 307 ; in egg of fowl, 278 sq.,
282 ; metabolism of, 297, 389 ; meta-
bolism of, during pregnancy, 519, 550 ;
in foetus of man, 547 ; in pregnancy,
550 sq. ; in urine, 551 ; in ash of pup,
595 ; in milk of dog, ib. ; in serum of
dog, ib. ; as cure for impotence, 638

Phylloxera, dimorphism of ova in, 679 ;
sex-determination in, 674 n.

Pig, cestrous cycle in, 46 ; period of
gestation in, 46, 68 n. ; uterine cycle in,
103, 106; ovary of embryo of, 112;
ovulation in, 130 ; formation of corpus
luteum in, 144 ; form of spermatozoa
in, 169 ; in- breeding in, 216 ; ovario-
tomy in. 361, 388 sq. ; ovariotomy

during pregnancy in, 370 ; prochorion
of, 406 ; yolk-sac in, 420 ; chorion
of, 427 ; blastocysts of, ib. sq. ; pla-
centa of, 427 sqq., 509 ; trophoblast of,
428 ; uterine mucosa of, ib. ; source
of fcetal iron, 434 ; mammary glands of,
587 sq. ; size of litters in, 623 ; fertility
in, 627 sq., 636 ; inheritance of fertility
in, 643 ; fcetal atrophy in, 656 ; di-
morphism of spermatozoa in, 678 n. ;
hermaphroditism in, 695 ; growth of,
707 ; puberty in, 714

Pigeon, maturation of ova in, 128 ; polar
body in, 128 ; fertilisation in, 134 sq. ;
ovulation in, 135 ; fertility in, 628 ;
sex-determination in, 685 sq. ; inter-
sexuality in, 686, 694. See also Ring-
dove

Pigment, 434 ; of uterine mucosa, 97 ; of
mammary glands, 588 sqq.

Pike, longevity in, 722

Pineal gland, effect of, on generative
organs, 384 ; effect of extract of, on
tadpoles, 384

Pine martin, oestrous cycle in, 53 sq.

Pisces, see Fish

Pituitary gland, effect of castration on,
381 sq. ; effect of ovariotomy on, 382 ;
during pregnancy, ib. ; effect of, on
lactation, 383 ; extract of, 383, 604
sq., 621 ; during pregnancy in man,
559

Pityriasis versicolor, 559

Placenta, Chapter X., passim ; historical,
393 sqq. ; as organ of foetal respira-
tion, 394 ; intervillous spaces of, 395 ;
of Garni vora, 408, 410, 442 sqq. ; of
Proboscidea, 408, 450 ; of Rodentia,
408, 451 ; of Insectivora, 408, 410,
476 sqq., 509 ; of Cheiroptera, 408,
410, 487 sqq. ; of Lemuridae, 408 ; of
Simiida3, 408 ; of Ungulata, 408, 410 ;
of Primates, 408, 410, 490 sqq., 509;
of Cetacea, 408, 410; of Sirenia, 408
sqq. ; of Edentata, 409 sq. ; of Manis,
409 ; of Bradypus, ib. ; of Orycteropus,
ib. ; of dugong, ib. ; fate of, in mole,
ib. ; of hedgehog, 409, 476 sqq. ; of
shrew, 409, 481 sqq. ; of Gymnura, 409 ;
of Tupaice, 409, 485 ; of Galeopitheci,
409 ; of Indeciduata, 427 sqq. ; of
Ungulata, 427 sqq., 509 ; of pig,

427 sqq., 509 ; of Galago agisymbanus,
428, 440 ; of horse, 428 sq. ; of sheep,

428 sqq., 449, 509 ; of cow, 429, 432
sq., 435 ; of Cervus, 432 ; of giraffe,
ib. ; of Oreas, ib. ; of Tetraceros, ib. ;
of sheep, 435 ; of Lemuroidea, 440 ;
of Tarsius, ib. ; of NycticebuA, ib. ; of
Lepilemur, 441 ; of Cetacea, 442 ; of
Orca, ib. ; of Sirenia, ib. ; of Halicore,
ib. ; of Edentata, ib. ; of Orycteropus,
ib. ; of Myrmecophaga, ib. ; of Taman-
dua, ib. ; of Bradypus, ib. ; of Dasypus,
ib. ; of Manis, ib. ; of Choice-pus, ib. ;

750

SUBJECT INDEX

of Deciduata, ib. sqq. ; zonary, 442 ;
of ferret, 443 ; of dog, 444 sqq. ; of
cat, ib. ; "green border" of, 447;
" green pockets " of, ib. ; of otter,
448 ; of badger, ib. ; of Hyrax, 450 sq. ;
of rabbit, 451 sqq., 457 ; of mouse,
451, 467 sqq. ; of rat, ib. ; of guinea-
pig, 451, 472 sq. ; iron metabolism
in, 457 sq., 505 sq. ; fat metabolism
in, 458 sqq., 471 sq., 475, 503 sq. ;
iron granules in, 459 ; glycogen in,
of rabbit, 460 ; glycogen metabolism
in, 460 sqq., 471, 475, 503; distal
glycogen in, 461 sq. ; proximal glyco-
gen in, ib. ; protein in, of rabbit, 464 ;
protein metabolism in, ib. ; respiration
in, 464 sq., 504 sq. ; ferment content
of, 465 sq., 507 sq., 516 sq. ; vital
staining of, 465 sq. ; amylase in, 465 ;
lipase in, ib. ; crepsin in, ib. ; meta-
bolism in, 466 ; of beaver, 475 sq. ;
of shrew, 481 sqq. ; of mole, 484; of
Centetes ecaudatus, 486 sq. ; of bat, 487
sqq. ; of Pteropus edulis, 489 sq. ; of
Semnopithecus nasicus, 491 '; of man,
492 sqq. ; lipoid metabolism in, 504 ;
albumen metabolism in, 506 ; creatin
metabolism in, 506 ; creatinine meta-
bolism in, ib. ; effect of, on metabolism,
515 ; haemopoiesis in, 518 ; proteolytic
enzyme in, of man, 528 ; glycogen in,
538 ; iron in, 547 sq. ; glycogen in,
of Rodentia, 553 ; fat in, of Rodentia,
ib. ; explusion of, 567, 579 ; area of,
after parturition, 582 ; in relation to
lactation, 612 sq. ; effect of extract on
mammary gland, 621

Placental attachment, centric, 442 ; ex-
centric, ib. ; interstitial, ib.

Placental blood formation, in Tarsius,
518 ; in Tupaia, ib.

Placental classification, 404 sq., 408 sq.

Placental folds of rabbit, 451 sq.

Placental formation, plan of, 508 sq.

Placental haemopoiesis, in rabbit, 518 ;
in mouse, ib. ; in bat, ib.

Placental metabolism in rabbit, 465

Placental villi, 394

Placotus, formation of corpus luteum in,
142

Plaice, breeding season in, 16

Planaria velata, reproduction in, 226 sq.

Plantigrades, fertility in, 630

Plant-louse, breeding season in, 10 ;
sex-determination in, 669 ; partheno-
genesis in, ib.

Plants, cross-sterility in, 215 ; fertility in,
628

Plaques amniotiques, glycogen in, 436

Plasmodiblast of shrew, 483 ; of mole,
484 ; of Tupaia javanica, 486

Platypus, cestrous cycle in, 35

Plicate placenta, 410

Plover, migration of, 23

Plurioval follicles, 122 n.

Polar body, 125 sqq. ; in rabbit, 127 ;
in pigeon, 128 ; in frog, ib. ; in Palolo
worm, 129
Polecat, cestrous cycle in, 53 ; period of

gestation in, ib.

Polychsetes, breeding season in, 10
Polyembrony, 229 ; in mammals, ib. ;
in opossum, ib. ; in armadillo, ib. ;
in Ageniaspis fuscicollis, 679
Polynce, fertilisation in, 236
Polyoestrum, 34, 66 sq.
Polycestrous animals, corpus luteum in,

^373

Polypeptides in urine, 533
Polyphemus, spermatozoa of, 168
Polypterus, phenomena associated with

breeding in, 26

Polypterus bichir, breeding season in, 16
Polypterus lapradii, breeding season in, 16
Polypterus senegalis, breeding season in, 16
Polyspermy, 183 sqq. ; in insects, 183 ;
in fishes, ib. ; in reptiles, ib. ; in earth-
worm, ib. ; in lamprey, ib. ; in axolotl,
ib. ; in fowl, ib. ; in Amphibia, 185
Polytoma as diet for Hydatina, 668
Pond-snail, breeding season in, 13
Porpoise, breeding season in, 48 ; period

of gestation in, ib.

Potassium, in egg of fowl, 278 ; in foetus of

man, 547 ; in milk, 594 ; in ash of

pup, 595 ; in milk of dog, ib. ; in serum

of dog, ib.

Praopus hybridus, sex-determination in,

679

Pregnancy, tubal, 136 ; ectopic, ib. ;
extra-uterine, ib. ; ovarian, ib. ;
absence of corpus luteum in, 378 ;
pituitary gland during, 382 ; uterine
mucosa during, 400 ; hyperglycsemia
during, 462 ; respiratory quotient
during, 465 ; tubal, in man, 492 ;
uterus of man during, 495 ; glands
during, in man, 499 ; changes in mater-
nal organism during, Chapter XI. ;
paraplegia during, 514 ; changes in
metabolism during, 518 ; calcium
metabolism during, 519 ; magnesium
metabolism during, ib. ; phosphorus
metabolism during, ib. ; nitrogen meta-
bolism during, ib. ; energy of meta-
bolism during, ib. ; energy metabolism
during, ib. ; body-weight during, 523 ;
protein metabolism during, 524 ;
metabolism during, in guinea-pig, ib. ;
absorption of protein by mother
during, ib. sq. ; metabolism during,
in dog, ib. sq. ; nitrogen balance during,
525 ; nitrogen balance during, in
rabbit, 526 sq. ; nitrogen balance
during, in dog, 526 sqq. ; nitrogen
retention during, 530 sqq. ; nitrogen
excretion during, 532 sqq. ; urine during,
534, 536 ; acetone bodies in, 535 sq. ;
acid-base equilibrium during, 536 ;
creatin in urine of, ib. ; albuminaria of,

SUBJECT INDEX

in man, ib. ; glycogen storage during,
537 ; carbohydrate metabolism during,
ib. sqq. ; excretion of carbohydrate
during, 539 sqq. ; lactosuria during,
539 sq. ; excretion of carbohydrates
during, in man, ib. ; sugar in urine
of, ib. ; glycosuria during, 539 sqq. ; •
sugar in blood of, 540 ; fat metabolism
during, 541 sqq., 544 sq. ; cholesterin
in blood of, 542 • cholesterinesters in
blood of, ib. ; glycerinesters in blood
of, ib. ; lecithin in blood of, ib. ;
acetone bodies in urine of, 544 ;
acetonuria during, 545 ; acid-base
equilibrium in, ib. ; ammonia excretion
during, 546 ; metabolism of metals
during, 547 sqq. ; metabolism of salts
during, ib. ; calcium during, 547 ;
haemoglobinaemia in, 549 ; magnesium
in, 550 ; calcium during, in dog, ib. ;
phosphorus metabolism during, in
dog, ib. ; phosphorus in, ib. sq. ; sul-
phur in, 55 i ; chloride in, ib. sq. ;
oedema in, 552 ; respiratory exchange
during, ib. sqq. ; energy metabolism
during, ib. ; oxygen consumption
during, in rat, 553 ; energy metabolism
during, in man, 554 ; energy meta-
bolism during, in dog, ib. ; hypertrophy
of liver during, 556 ; blood of dog dur-
ing, ib. ; blood of sheep during, ib. ;
hydraemia of, ib. ; blood in, ib. sq. ;
changes in maternal tissues during,
ib. sqq. ; heart during, in rat, 557 ;
ductless glands in, 558 sq. ; pituitary
during, in man, 559 ; skin during, ib. ;
meningitis during, ib. ; mammae during,
ib. ; mammary glands of man during,
608 ; growth of mammary glands in
latter part of, 618 ; corpus luteum
during second half of, 619 ; effect of
castration during, in guinea-pig, 620

Preplacental blastocyst of beaver, 423

" Prepotency," 214

Prepuce, 254

Preputial gland, 253 ; in musk deer, ib. ;
in musk rat, ib. ; in hamster, ib.

Primates, cestrous cycle in, 56 sqq. ;
ovulation in, 132 ; discharge of ova into
Fallopian tube in, 135 ; placenta of,
408, 410, 490 sqq., 509; yolk-sac
in, 425 sq. ; " Bauchstiel " of, 490 ;
" Haftstiel " of, ib. ; trophoblast
of, ib. ; chorion of, ib. ; allantois of,
ib. sq. ; decidua capsularis of, 491 ;
yolk-sac of, ib. ; uterine mucosa of,
492 ; position of mammary glands in,
586 ; teat of, 587

Proamnion, 416

Proboscidea, placenta of, 408, 450 ; yolk-
sac in, 421

Prochorion, 405 ; of Marsupialia, 405 ;
of Ungulata, ib. sq. ; of pig, 406 ; of
sheep, ib. ; of deer, ib. ; of dog, ib. ;
of ferret, ib. ; of rat, ib. ; of mole, ib. ;

of Macacus nemestrinus, ib. ; of rabbit,
451

Proline, 288, 304

Prong- buck, horns of, 25 ; rutting of, ib.
sq. See also Antilocapra americana

Procestrum, 33 ; in Tupaia javanica, 56 ;
in Carnivora, 92 ; in Marsupial cat,
106 ; in Eutheria, 107 ; purpose of,
108 ; changes during, 156 sqq.

Prostate gland, 241, 247 sqq., 268 ; in
mammals, 247 ; arteries of, ib. ; in
dog, 248 ; function of, ib. ; secretion
of, ib. sqq. ; cyclic changes in, 250 ;
atrophy of, 251 ; after castration, ib. ;
extract of, 272 ; nature of secretion of,
300 ; after castration, 320

Protamine, 303 sq., 311

Protein, in egg of fowl, 277 ; in semen,
297 ; metabolism of, 389 ; metabolism
of, in placenta, 464 ; metabolism of,
during pregnancy, 524 ; absorption of,
by mother during pregnancy, ib. sq. ; re-
quirement of, by foetus, 525 ; in milk,
594

Proteolytic ferments, 507

Proteose of colostrum, 619

Protobroque cells in oogenesis, 116

" Protones," 304

Protopterus, breeding season in, 16

Protozoa, breeding season in, 4 sq. ;
chromosomes in, 205 ; rejuvenescence
in, 221 sq. ; growth and reproduction
in, 701 ; immortality of, 724

Pseudomucin from human ovarv, 276

Pseudonuclein, 282, 290

Pseudo-plicate placenta, 411

Pseudo-pregnancy, 33 sq., 50 sq., 131, 147,
156, 576; in 'dog, 97, 102, 576; in
rabbit, 101 sq., 372, 380, 576 ; in guinea-
pig, 103 ; in Marsupial cat, 106 sq., 576 ;
corpus luteum of, 149, 576, 619 ;
corpus luteum of, in rabbit, 616 ;
in Dasyurus viverrinus after spontane-
ous ovulation, 616 sq. ; mammary
glands during, ib. ; corpus luteum of,
in dog, 617 ; mammary glands during,
in rabbit, ib. ; mammary glands during,
ib. sq.

Pterapvs, procestrous flow in, 56

Pteropus edulis, placenta of, 489 sqq. ;
decidua capsularis of, 489

Puberty, 712 sqq. ; and growth in man,
713 ; ovary at, t6. ; in horse, 714 ; in
cattle, ib. ; in pig, ib. ; in sheep, t6. ;
in dog, ib. ; in cat, ib. ; in Rodentia,
ib. ; in mouse, ib. ; in rat, ib. ; in
rabbit, ib. ; in man, ib.

" Puberty gland," 331, 386 ; in female,
347

Pudic nerves, 267

Puerperal uterus, condition of, 579 ; size
of, 581

Puerperium, 33, Chapter XII. ; urine
during, 536 ; peptonuria in, 537 ; lactose
in urine during, 540 ; sugar in blood

752

SUBJECT INDEX

during, ib. ; osteomalacia in, 549 ; in
man, 579 sqq. ; vaginal discharge in,
580 ; glycosuria in, 583 ; urine in, ib. ;
leucocyte content in, ib. ; pulse-rate in,
ib. ; temperature in, ib. ; in animals,
584 ; in Deciduata, ib. ; in monkey, ib. ;
in Carnivora, ib. ; in Rodentia, ib. ; in
Tarsius, ib. ; after abortion, ib. sq.

Pulpa? diffluente in guinea-pig, 432

Pulse-rat* during menstruation, 63 ;
during puerperium, 583

Puma, cestrous cycle in, 53 ; period of
gestation in, ib.

Purine bases, 282, 307 sqq., 312 ; in egg
of Bombyx. 293

Purpura lapillus, breeding season in, 12

Pygopagous twins in man, 610

Pyometra in menopause, 715

Pyrimidine, 308 sq., 312

Pyrrhocirus, dimorphism of spermatozoa
in, 672

Pyrrhula in captivity, 629

Pyrrol blue for vital staining, 466

Quadruplets in man, 624

Quagga, Lord Morton's, telegony in, 208

Quintuplets in man, 624

R

Rabbit, breeding season in, 37 ; cestrous
cycle in, 38 ; uterine cycle in, 100 sqq. ;
pseudo- pregnancy in, 101 sq., 372, 380,
576 ; uterine mucosa in, 102, 451 ; ovary
of, 111 ; production of ova in, 115 ;
discus proligerous in, 124 ; polar body
in, 127 ; ovulation in, 129 ; formation
of corpus luteum in, 139, 143 sq., 149 ;
atretic follicle in, 149 ; retention of
ovum in follicle of, 151 ; follicular
atresia in, 151, 153, 154 ; spermatotoxic
serum in, 164 n. sq. ; movements of
spermatozoa in, 173 sq. ; artificial
insemination in, 176 ; transplantation
of ova in, 209 ; in- breeding in, 224 ;
ovariotomy in, 347 sqq. ; hysterestomy
in, 348 ; transplantation of ovary in,
348, 350 ; effect of ovarian extract on,
356 ; ovariotomy during pregnancy in,
371 ; suprarenal glands of, 385; albumen
layer of ovum of, 406 ; yolk-sac in,
415 sq., 422 ; amnion of, 413 ; meso-
blast of, 421 sq. ; blastodermic vesicle
of, 422 517., 453 ; prochorion of, 451 ;
placenta of, 451 sqq., 457 ; gestation
sac of, 452 ; periplacental folds of, ib. •
ob-placental folds of, ib. ; ectoplacental
folds of, ib. sq. ; period of gestation in,
456 ; symplasma in, 457 ; glycogen in
placenta of, 460 sqq. ; protein in pla-
centa of, 464 ; respiratory quotient in,

465 ; placental metabolism in, ih. 5
placenta! ferments of, ib. sq. ; vital
staining in, ib. sq. ; placental haemo-
poiesis, 518 ; nitrogen balance during
pregnancy in, 526 sq. ; laevulose in
foetus of, 537 ; origin of foetal fat in,
543 ; lumbar nerves of, 560 ; mechan-
ism of parturition in, 571 ; number
of mammary glands in, 586 ; growth
of mammary gland in, 605 sqq. • foetal
extract and lactation in, 613 ; lactation
before parturition in, 615 ; corpora
lutea of pseudo-pregnancy in, 616 ;
mammary tissue of virgin, 617 ;
myometrial gland in, 618 ; mammary
glands before ovulation in, 619 ; fer-
tility in, 627 sq., 636 ; size of litters in,
625 ; foetal atrophy in, 656 ; puberty
in, 714 ; growth of, 706, 708

Raja, egg-membrane in, 289

Raja batis, dimorphism of ova in, 679

Rana arvalis, hybridisation in, 210

Rana fusca, fertilisation in, 187 ; hybri-
disation in, 210

Rana limnocharis, breeding season in, 20

Ranovin in egg of frog, 291

Rat, cestrous cycle in, 37 ; period of
gestation in, ib. ; uterine cycle in, 101,
103 ; ovulation in, 130 ; corpus luteum
of lactation in, 149 ; in-breeding in,
217 ; transplantation of testes in, 331
sq. ; ovariotomy in, 346 ; transplanta-
tion of ovary in, 351 sqq. ; ovariotomy
during pregnancy in, 370; prochorion
of, 406 ; mesoblast of, 421 ; yolk-sac
in, 422 ; trophoblast of, ib. ; placenta
of, 451 ; vital staining in, 466 ;
oxygen consumption in pregnancy
in, 553 ; heart during pregnancy in,
557 ; -ductless glands during pregnancy
in, 558 ; corpus luteum of, 620, 622 ;'
size of litters in, 624 ; sterility in
caged, 631 ; number of oocytes in
ovary of, 636 ; sterility due to alcoholism
in, 647 ; foatal atrophy in, 656 ;
sex-determination in, 669 ; puberty in,
714 ; menopause in, 717 ; longevity
in, 722

Raven, incubation period of, 23 ; lon-
gevity of, 722

Recuperation period, in menstrual cycle
of man, 82 sq. ; in menstrual cycle of
monkeys, 88 ; in uterine cycle of
Carnivora, 95 ; in uterine cycle of
Ungulata, 104 sqq.

Red-deer, cestrous cycle in, 45

Rejuvenescence, 198, 327 ; in Protozoa,
221 sq. ; in Paramcecium, 221 sq. ;
in horse, 223 sq.

Reproduction, of Stylonychia, 6 ; of
Paramcecium, ib. ; of Colpoda, ib. ;
asexual, ib. n. ; of Hydra, ib. sq. ; forms
of, 225 sqq. ; in Planar ia, 226 sq. ;
in Planar ia velata, 226 sq. ; in Ctenodrilus
monostylos, 226

SUBJECT INDEX

753

Reproductive period, length of, 623
Reptilia, breeding season in, 21 ; poly-

spermy in, 183 ; biochemistry of sexual
organs in, 289 ; longevity in, 722
Respiration, in placenta, 394, 464 sq.,

504 sq. ; during senescence, 718
Respiratory exchange, effect of castra-
tion on, 389 sq. ; during pregnancy,

552 sqq.
Respiratory quotient, of developing egg,

284 ; of mammalian embryos, 286 ;

during pregnancy, 465 ; in rabbit, ib. ;

in guinea-pig, ib. : of baby, 505 ; of

foetus in guinea-pig, 552 sq.
Rest period, in menstrual cycle of man,

74 sq. ; in menstrual cycle of monkeys,

85 ; in uterine cycle of Carnivora, 93 ;

in uterine cycle of Ungulata, 103
Rete testis, 160, 240
Retraction, mechanism of, 262 sqq.
Retractor penis muscle, 263
Rhacophorus leucomystax, breeding season

in, 20

Rhizocepkala, hermaphroditism in, 692
Rigor mortis, cause of, 728
Ring-dove, vitality of spermatozoa in,

177 ; sex - determination in, 685 ;

longevity in, 723. See also Pigeon
Rodentia, dicestrous cycle in, 34 ; oestrous

cycle in, 39 ; uterine cycle in, 100 sqq. ;

clitoris in, 261 ; placenta of, 408, 451 ;

yolk-sac in, 421 sqq. ; glycogen storage

of, in, 538 ; importance of carbohydrates

in foetus of, 545 ; glycogen in placenta

of, 553 ; fat in placenta of. ib. ; puer-

perium in, 584 ; teat of, 587 ; size of

litters in, 623 sq. ; fertility in, 629 ;

puberty in, 714

Roe-deer, period of gestation in, 43 n. sq.
Ro'ntgen rays, effect of, on testes, 330 ;

effect of, on human ovary, 347 ; as

cause of sterility, 645 sq.
Rorquals, breeding season in, 48
Round-worm, form of spermatozoa in, 169
" Royal food " of queen bee, 664 sq. ;

nitrogenous substances in, 665 ; fatty

substances in, 665 ; glucose in, ib.
Ruminants, sexual season in, 45 ; tropho-

blast in, 439 sq. ; uterine milk of, 510 ;

glyeogen in placenta of, 538 ; fertility

in, 629

Russia, sex-ratio in, 687
Ruticitta phasnicurus, intersexualitv in,

341
Rutting season, 32 sq. ; in camel, 24

Saccocirrus, fertilisation in, 184, 193
Sacculiiia, 295 sq., 691 ; effects of, on crab,

326

Sacral nerves, 270, 560
Sagartia troglodytes, breeding habit of,

8 ; longevity in, 721

Salamander, sexual activity in, 21 ; life
cycle in, 227 sq.

Salmine, 306 ; in spermatozoa, 303 ;
composition of, 304 sq.

Salmon, breeding season in, 17, 31 ;
phenomena associated with breeding
in,' 26 sq. ; periodicity in breeding in,
29 ; biochemistry of sexual organs in,
303 sqq. ; spermatozoa of, 306

Salts, metabolism of, during pregnancy,
547 sqq. .

Salt-water minnow, see Fundulus

Sanderling, breeding season in, 22

Sarcophytum, breeding season of, 8

Sauropsida, 415 ; yolk-sac of, 411

Saw-flies, sex-determination in, 667

" Schlussplatte," 396

Sciurus vulgaris, oGstrous cycle in, 38

Sclerophytvm, breeding season of, 8

Scombrine, 304, 305

Scrotum, 164 n., 165

Scyllium, egg-membrane in, 289

" Sea-grapes," 292

Seal, period of gestation in, 30 ; oestrous
cycle in, 54. See also Harp seal and
Fur seal

Season, influence of, on milk, 596 sqq.

Sea-urchin, breeding season in, 14 ;
fertilisation in, 236. See aUo under
Generic names

Sebaceous glands, 587

Secondary sexual characteristics, in cap-
tive birds, 629 ; growth of, in man, 713

Segmentation cavity, 405

Selection, gametic, 210

Self-fertility, of Cynthia partita, 215 ;
of dona inteslinalis, 216 : of Strongy-
locentrotuA. ib.

Self -sterility, of Abutihn, 215 ; of Lobelia,
ib. • of Oncidium, ib. ; of dona intes-
tinalis, ib.

Semen, 160, 169 sq. ; number of sperma-
tozoa in, 169 sq. ; effect of sexual
activity upon, 170 ; course of, 268 ;
constituent secretions of, 296 ; char-
acteristics of, ib. ; chemistry of, ib. ;
quantity ejaculated, ib. sq. ; composi-
tion of, in dog, 297 ; composition of,
in horse, ib. ; composition of, in man,
ib. ; composition of ash of, in man, ib. ;
organic substances of, 298 .
"Seminal fluid, see. Semen

Seminal granules, 164

Seminiferous tubules, 161 sqq., 241 ;

spermatogonia of, 162 ; cells of Sertoli

of, ib. sq. ; spermatocytes of, «•&. ;

spermatids of, ib.

Semnopithecus entellus, breeding season

in, 57 ; menstrual cycle in, 84 sqq.
Semnopithecus nasicus, placenta of, 491 ;

trophoblast of, 491

Senescence, 718 sqq. ; in Protozoa, 6 ;
in man, 718 sqq. ; changes consequent
upon, 718 : bones during, ib. ; muscles
during, ib. ; arteries during, ib. ; liver

754

SUBJECT INDEX

during, ib. ; kidney during, ib. ; heart
during, ib. ; urine during, ib. ; respira-
tion during, ib. ; brain during, ib. sq. ;
production of spermatozoa during, 720,
727 ; in horse, 721

Seps, formation of corpus luteum in, 145
Seps chalc.ides, yolk-sac in, 415

Serine, 288, 304

Serotina, 398, 401 ; of mouse, 469
Serum, composition of ash of, in dog, 595

Sex-differentiation in Bonellia, 692
Sex-determination, 11, 20 \, 296, 331;
Chapter XV. ; classification of theories
of, 662 ; in frog, 662 sq., 668 ; influence
of food on, 662 sqq. ; in Amphibia, 663 ;
in lamprey, 664 ; in Lepidoptera larvae,
ib. ; in fly larvae, ib. ; in bees, ib. sqq. ;
in termites, 665 ; in Nematus ventri-
cosus, ib. sq. ; in Crustacea, 666 ;
effect of fertilisation on, ib. sq. ; in
Hymenoptera, 667 ; in saw-flies, ib. ;
in Hydatina, ib. ; in Hydatina senta,
668 ; in cattle, ib. ; effect of time of
fertilisation, ib. sq. ; in man, 668 ;
in toad, 669 ; influence of nutrition
and environment on, ib. sqq. ; by
maturity of ovum, 669 ; in rats, ib. ;
in mice, ib. ; in plant-lice, ib. ; by
sexual gametes, 671 sq. ; in Tal&poria
tubulosa, 671 sq. ; by dimorphism of
spermatozoa, 672 ; in Anasa trisiis, ib. ;
in Galgulus oculatus, 673 ; XY type of,
674 ; in Drosophila, ib. ; in phyl-
loxerans, ib. n. ; in Datura, 675 ;
WZ type of, 678 ; in Lepidoptera, 678 ;
in birds, ib. ; in Myriapods, ib. ; in
Nematodes, ib. ; in spiders, ib. ; in
Mammalia, ib. ; in Praopus hybridus,
679 ; in Simocephalus, 681 ; effect of
age of parents on, 683 sq. ; effect of
parental vigour on, 684 ; effect of nutri-
tion on, 684 sqq. ; in pigeons, 685 sq.

Sex-linked characteristics, in Drosophila
ampelophila, 675 sq. ; in Abraxa
grossulariata, 676 ; in Abraxas lacticolor,
ib. ; in canaries, 677 ; in fowl, ib.

Sex-metabolism in Inachus, 691

Sex-ratio, in man, 662 ; in Todas, ib. ; in
France, 687 ; in Russia, ib. ; in Sweden,
ib. ; in London, ib.

Sex-reversal, in Crepidula fornicata, 692 ;
in Crepidula, plana, ib. ; in Triton
alpestris, 693 ; in frog, ib.

Sexual activity in male, 170

Sexual attraction in Dacus, 12

Sexual characters, secondary, 25

Sexual inversion, 691

Sexual latency, 688 sqq.

Sexual organs, biochemistry of, Chapter
VIII. ; relation of thyroid to, 384

Sexual rest, energy requirements during,
519

Sexual season, definition of, 32

Sheep, breeding season in, 24 ; dicestrous
cycle in, 34 ; cestrous cycle in, 39, 42

sq. ; practice of flushing in, 41, 634
sq. ; uterine cycle in, 103 ; uterine
mucosa in, 105 ; ovulation in, 131 ;
formation of corpus luteum in, 141 sq.,
146 ; form of spermatozoa in, 169 ;
in- breeding in, 218 ; ampulla of Henle
in, 240 ; effect of castration in, 323
sq. ; ovum of, 404 ; prochorion of,
406 ; yolk-sac in, 415, 420 ; blasto-
cyst of, 421 ; placenta of, 428 sqq.,
449, 509 ; blastodermic vesicle of,
430 ; foetal villi of, 431 ; histology
of placenta of, 435 ; fcetal nutrition in,
456 ; trophoblast of, 464 ; fixation of
blastocyst in, 509 ; laevulose in foetus
of, 537 ; blood of, during pregnancy,
556 ; uterine contraction in, 562 ;
udder of, 586 ; size of litters in, 623 ;
fertility in, 632 sqq., 696 sqq. ; barren-
ness in, 633 ; effect of food on fertility
in, 634 ; share of ram in fertility of,
635 ; inheritance of fertility in, 642
sq. ; causes of abortion in, 655 ; fcetal
atrophy in, 656 ; growth of, 707
sqq. ; puberty in, 714 ; menopause in,
717 ; longevity in, 723. See also Ovis
species

Shrew, cestrous cycle in, 55 ; formation of
corpus luteum in, 139, 145 ; placenta
of, 409, 481 sqq. ; yolk-sac in, 424;
placenta of, 481 sqq.; blastocyst of, 481;
trophoblast of, ib. sq. ; omphaloidean
syncytium of, 482 ; cytoblast of, ib. ;
plasmodiblast of, 483 ; embryo of, ib.

Siderophores, 448

Silkworm, effect of castration in, 325

Silver-sided minnow, see Menidia

Simiidse, placenta of, 408

Simocephaliis, parthenogenesis in, 670 ;
sex-determination in, 681

Sinus ensiformis, 425

Sinus terminalis, 412

Siphostoma floridoe, marsupium of, 690

Sirenia, placenta of, 408 sq., 410, 442 ;
position of mammary glands in, 586

Skin in pregnancy, 559

Sloth, position of mammary gland in, 586

Snake, phenomena associated with breed-
ing in, 28

Snipe, mating habits of, 25

Sodium, in egg of fowl, 278 ; in foetus of
man, 547 ; in milk, 594 ; in ash of pup,
595 ; in milk of dog, ib. ; in serum -of
dog, ib.

Soma, effect of, on germ-cells, 208 sqq.

Somatic stalk of yolk-sac, 415

Somatopleur, 412 ; of bat, 489

Sorex, see Shrew

Size of offspring in relation to food
supply, 522

Sparrow, breeding season in, 22 ; f ollic-
ular atresia in, 152 sq.

Sperm agglutination, in Nereis, 186 ; in
Arbacia, ib.

Spermatid, 162 sq. ; in man, 163

SUBJECT INDEX

755

Spermatocyte, 162 sq., 166

Spermatogenesis, 159 sqq., Chapter V.,
passim ; spermatocyte stage of, 162 sq. ;
spermatic! stage of, 162 sq. ; changes
during, 166

Spefmatogonia, 162, 166

Spermatotoxins, 165 n. ; in rabbit, 164 n.
sq. ; in guinea-pig, ib.

Spermatozoa, 299 ; in uterine glands,
97 aq. ; maturation of, 126, 159 ;
structure of, 166 sq. ; axial filament
of, 166 sq. ; dimorphism of, 166 n.,
168 ; achrosome of, 166 sqq. ; centro-
some of, 167 ; shape of head of, ib. ; in
Triton, 168 ; in man, 168 : middle piece
of, ib. ; tail of, ib. ; in Polyphemus,
ib. ; in Paludinct, ib. ; size of, ib. ;
form of, in bat, 169 ; in sheep, ib. ;
in frog, ib. ; in pig, ib. ; in finch, ib. ;
in ram, ib. ; in boar, ib. ; in jelly-fish,
ib. ; in monkey, ib. ; in round-worm,
ib. ; in crab, ib. ; number of, 169 sq., 296 ;
movements of, 170 sqq. ; in bat, 170 ;
in cockroach, 171 ; in Echinoidea, ib. ;
in Sphcerechinus, 172 ; in Arbacia, ib. ;
in Echinus, ib. sq. ; in rabbit, 173 sq. ;
in man, ib. ; longevity of, 177 sq. ;
in rabbit, 177 ; in dog, ib. sq. ; in
fowl, 177 ; in man, ib. ; in bat, ib.
sq. ; in Tropidonatus viperinus, 178 ;
in Salamander manulosa, ib ; in
earthworm, ib. ; in snail, 179 ; in
bees, ib. ; in ants, ib. ; path of, in
ovum, 186 ; of Strongylocentrotus, 211 ;
in-breeding and virility of, 219 ; chemo-
taxis of, 224 ; nature of fertilising
action of, 234 sqq. ; chemistry of, 302
sq. ; phosphorised fats in, 302 ; choles-
terin in, ib. ; lecithin in, 303 ; iron in,
311 ; functions of, 318 ; preservation
alive of, 649 sq. ; dimorphism of, in
Pyrrhocoris, 672 ; in Paludina, ib. ; in
Anasa tristis, ib. ; in Galgulus oculatus,
673 ; in Lygceus bicrucis, ib. ; in pig,
678 n. ; in horse, ib. ; formation of,
during senescence, 720, 727

Spermine, 299 sq., 328

Spermophilus, formation of corpus luteum
in, 145

Sphcerechinus, movements of spermatozoa
in, 172

Sphcerechinus granularis, chemistry of
spermatozoa of, 306

Sphincter vaginae, 267

Sphingomyelin, 274

Spider, sex-determination in, 678

Spider crabs, parasitic castration in, 326

Spiny mouse, see Acomys caharinus

Splanchnopleur, 412, 414 ; of bat, 489

Sponges, hermaphroditism in, 688 sqq.

Spongiosa of man, 498

Squirrel, see Sciurus vulgaris

Stalchen, 437, 439, 441

Stag, antlers of, 25, 46 ; rutting of, ib. ;
effect of castration on, 321

Starfish, 318 ; breeding season in, 14 ;
aids to fertilisation in, 229

Starling, incubation period of, 23

Stearic acid in yolk of egg, 283

Stearin in milk, 594

Stegomya, 12 n.

Stenops, clitoris in, 261

Stereozilien, 398

Sterility, 248 ; in confined animals, 5 ;
in Death's-Head hawk moth, 11 ; in
hybrids, 210 ; of mule, 211 ; of Echinus
crosses, ib. ; in horses, 216 ; and
in- breeding, 216 sqq. ; caused by per-
sistent corpora lutea, 374 ; due to
captivity, 628 sq. ; in Indian elephant,
628 ; cause of, in bears, 629 ; in hawk,
ib. ; in birds, 629 sq. ; in caged rats,
631 ; due to overfeeding in horses, ib. ;
caused by excess of sugar, ib. ; caused
by excess of molasses, ib. ; caused by
excess of linseed, ib. ; in cattle, 631,
641 ; caused by fatness, 632 ; in mice
due to fatness, ib. ; in man, ib. ; effect
of in-breeding and cross-breeding on,
639 ; between genera, 640 ; between
species, ib. ; in Drosophila, 641 ; of
hybrids, ib. ; cause of, in hybrids, 642 ;
of horse-zebra cross, ib. ; causes of,
644 sqq. ; syphilis as cause of, 645 ;
epididymitis as cause of, ib. ; due
to X-rays, ib. sq. ; causes of, in
man, 646 ; causes of, in cattle, ib. ;
causes of, in horse, ib. ; due to con-
tagious granular vaginitis, ib. ; due
to alcoholism in rats, 647 ; overcoming
of, by artificial insemination, 647 sqq. ;
importance to breeding industry, 658 ;
' in horses, ib.

Stickleback, phenomena associated with
breeding in, 28

Stoat, cestrous cycle in, 53 sq. ; interstitial
cells in ovary of, 120 n.

Striated border of syncytium, 397

Stronglocentrotus, oxidation in ovum of,
188, 191 ; fertilisation in, 194 sq. ;
prepotency of spermatozoa of, 211 ;
hybridisation of, 212 sq. ; self -fertility
in, 216

Strongylocentrotus purpuratus, 314, 318 ;
parthenogenesis in, 232

Strychnine as cure for impotence, 638

Stychostemma asensoriatum, breeding sea-
son in, 9

Stylonychia, conjugation in, 221

Stylonychia pustulata, rate of fission in, 6

Sugar, in egg of fowl, 277 ; in urine of
pregnancy, 539 sq. ; in blood of preg-
nancy, 540 ; in blood of labour, ib. ;
in blood of puerperium, ib. ; formation
of, in milk, 602 sqq. ; sterility caused by
excess of, 631

Suidae, fertility in, 628

Sulphur in pregnancy, 551

" Summer cells " of frog, 385

Superfcetation, 154 ; in cat, ib.

756

SUBJECT INDEX

Superpurgation as cause of abortion, 654

Suprarenal gland, in rabbit, 385 ; cor-
relation of, with sexual organs, ib. sq. ;
effect of castration on, 386

Swan, longevity in, 722

Sweat glands, 587

Sweden, sex-ratio in, 687 ,

Swift, breeding season in, 23

Swiftlet, see Collocalia

" Sympexions ?' of Robin, 298

Symplasma, 418, 445 ; in rabbit, 457 ; in
dog, ib. : in mouse, 467 ; in guinea-pig,
473 ; in man, 502

Synapsis in Lygceus bicrucis, 673

Synaptenic stage of otigenesis, 116 sq., 155

Syncytium, 397 sq. ; striated border of,
397 sq. ; function of, 398 sq. ; origin of,
402 ; of cat, 444 sq. ; of dog, ib. ; of
man, 494 sq., 502

Syphilis as cause of sterility, 645

Tadpoles, effect of pineal extract on, 384
Talceporia tubulosa, sex-determination in,

671 sq. ; dimorphism of ova of, 672
Talpa, clitoris in, 261
Tamandua, placenta of, 442
Tanager, phenomena associated with

breeding in, 27
Tarsius, formation of corpus luteum in,

139, 145; "Haftstiel" of, 423;

placenta of, 440 ; placental blood

formation in, 518 : puerperium in,

584
Tarsius spectrum, cestrous cycle in, 56 ;

menstrual cycle in, 91 ; ovulation and

menstruation in, 132
" Tata-eggwhite " in white of egg, 287
Taurin, 551

Tautogolabrus, life cycle in, 227
Teat, 587 ; of Carnivora, 587 ; of Ungu-

lata, ib. ; of man, ib. ; of Primates,

ib. ; of Rodents, ib. ; of Marsupials,

ib. ; of Cetacea, ib. ; size of litter in

relation to number of, 624
Telegony, 207 sq. ; in Lord Morton's

quagga, 208 : experiments on, ib.
Teleosts, breeding season in, 15 ; corpus

luteum in, 146

Temperature in puerperium, 583
Temporal gland of elephant, 253
Tenrec, see Centetes ecaudatus
Tenthredinidae, 126 n.
Tergipes, breeding season in, 14
Termites, sex-determination in, 665
Testis, Chapter V., passim ; structure of,

159 sqq. ; tunica vaginalis of, 159 ;

mediastinum of, ib. sq. ; seminiferous

tubules of, 160 ; reta testis, ib. ;

interstitial cells of, ib. sq., 163, 335 sq, ;

tunica albuginea of, ib., 161 ; descent

of, 164 n., 165 ; correlation of male

characters with, 320 sqq. ; and

secondary sexual characters, 321 sqq. ;
interstitial cells of, in guinea-pig, 330 :
effect of Rontgen rays on, ib. ; of
woodchuck, 331 ; transplantation of, ib.
sqq. ; compensating hypertrophy in,
338 sq. ; relation of thymus to, ^79 ;
conclusions regarding internal secretion
of, 386 sqq,
Tetanus uteri, 563
Tetany, 385

Tetheh'n as prolonging life, 712
Telraceros, placenta of, 432
Tetrad, 125 n. '
Tetronerythrin, 294 sq.
Theca externa, 121 ; of dog, 110
Theca interna, 121 ; of dog, 110
Thelyplasm, 690

Thymectomy, in guinea-pig, 379 sq. ; in
rabbit, 380 ; in fowl, 380 ; in dog, ib.
Thymine, 308 sq.
Thymus, relation of, to testes, 379 sq. ;

effect of castration on, 379
Thyroid gland, relation of, to sexual

organs, 384
Thyroidectomy, 385
Tiger, period of gestation in, 53
Timor pony, cestrous cycle in, 46
Toad, breeding season in, 18 ; oviposition
in, 135 ; ferment of gonads in, 318 ;
sex-determination in, 669. See also
Foetid toad and Fire-bellied toad
Todas, sex-ratio among, 662
Tortoise, phenomena associated with

breeding in, 28 ; longevity in, 722
Toxaemias of pregnancy, 392, 533 sq., 546
" Trager," 468

Transplantation, of ova, 209 : ovaries, tb.
Traumatisms, 375
Tree-frog, breeding season in, 18
Trichosurue, breeding habit of, 67
Trichosunts vulpecula, breeding season in,

36

Triplets in man, 624
Triton, spermatozoa of, 168
Triton alpestris, hybridisation in, 210 ;

sex -reversal in, 693
Triton waltlii, breeding season in, 20
Tropidonatus, egg-membrane in, 289
Trophoblast, 402, 405, 407, 409 sq., 508
sq. ; of mouse, 422 ; of rat, ib. ; of
horse, 429 ; of pig, 428 ; inter-cotyle-
donary, in cow, 432 ; in ruminants,
439 sq. ; of sheep, 464 ; absorption
of haemoglobin by, ib. ; of beaver, 476 ;
of hedgehog, ib. sqq. ; of shrew, 481
sq. ; of Tupaia javanica, 485 sq. •
of bat, 487, 489 ; of Primates, 490 ;
of Semnopithecus nasicus, 491 ; of
man, 494, 496 sq., 499
Trophocyst of mole, 484 sq.
Trophosphere of hedgehog, 478
Trophospongia, of hedgehog, 478 sq. ;

of Tupaia javanica, 486
Trophoblastic activity, nature of, 509 sqq.
" Trypanblau," see Trypan blue

SUBJECT INDEX

757

Trypan blue, for vital staining, 465 sq. ;
order of staining of fcetal organs bv,
466

Tubal pregnancy, 136 sq.

Tunica albuginea. 159

Tunica vaginalis, 159

Tupaia, formation of corpus luteum in,
139, 145 ; clitoris in, 261 ; placenta of,
409, 485 ; placenta! blood formation
in, 518

Tupaia javanica, 406 ; procestrum in, 56 ;
uterine cycle in, 92 : yolk-sac in, 424 ;
blastocyst of, 485 ; placenta of, 485
sq. ; " Haftflecke " of, ib. ; trophoblast
of, ib. ; plasmodiblast of, 486 ; cyto-
blast of, ib. ; trophospongia of, ib. ;
permanent placenta of, ib.

Turbellaria, fertilisation in, 184

Turkey, fertility in, 628

Turpentine, abortion by, 652

Twins, in man, 624

Tyramine, 392

Tyrosine, 288, 304

U

Udder, 586 ; milk cisterns of, ib. ; of
cow, ib. ; galactophorous sinuses of,
ib. ; teats of, ib. ; quarters of, ib ;
extra teats of, ib. ; of sheep, ib.

Ungulata, cestrous cycle in, 39 sqq. ;
uterine cycle in, 103 sqq. ; prochorion
of, 405 sqq. ; placenta of, 408, 410, 427
sqq., 509 ; yolk-sac of, 420 ; embryonic
shield in, ib. ; fat in uterine milk of,
542 ; position of mammary glands in,
586 sq. ; Ijjats of, 587 ; size of litters
in, 623

Uracil, 308

Urea, 532 sq. ; excretion of, 534

Urethra, 241 ; structure of, 253

Urine, nitrogen in, 532 sq. ; polypep-
tides in, 533 ; creatin in, ib. ; during
pregnancy, 534, 536, 539 sq. ; during
puerperium, 536, 583 ; sugar in, during
pregnancy, 539 sq. ; lactose in, during
puerperium, 540 ; acetone bodies in,
during pregnancy, 544 ; phosphorus in,
551 ; during senescence, 718

" Uterine," 377

Uterine contraction, mechanism of, 561
sqq. ; in sheep, 562 ; in cat, ib. sq. ; in
rabbit, 563 sqq.

Uterine cycle, in Lemurs, 91 ; in Tarsiua
spectrum, ib. ; in Insectivora, 92 ; in
Tupaia javanica, ib. ; in Galeopithecus
volans, ib. ; in Carnivora, ib. sqq. ;
in dog, ib. ; in ferret, ib. ; of ferret,
period of rest in, 93 ; of ferret, period
of growth in, 93 sq. ; of ferret, period
of destruction in, 94 sq. ; of ferret,
period of recuperation or repair,
95 sq. ; in Rodentia, 100 sqq. ; in
rabbit, ib. ; in marmot, 100 ; in

Muridae, ib. ; in rat, 101, 103 ; in
guinea-pig, 101 sq. ; in Ungulata,
103 sqq. ; in sheep, 103 ; in pig, 103,
106 ; of pig, period of rest in, 103 ;
of pig, period of growth in, 103 sq. ;
of pig, period of destruction in, 104 ;
of pig, period of recuperation in, 104
sqq. ; in Marsupials, 106 sqq. ; in
Marsupial cat, 106

Uterine glands, 73, 408 ; of man, 502
Uterine involution, 581 ; castration and,

582

Uterine milk, 410, 429, 432 sqq. ; blood in,
434 sq. ; fat in, 435 ; composition of,
436 sqq.; " Uterinstabchen " of, 437;
changes in, 438 ; in Ruminants, 510 ;
fat of, in Ungulata, 542
Uterine mucosa, 407 sq., 417, 432 ;
human, 77, 81 ; pigment of, 97 ; in
dog, 99, 102 ; in rabbit, 102 ; in sheep,
105; hypertrophy of, 370; effect of
ovariotomy on, 376 ; during pregnancy,
400 ; in pig, 428 ; crypts of, 442 ; of
dog, 443 ; of rabbit, 451 ; of Primates,
492 ; of man, ib.
Uterine sinuses, region of, 454
Uterine stroma, renewal of, 581
Uterinstabchen, 4 ; of the uterine milk,

437

Uterus, changes in, during oestrous cycle,
Chapter III., passim; connection of, with
peritoneum, 71 ; human, 72 ; structure
of, ib. sq. ; glands of, 73, 408 ; peristalsis
of, 173 sq. ; supposed internal secretion
of, 376 sqq. ; absence of, 379 ». ; during
pregnancy in man, 495 ; condition of
puerperal, 579 ; size of puerperal, 581
Uterus masculinus, 241, 270 ; in man, 242 :
in goat, ib.

Vagina, 71 ; structure of, 73, 75 ; involu-
tion of, 582

Vaginal discharge of puerperium, 580

Vallisneria, 19

Variation, and conjugation, 198 ; purpose
of, 199

Vas deferens, 160, 239 *'q., 268 sqq. ;
length of, in man, 239

Vasectomy, 327 ; effect of, on vesiculse,
246 ; effect of, 331 sq.

Vas efferens, 159 sq., 239, 268 sqq.

Vesicula seminalis, 240, 243 sqq., 268 sq. ;
in hedgehog, 55 n., 244 sq. ; function
of, 243 ; in guinea-pig, ib. ; in mole,
ib. ; in Cervus alces, 245 ; secretion
of, 245 sqq. ; after castration, 246 ;
after vasectomy, ib. ; nature of secre-
tion of, 300

Vesiculase, 245, 301

Vespertilio, formation of corpus luteum in,
142

758

SUBJECT INDEX

Vesperugo, formation of corpus luteum in,
142, 145 ; retention of ovum in follicle
of, 151

Vesperugo noctula, see Bat

Vicia, chromosomes of, 206 •

Villi, structure and function of, 396 sqq. ;
core of, 398

Virgin, mammary tissue of, 617 ; explana-
tion of lactation by, ib.

Vitab'ty of gametes, 220

Vital staining, of placenta, 465 sq. ;
with trypan blue, ib. ; in rabbit, ib. ;
with pyrrol blue, 466 ; in mouse, ib. ;
in guinea-pig, ib. ; in rat, ib. ; in cat,
ib. ; with Indian ink, ib.

Vitamins, 529 sq.

Vitellin, 281 sq., 286, 293 ; composition
of, 288

Vitelline membrane, 184

Vitellolutein in eggs of M aja squinado, 294

Vitellorubin in egg of Maja squinado, 294

Vocal cords, growth of, 713

Vole, see Arvicola glareolus

" Vollplacenta," 409

Vulva, 74 ; innervation of, 560

W

Walrus, oastrous cycle in, 45, 54 ; period

of gestation in, 45, 55 ; lactation period

in, 55

Wapiti deer, oastrous cycle in, 45
Water-buck, cestrous cycle in, 45
Water shrew, cestrous cycle in, 55
Water-soluble vitamin B, experimental

importance of, 529 sq.
Weasel, oestrous cycle in, 53 sq.
Weather, influence of, on milk, 596
" Wellenbewung " hypothesis, 61 sq.
Whale, periodicity of breeding in, 29 ;

oestrous cycle in, 47 ; breeding season

in, ib. sq.

Whey albumen in milk, 594
White of egg, composition ' of, 277 aq. :

glucoprotein in, 287 ; ovamucoid in,

ib. ; ovalbumen in, ib. ; conalbumen

in, ib. ; " Tata-eggwhite," ib.
WiM cat, oestrous cycle in, 52 ; period of

gestation in, ib. ; breeding season in,

ib.

Wild-duck, fertility in, 628
" Witch's milk," 595, 615
Wolf, breeding season in, 4 ; cestrous

cycle in, 50 ; period of gestation in, ib.
Wolffian body, 114
Woodchuck, interstitial cells in testis of,

163 ; testes of, 331
" Work of development," 285
Wrasse, see Ctenolabrus
WZ type of sex-determination, 678

Xanthine, 307

Xanthophyll, 281

X-chromosome in Lygceus bicrucis, 673

" Xenia," 208

Xenia hicksoni, breeding season in, 8

Xenopus, breeding season in, 19 sq.

Xenopus Icevis, breeding season in, 19

X-rays, effect of, on germ - cells, 209 ;

sterility due to, 645 *q.
XY type of sex-determination, 674

Yak, oestrous cycle in, 45. See also Bibos
grunnicus

Y-chromosome in Lygceus bicrucis, 673

Yew, abortion caused by, 652

Yohimbine as cure for impotence, 638 ;
effect of, on genital organs, 638 sq.

Yolk of egg, composition of, 277 sq. ;
colour of, 283 ; palmitic acid in, ib. ;
oleic acid in, ib. ; stearic acid in, ib. ;
lecithin in, ib. ; lutein in, ib.

Yolk-sac, Chapter X., Part 3 ; origin
of, 411 ; of Sauropsida, ib. ; somatic
stalk of, 415 ; of Lacertilia, ib. ; in
sheep, ib. ; in Seps chalcides, ib. ; in
man, ib. ; nutritive importance of,
415 sqq. ; in opossum, 415 ; in rabbit,
415,422; of Marsupialia, 416; nutri-
tive importance of, in Ungulata, 420 ;
in horse, ib. • in cow, ib. ; in pig, ib. ;
in sheep, ib. ; in Carnivora, ib. ; in
dog, 421 ; in elephant, ib. ; in Probos-
cidea, ib. ; in HyraA, ib. ; in Rodentia,
ib. sqq. ; in mouse, 422 sq. ; in rat,
422 ; in Acomys caharinus, 423 ;
in hedgehog, 424 ; in shrew, ib. ; in
Insectivora, ib. sq. ; in mole, ib. ;
in Tupaia javanica, ib. ; in bat, 425 ;
connecting stalk of, ib. ; in monkey, ib. ;
in Primates, ib. sq. 491 ; in man. ib.

Yolk-spherules, 291

Yolk-villi, 424

Zebra, sterility of hybrid, with horse, 642

Zebu, see Bos indicus

" Zellsaiilen," 396 ; of man, 500 sq.

" Zenker's crystals," 299

Zoarces, formation of corpus luteum in,

145
Zona pellucida, 121, 404, 405 sq. ; of

hedgehog, 476

Zoua radiata, 121. See also Corona radiata
Zonary placenta, 408, 442
Zonary villi of ovum, 445

INDEX OF AUTHORS

Abderhalden, 517, 595

Abel, 376

Abel and M'llroy, 561

Abelous and Heim, 295

Ackroyd and Hopkins, 309

Acton, 296

Adams, 55, 56

Adler, 578

Adolphi, 170, 173

Agassiz, 16

Ahlfeld, 403, 523

Akutsu, 269

Albers-Schonberg, 645

Albertoni, 20

Albrecht, 175, 649

Albrechtsen, 374

Albu and Neuberg, 278, 290

Allen, 119, 147, 161, 541, 631

Allen, L. M., 578

Allison, 224, 684

Alquier and Thauveny, 384

Amanted, 170

Ancel and Bouin, 101, 114, 149, 339, 371..

577, 611, '616, 618, 620
Andrews, 356, 370
Annandale, 6 sq., 20, 631
Annandale and Robinson, 65
Apfelstedt and Aschoff , 503
Arai, 636

Aristotle, 15, 41 sq., 59, 627
Arrhenius, 59

•Arkell and Davenport, 323
Aschner, 362, 383
Ascolip, 464, 507
Ashworth, 8

Ash worth and Annandale, 8, 721
Asimi, 152
Assheton, 106, 406, 408 sq., 411, 420 sq.,

423, 427 sq., 430 sqq., 438 sq., 441, 450,

453, 512

Athias, 114, 128, 152, 347, 577, 620
Atkins, 120
ACwater, 525
Axe, Wortley, 569, 656

B

Babcock and Clausen, 641 sq., 657, 661

Backhouse, W. O., 51, 154

Von Baer, 111, 138, 228

Balbiani, 670

Balfour, 112 sq., 120, 415

Ballerini, 504

Ballowitz, 167 sq., 172

Baltzar, F., 206

Baltzer, 692

Bang, B., 654

Bang, I., 306

Banta, 694

Bar, Paul, 519 sqq., 525 sqq., 531 sq., 544.

551

Bar and Daunay, 524, 526, 529
Barber, M. A., 189
Barberio, 302
Barcroft, 553
Bardeleben, 140, 300
Barnett-Hamilton, 27
Barrington, 51, 252 sq.
Barry, D. T., 159
Barry, M., 159, 180
Basch, 593, 609
Basso, 506
Baum, 523

Bataillon, F., 186, 210, 234, 316
Bates, 641

Bateson, 199, 203, 673
Bateson and Punnett, 200, 677
Bateson and Thomas, 689
Beard, 107, 157, 365 sq., 574 sq., 666, 672,

679

Bechterew, 271, 572
Beck, 173
Beddard, F. E., 39
Beebe, 27

Beigel and Schulin, 138
Bell, Blair, 63 517., 80 sq., 100 sq., 136,

349, 377 sqq., 382 sq., 385 sq., 389
Benckiser, 138
Bende, 163

Bendix and Elstein, 311
Benecke, 56, 131
Benedict, 309
Benedict and Talbot, 505
Van Beneden, 56, 125, 180, 404, 413, 437

487, 495

Van Beneden and Julin, 113, 131
Benkiser, 347
Benthin, 540

Bergell and Liepmann, 507
Bergsma, 540 sq.
Bergtold, 23
Berizowiski, 325
Berman, 326
Bernard, 327, 460
Bernhard, 556
Bert, 602
Berthold, 326
Bestion de Camboulas, 356
Beyer, 710

759

760

INDEX OF AUTHORS

Biach and Hulles, 384

Biancardi, 552

Biedl, 332, 386

Biedl and Koenigstein, 619

Bienenfeld, 504

Birnbaum, 552

Birnbaum and Osten, 63

Bischoff, 43, 50, 138, 142, 144, 170, 406,

421, 432, 452, 472
Bjorkenheim, 492
Blackman, 222
Blaine, 721
Blakeslee, 675
Blandford, 59
Blat, 539

Bles, 5, 18 sqq., 631
Bloch, 638, 652, 691
Blumreich, 557
Bocarius, 302
Bodio, 662
Bohr, 285 sq., 463 sqq., 475, 511, 515, 538

sq., 543 sq., 552 sq.
Bohr and Hasselbalch, 283 sq.
Bohr and von Davidoff, 160
Bond, 335, 377 sq., 694
Bondi, 504

Bondzinski and Zoja, 287
Boni, 552

De Bonis, 248, 250 sq., 329
Bonnet, 94, 104 sq., 177, 398, 400, 405 sq.,

413, 420, 434, 436 sqq., 444 sq., 455,

457, 502, 505, 549
Bordet, 225
Boring, 335

Boring and Morgan, 335
Boring and Pearl, 335, 693
Born, 662 sq.
Born, Gustav, 366
Boruttau, 338
Bos, 217
Bossi, 177
Boston, 379
Bottazzi, 507

Bouin and Ancel, 114, 329 sq., 338
Bouin, Ancel, and Vallemin, 646
Bourne, 9

Boveri, 180 sqq., 125, 165, 204, 702
Brachet, 264, 359, 514, 571
Brachet, A., 185
Braem, 692
Bramman, 163, 167
Branca, 630
Brandt, 341
Breschet, 59
Breuer and Seiler, 392
Bridge, 15

Bridges, 674 sq., 694
Briggs, 664
Brinkmann, 415
Brocard, 540 sq.
Van der Brock, 449, 580
Brooks, 198

Brouha, 587, 592 sq., 605
Brown and Osgood, 645
Brown-Sequard, 327, 354 sq., 574, 645

Viscount Bryce, 327

Bryce, T. H., 426, 468, 473, 501

Bryce and Teacher, 133, 403, 479, 492,

494 sqq., 499, 505
Brumpt, 570

Buchner, P., 184, 193. 612
Buchtala, 290
Buckley. 21

Bucura, 347, 364, 386, 691
Budge, 265 sq., 269 sq., 563
Budgett, 16, 26
Buffon, 627
Buhler, 146
Buller, 171 sqq., 225
Bulloch and Sequeira, 385
Bullock, 518
Bullot, 234

Bunge, 278, 283, 506, 548, 595
Burckhard, 467
Burlando, 537
Burns, 288

Burian and Schur, 309
Burrian, 302, 311, 318
Burton, 57
Buys and Vandervelte, 347

Caldwell, 35

Calkins, 6, 221 sq.

Call and Exner, 138

Calzolari, 381

Camus and Gley, 248, 301

Camerer and Soldener, 546

Cameron, 400

Campbell, Malcolm, 368

Campbell and Watson, 631

Capaldi, 541, 543

Carmichael, 350

Cannichael and Marshall, 347, 356, 358

369, 378
Carnegie, 53

Carnot and Deflandre, 63
Carpenter and Murlin, 519, 554
Carr-Saunders, 689
Castle, 215, 644, 680, 689, 691
Castle, Carpenter, Clark, Mast, and

Barrows, 217
Castle and Morgan, 216
Castle and Philips, 209
Catlin, 45
Caton, 322

Cesa-Bianchi, 114, 156
Chadwick, 14
Chambers, R,, 189
Champneys, 80
Champy, 692, 700
Charrin, 548
Charrin et Goupil, 507
Charrin and Guillemont, 538
Chauffard, Laroche et Grigaut, 274
Chelchowski, 178
Child, 9, 225, 661, 712

INDEX OF AUTHORS

761

Chipman, 403, 451 sq., 454, 455 sqg.,

459 sqq., 511
Christ, 79
Chun, 228
Des Cilleuls, 336
Cimorini, 381
Clark, 114, 133, 140 sq.
Cocks, A. H., 51 sq., 54
Codet, 460

Cohen, E. J., 216, 298
Cohn, 144, 301
Cohnstein, 556

Cohnstein and Zuntz, 462, 464, 552
Cole, 258

Cole and Bachhuber, 209
Compte, 382
Conklin, E. G., 190, 205
Cook, 12
Cooper, 632, 720
Copeman, 329, 679
Copeman and Parsons, 684
Corner, 106, 121, 128, 136, 144, 147 sq.,

274. 332, 645

Corner and Ausbaugh, 130
Correns and Goldschmidt, 661 •
Correns, 199, 673
Coryllos, 83
Coste, 394
Courant, 254
Cramer, A., 503
Cramer, H., 360, 515
Cramer, W., 275, 280, 310, 348, 522, 529

sq., 552, 555

Cramer, Drew, and Mattram, 529, 532
Cramer and Lochhead, 556
Cramer and Marshall, 390, 522, 638
Cramer and Pringle, 555
Crampton, 325
Creighton, 401
Crew, 164, 663, 693
Cristalli, 541
Cron, 540

Groom, Halliday, 59
Crowe, Gushing, and Homans, 383
Crowther, 596 sqq.
Cruickshank, 279
Cuenot, 663 sq., 669
Cull, 222

Cunningham, D. J., 50 sq.
Cunningham, J. T., 25 sq., 146, 165, 321,

333

Cunningham, R. G., 449 sq.
Curtis, 162, 644, 689
Gushing, 383
Cushny, 562, 564

Names with De and Des are indexed under
the name following.

Daels, 370, 638
Daniel, 578
Darbishire, 201

Darwin, 4 sq., 26 sq., 208, 214. 216, 224,

321, 325; 340, 564, 628 sqq., 639 sq.
Darwin and Wallace, 640
Dastre, 503
Davenport, 209
Dawson, 679
Dean, Bashford, 16
Delage, 236 sqq., 315
Delage et Goldsmith, 317
Delestre, 148, 152
Dembo, 564
Dewar and Fin, 642
Dewitz, 171
Dibbelt, 550
Disse, 469 sq.

Disselhorst, 240, 243,' 252, 256, 712
Dixon, 299, 329
Dixon and Taylor, 557
Doering, 140 sq.
De Dominicis, 302
Doncaster, 51, 126, 131, 166, 211, 219 sq.,

296, 667

Doncaster and Marshall, 679
Donaldson, 703, 706, 711, 714, 717, 723
Doran, 359, 377
Drahn, 98
Driesch, 182, 702
Driessen, 471, 503
Drips, 148
Dubner, 556
Dubois, 293, 316
Dubreuil and Regaud, 154, 371
Duckworth, 324
Dudley, 348, 360, 716
Duerden, 337, 344
Dues berg, 126
Diihrssen, 152, 177
Duncan, Matthews, 60, 624, 626, 646
Dungern, 172, 229
Durham, 677
Diising, 668, 680
Dussogno, 68
Duval, 56, 421, 432, 443 sqq., 448, 451,

453 sqq., 467, 469, 472, 474 sq., 489, 518,

584

Duval and Hubrecht, 396
Duval and Sobotta, 496
Dzierzon, 666

East and Jones, 216 sq.

Von Ebner, 590 sq., 593, 607

Eccles, McAdam, 332

Eckhard, 262, 265, 268, 609

Eden, 458, 503, 575

Ver Eeke, 524, 526, 550

Ehrlich, 556

Ehrstrom, 305, 537, 551

Eimer, 56, 131, 171, 178

Elford, 177

Ellenberger, 42 sq., 46, 104

Ellis, Havelock, 57, 59, 61, 65 sq., 691

Emge, 546

762

INDEX OF AUTHORS

Emrys-Roberts, 43, 104, 157, 286, 463

Enriques, 198, 220, 222

Engelmann, 76, 78

Engstrom, 557

Ercolani, 395, 401, 433, 487

Erdheim and Stumme, 382, 559

Erlandsen, 279

Escher, 273

Eschricht, 394

Essen-holler, 370

Evans and Bishop, 714

Ewart, 46 sq., 104, 131, 154, 208, 219, 420.

429, 578, 653 sq., 658
Ewing, 520
Ewing and Wolf, 533
Exner, 246

Falk and Hesky, 533

Falls and Walker, 518

Farkas, 293

Farmer, 184, 207

Favre, 395

Fehling, 525, 542, 546, 556

Feldman, 414, 465, 505, 562 sq., 702, 713

Fellner, 564

Ferroni, 507, 541

Fetzer, 548

Fick, 205, 270

Fichera, 381

Findley, 79 sq.

Fingerling, 280

Fischel, 536

Fischer, E., 288

Fischer and Ostwald, 318

Fitzsimon, 337

Flatau, 370

Flattley and Walton, 31

Fleming, 46, 151 sq., 569, 646, 655, 717

Florence, 301

Flower and Lydekker, 40, 587

Foa, 384

Foche, 208

Foges, 333

Fogge, 269

Foote and Strobell, 672

Fordyce, 69, 600

Forel, 691

Fortayn, 585

Foster, 573, 727

Fothergill, 403

Foulis, 114

Fowler, 322

Fox, 14. See Fuchs, H. M.

Fraenkel and Cohn, 366

Fraenkel, 69, 114, 133, 209, 363, 366 sqq.,

389, 618

Franck, 466, 568 sq.
Franck-Albrecht-Goring, 578
Francois-Franck, 262, 266
Frank, 164, 465
Frankenhauser, 563
Franz, 562, 651

Frazer, 65

Freund, 384, 517, 558 sq.

Freyer, 103

Fridericia, 282

Friedlander, 581

Fries, 54

Frommel, 401, 518

Fuchs, H. M., 211, 216. See Fox, 14

Furbringer, 247, 300

Von Fiirth, 292, 300

Von Furth and Schneider, 507, 559

Gadow, 18, 21 sq.

Galabin, 60, 78, 81, 133, 155, 566 sq., 653

Galimard, 291

Gamgee, 279, 433

Garrod, 259

Garner, 57

Gaskell, 265, 384

Gassner, 523, 580 sq.

Gautier, 174 sq.

Gavin, 596, 599, 600, 621

Gawronsky, 561

Gebhard, 79, 80, 82 sq., 84

Geddes, 324

Geddes and Thomson, 28, 158 sq., 169,

198, 661, 665 sq., 683 sqq., 689
Gegenbaur, 111, 138
Geist, 83

Gellhorn, 69, 608, 615
Gellin, 381
Gerhardt, 135, 256
Gerlach, 127
Geyelin, 627
Geyl, 575

Giacomini, 145, 415
Giacosa, 290
Giard, 228
Gierke, 538
Gies, 234, 316
Gilbert, 258

Gilchrist and Jones, 596
Giles, 62, 580

Gilliatt and Kennaway, 534
Girard, P., 189
Girard and Audubert, 213
Girtanner, 394
Glass, 348, 360
Gley, 252, 320
Glynn, 385
Godman, 61, 205
Goetsch, 383
Gofton, 137
Gohre, 490
Goldmann, 466

Goldschmidt, R., 661, 672, 694
Goltz, 264, 358, 514, 571
Goltz and Ewald, 358, 514, 571
Goltz and Frensberg, 264
Goodale, 334, 336, 341 sqq., 644, 699
Goodale and M'Mullen, 644
Goodsir, 394 sq.

INDEX OF AUTHORS

763

Gordon, 24, 359, 645 sq.

Gottschalk, 502

Gottschau, 385

Gould, 692

Gowen, 599

De Graaf, 262

Graefe, 370

Graefenberg, 528

Gray, J., 184, 213, 300

Gregerson, 280

Grassi and Sandias, 665

Graves, 377

Grigorieff, 348, 350

Grinnell, 27

Grohmann, 44

Gruber, 246

Gruenhagen, 264

Von Guaita, 217

Gudernatsch, 381, 689

Gudger, 690

Guggisberg, 577

Guillot, 543

Guldberg and Nansen, 48

Gunther, 176, 262

Gurber and Grunbaum, 537

Gurney, 340, 722

Guthrie, 209, 350

Guthrie and Lee, 351

Guyer, 126, 164 sq., 168, 316

H

Haddon, 638, 652

Hagemann, 49, 526 sq.

Hahl, 530

Halban, 350, 360, 362, 516, 559, 611 sqq.,

615

Haldane, 48

Haldane and Pembrey, 390
Hall, 505

Hall, Stanley, 714, 720
Haller, 432 sq.
Halliburton, 594
Hainan and Marshall, 380
Hamburger, 606
Hammarsten, 276, 290 sq.
Hammond, 42, 136, 149, 154, 218, 372,

375, 382, 452, 460, 577, 604 sq., 615,

618 sq., 621, 627, 636 sq., 639, 647.

656 sq., 695, 709
Hammond and Marshall, 101 sq., 372.

460, 616 sq.
Hanau, 333
Handmann, 719
Harding, 538, 544
Hare, 64
Harms, 320, 338
Harper, 134, 136
Harrison, 627, 694
Hart, Berry, 164, 689
Hart and Gulland, 401
Hartung, 278

Harvey, W., 180, 393, 432, 723
Harvey, N., 185

Hasselbalch, 286, 505

Hasselbalch and Gammeltoft, 546

Hausmann, 130

Haycraft, 65

Head, 61, 254

Heape, 24, 29 sqq., 35, 38 sq., 43, 45,

49 sqq., 53, 57, 64, 68, 74, 81, 84 sqq.

123 sq., 128 sq., 131 sqq., 149 sq.

153 sq., 157, 173, 178, 209, 217 sq.

264, 359, 363, 406, 522, 614 sq., 617

632 sq., 647 sqq., 651, 655 sqq., 679 sqq.

691

Heatley, 655
Hedin, Sven, 45
Hegar, 148, 321
Van der Heide, 574
Heidenham, 592 sq.
Heil, 69
Heim, 294 sq.

Heinricius, 399, 444, 447. 557
Helme, 561 sq., 564, 582
Helme and Kurdinowski, 562 \

Heine, 155
Henderson, 379, 583
Henking, 672
Henneguy, 151
Hennig, 400

Henriques and Hansen, 283
Hensen, 405, 472
Hepburn and St. John, 277
Herbst, 232, 340
Herdman, 15
Von Herff, 358, 561
Hergesell, 132
HerJitzka, 350
Herokawa, 249
Heron, 659
Herring, 555 sqq.
Herrmann and Neumann, 542
Hertwig. O., 405, 420, 422. 445. 451
Hertwig, O. and R,, 184. 198, 232
Hertwig, R,, 180, 230, 668, sq., 694
Hervieux, 329
Van Herwerden, 55. 56 sq., (35, 84, 90 my.,

132, 570, 584
Hess, 374

Von Heukelom, 493, 496, 498
Hewer, 380 sq.
Hewitt, 126, 238
Heyse, 155
Hickson, 205

Hikmet and Regnault, 321
Hildebrandt, 515, 612
Hilger, 289
Hill, 36, 418 sq., 570
Hill and O'Donoghue, 36, 07, 106 #<•.,

372, 616

Hill and Simpson, 621
Kingston, 57
Hinselmann, 517
Hirschfeld, 321

His, 138, 140, 156, 399, 490, 493
Hitschmann and Adler, 84
Hobday, 361, 722
Hodge, 719 sq.

764

INDEX OF AUTHORS

Hofacker, 683

Hofbauer, 397 sq., 475, 504, 507, 511,

513, 543, 549, 583
Hoffmann, 493
Hoffstrom, 518, 520, 524 sq., 531 sqq.,

546, 549 sq., 551, 554
Hofmeir, 347
Hofmeister, 287, 539, 603
Holdich, 322
Hollard, 451 sq.
Holmes, 254
Holzbach, 377
Home, 176, 647
Honore, 121, 122, 139
Van Hoogenhuyze and Doeschate, 1, 245,

533

Hopkins, F. G., 197
Hopkins and Pinkus, 287
Hoskyns, R. G. and A. D., 386
Hewlett, 12
Hubrecht, 496, 401 sqq., 407, 409 sqq.,

424 sq., 432, 440, 451, 458, 476 sqq.,

485, 488 sq., 490, 497, 508, 510, 518
Hubrecht and Jenkinson, 490
Huffman, 137
Hugounenq, 290 sq., 547
Huish, 176, 648 sq.
Hulton, 518
Hunter, A., 303

Hunter, John, 22, 50, 176, 340, 393 sqq.
Hunter, W., 394
Hunter and Campbell, 506
Hunter, J. and W., 394
Huntley and Wootton, 299
Huramitau and Loeb, L., 582
Hutchinson, Woods, 384
Huth, 224
Hurst, 199
Huxley, 10, 408 sq., 690, 693 sqq.

1

Von Ihering. 679
Imrie, 543

Imrie and Graham, 543
Inge, 660
Ingerslev, 556
Iscovesco, 274, 362
Ishii, 103

Issakowitsch, 670, 681
Isset, 12
Isuka, 10, 128
Itagaki, 577

Iwanoff, 130, 176, 246, 248 aq., 296, 642,
647 sqq.

J

Jacob, 564
Jacobi, 17

Jagerroos, 509, 527, 550
Jagerroos and Ver Eeke, 526
Jankowski, 144
Janosik, 151 sq., 230
Jassinsky, 395

Jobling, Eggstein, and Peterson, 518

Joestens, 302

Johnstone, 493

Jones, 307

Jones, W., 272

Jones and Rouse, 627

Joukowsky, 221

Jeannin, 559

Jenkinson, 181 sqq., 229, 233, 406, 412

sqq., 433, 435 sqq., 441 sq., 468, 470 sq.,

497, 512
Jenner, 22
Jennings, 225

Jennings, Riddle, and Castle, 685
Jentzner and Beuttner, 356

K

Von Kahlden, 80

Kaltenbach, 539

Kallius, 561

Kammerer, 321, 325, 338

Kastschenko, 396 sqq.

Kaupp, 177

Kazzander, 104 sq.

Kehrer, 135, 347, 524. 537, 561 sqq.

Keiffer, 94, 563 sq., 574, 613

Keilin and Nutta], 694

Keilmann, 573

Keller, 98, 373

Kellogg, 325, 664

Kelly, 646, 651 sq., 659, 715

Kennedy, 60

Kerr, 16, 26

King, 217, 578, 627, 669, 679

Kingsbury, 151

Kirkham, 127, 218, 578 sq., 632, 657,

714, 717, 723
Kirkham and Burr, 103
Kirsten, 539
Kite and Chambers, 466
Kite, G. L., 189
Klebs, E., 395
Klebs, G., 7 sq.
Klein, 402, 503
Kleinhaus and Schenk, 371
Klose and Vogt, 380 sq.
Knauer, 348, 350, 361
Knauer and Halban, 361
Knott, 614 sq.
Kohlbrugge, 174, 208
Kohn, 339
Kojima, 391
Kolliker, 114, 138, 140 sq., 152 sq., 159,

248, 263, 300, 395, 593
Kollmann, 493, 517

Kolster, 104, 429, 436 sq., 444, 467, 470 sq
Kolster and Disse, 497
Konigstein, 100
Kopec, 325
Korner, 563

Kossel, 282, 288, 302 sqq., 306, 312
Kossel and Dakin, 305
Kossel and Kutchen, 305

INDEX OF AUTHORS

765

Kossel and Pringle, 304

Kostanecki, 236

Krafft-Ebing, 691

Kraft, 173

Krause, 536

Krause and Cramer, 533, 536

Kraut and Uelsmann, 309

Kronig, 389, 580, 581

Kruieger and Offergeld, 514, 571

Krukenburg, 277, 289, 294

Kundrat and Engelmann, 157, 499, 581

Kuntz, 154, 165

Kupelweiser, 213

Kurdinowski, 561 sq., 564

Kuschakewitsch, 669

Kworostansky, 505

Kyrle, 339

Labhardt, 564

Ladenburg and Abel, 299

Lamers, 550

Lams and Doorme, 127

Landsberg, 531, 551

Landwehr, 300, 603

Lane, 384

Lane-Claypon, 114, 116 sq., 119 sq., 122,

144, 155 sq., 161, 376
Lane-Claypon and Starling, 362, 364,

605, 610 sqq., 615 sq.
Lang, 178
Lange, 558
Langen, 592

Langhans, 395 sq., 496, 503
Langley, 265 sq., 269, 560, 563
Langley and Anderson, 263, 266 sq., 269

sq., 560, 563

Langstein and Neubauer, 537
Lannois and Roy, 323
Lanz, 541

Lataste, 37 sq., 100
Lauder, 596

Lawrence and Riddle, 281
Laycock, 59 sq., 341
Leathes, 507
Lebedeff, 556
Lecaillon, 55, 330 sq.
Ledermann, 432
Lee, 711, 720
Leeney, 569
Leersum, 533
Leeuwenhoek, 159
Lefevre, 236
Lefroy and Howlett, 12
Lehmann, 590, 597
Lemaire, 539
Von Lenhossek, 398
Lenssen, 671

Leopold, 78, 407, 494 sq., 581
Leplat, 168
Leslie, 19
Leuckart, 138
Leusden, 581
Levene, 279, 291

Levene and Mandel, 308

Levick, 29

Leydig, 252

Lichtenstein, 250, 328

Liebermann, 283

Liepmann, 516

Lillie, D. G., 48

Lillie, F. R., 186, 194 sq., 233, 236, 313,

317, 339, 689, 694 aq.
Lillie, R. S., 185
Limon, 350, 386
Linton, 252
Lipes, 76, 80 sq., 83
Lipschiitz, 320, 331 sq., 339, 695, 699
Lipschutz, Ottow, Wagner, and Bormann,

338

Lipschiitz, Wagner, and Tamen, 358
Littlejohn and Pirie, 302
Livingston, 382
Lo Bianco, 12, 14
Lochhead and Cramer, 282, 286, 294,

460, 462 sqq., 522, 538, 545, 557
Lock, 201
Locke, 562

Lode, 169 aq., 246, 296
Loeb, J., 185, 194, 196, 212, 220, 231 sqq.,

285, 313 sq., 316, 318
Loeb, Leo, 38, 103, 107, 122, 136, 144,

151 sqq., 184, 233, 237, 330, 373 sq.,

385, 618, 620 sq., 635, 702 sq.
Loeb, M., 268 aq., 270
Loeb and Bancroft, 315
Loeb and Hesselberg, 372, 620
Loeb and Hunter, 137
Loeb and Kuramitsu, 620
Loeb and Wasteneys, 314
Loewenthal, 157, 378
Loewy, 333, 391
Loewy and Richter, 390 sq.
Loisel, 163, 358

Lloyd- Jones and Hays, 170, 637
Lombroso and Bolaffio, 610
Long and Evans, 37 sq., 103, 130, 149
Longley, 131

Longridge, 579 sq., 582 sqq.
Loosee and Van Slyke, 546
Lott, 170
Loven, 262
Low, 43, 216
Lubarsch, 300
Lucas-Champonniere, 370
Luciani, 133, 243, 254 sq., 715, 723
Lucien, 145

Lucien and Parisot, 380
Lusk, 595, 604
Luthje, 389 sq.
Lydekker, 39 aq., 43, 45, 68

M

Macallum, 311
MacBride, 207, 211
M'Carrison, 384
McClendon, J. J., 184
McClung, 125, 672

;66

INDEX OF AUTHORS

M'Collum, Halpin, and Dreschen, 280,

283

M'Cord, 384
MacEwen, 322
McFadyean, 647, 654
Macgregor, 84
M'llroy, 114

M'Intosh and Masterman, 214
M'lvor, 681
Mackenzie, Sir J., 558
Mackenzie, K.. 621
Mackenzie and Marshall, 130, 203, 361,

389

Mackenzie, Marshall, and Hammond 588
Mac Lean, 21
M'Nee, 542
Maerdervort, 50

Magnus-Levy, 523, 525, 536, 553 sq.
Magnus- Levy and Falk, 391
Majert and Schmidt, 299
Mall, 64, 137
Malthus, 658
Maly, 294
Manassini, 381
Mandl, 80, 561
Mandl and Burager, 377
Mansfield, 280
Mantegazza, 296
Marshall, 32, 39, 55, 92, 103, 130 sq ,

141 sq., 146, 150, 153, 163, 201, 208,

243, 246, 250 sq., 259, 323, 330, 392
Marshall and Crosland, 637, 658
Marshall and Hainan, 34, 84, 92, 98 sq.,

107 373, 617

Marshall and Hammond, 323 sq.
Marshall and Jolly, 32, 48, 50 sqq., 92 sqq.,

96 sqq., 130, 177, 351 sqq., 357, 361, 369,

379, 515, 611

Marshall and Kirkness, 603
Marshall and Peel, 632
Marshall and Runciman, 363
Marshall, Milnes, 74
Martin, 64, 80
Masing, 188
Masius, 456, 458
Massen, 520
Masterman, 15, 213
Matthes, 506

Masquelin and Swaen, 401, 454, 518
Mathews, 129, 233, 236, 294, 306, 311
Matti, 380

Maupas, 221 sq., 667, 671
Maurel, 524, 537
Mayo-Smith, 65 sq.
Mayow, 394

Maximow, 455 sqq., 460, 518
Mead, 230
Meale- Waldo, 54
Meek, 48, 272
Meigs, 597
Medigreceanu, 556
Meisenheimer, 325, 338
Melissenos, 444
Mellanby, E., 288
Mendel, 199

Mendel and Leavenworth, 282

Menu and Mercier, 544

Mercier, 618

Merconitzki, 281

Meredith, 359

Merkel, 163, 243

Merkel and Bonnet, 138, 140, 561, 593

Merletti, 507

Merttens, 499, 503

Messel, L. F., 71, 143

Metchnikoff, 73, 108, 158, 721 sq., 726.

Meyerhof, 0., 185, 188 sq., 195 sqq.

Michaelis, 601

Michel, 525, 546

Miescher, 17, 291, 302 sq., 306 sq., 311 sq.

Millais, 37, 44, 47 sq., 50 sq., 54 sqq.

Miller, 147

Milroy, 291

Minoura, 338, 695

Mingazzini, 145

Minot, 74, 80, 138, 208, 397, 401, 417,

422, 451, 490, 574 sq., 627, 701 sq.>

704 aqq., 709 sq., 719 sq., 725
Miotti, 541
De Mira, 386
Mironow, 609

Mislawsky and Bormann, 268
Misuraca, 243
Mobius, 28
Mohrike, 57, 78, 80
Moenkhaus, M. L., 206, 217
Montgomery, 125 sq., 608
Monticelli, 226
Moore, A., 332, 351, 697
Moore, B., and Parker, 602
Morat, 265
Moreaux, 72
Morgan, 7, 11, 128, 135, 199, 201, 205,.

207, 215 sq,, 229, 231, 321 sq., 334, 344,

641 sq., 661, 663, 667, 671, 673 sq.,

675 sq., 687, 712
Morner, 286, 291
Morris, 348, 360
Morris, M., 206
Mosher, 63
Mott, 310

Mottram and Coope, 541
Muller, 215
Muller, F., 264, 553
Miiller, P., 644, 646
Muller and Masuyama, 289
Muntz, 603
Murlin, 49, 391, 519, 520, 525, 527 sq.,

530, 533 sq., 535 sq., 546, 551 sq., 554
Murlin and Baily, 391
Murlin and Bailey, 533 sq.
Murray, A., 708, 711

N

Nagel, 112, 140, 171, 252S 566, 581
Nasius, 518
Nasse, 556
Nathusius, 42

INDEX OF AUTHORS

767

Nattan-Larrier, 404, 516

Needham, 432

Von Neugebaur, 689

Neubauer and Novack, 540

Neumann, 391

Neumann and Vas, 391

Neumeister, 289, 601

Newbigin, 27

Newcomb, 684, 688

Newman, H. H., 229, 679

Newport, 180

Newsholme and Stephenson, 659

Nicolas, 259

Nielsen, 107

Nikolsky, 262, 266

Niskoubina, 371

Nitabuch, 502

Nolf, 401, 449, 487 sq., 489, 518

Van Noorden, 62, 389, 391, 540, 548

Nussbaum, 136, 246, 337 sq., 671

Ochi, 650

Oddi and Vicarelli, 553

O'Donoghue, 114, 122, 142, 364, 371, 615

Oceanu and Babes, 392, 598

Offergeld, 463

Okkelberg, 664

Oliver, 78, 80, 82, 133, 360, 652

Onuf, 264

Oppermann, 374

Oppler and Rona, 540

Orton, 692

Osborne and Campbell, 287

Osborne and Mendel, 309

Oser and Schlesinger, 57 1

Oshima, 543

Ostwald, Wolfgang, 317 sq.

Ott, 61 sq., 621

Ott and Scott, 250, 272, 621

Oudemans, 325

Overlach, 401

Owen, 28, 39, 55, 243, 258, 395

Painter, 168

Paladino, 140

Pall, 689

Pantin, C. F., 10

Pappenheimer, 380

Parkes, 678

Paterson, 137. 400

Paton, 17, 291, 379 sq., 386, 522

Paton and Cathcart, 604

Paton, Kerr, and Watson, 463

Paton, Watson, B. P., and Kerr, 537

Patten, 28

Patterson, J. T., 183

Payer, 541, 556

Payne, 673

Pearl, 46, 208, 216, 220, 362, 366, 599,

626 sq., 639, 643 sq., 723
Pearl and Boring, 146

Pearl and Parshley, 668, 694

Pearl and Salaman 668

Pearl and Surface, 21, 344, 362, 643 sq..

677, 689

Pearson, 208, 643, 726
Pearson, Lee, and Bramley Moore. 643
Pease, 335
Pelikann, 246
Pembrey, 284
Pepere, 382

Perez, 153, 170, 230, 667
Perry-Coste, 66

Peters, 396, 401, 407, 493 sq., 498, 505
Peters and Leopold, 495 sqq.
Petrunkewitsch, 667
Pezard, 334 sqq., 342 sq., 631, 695, 699
Pfannenstiel, 276
Pfeffer, 224 sq.
Pfister, 610
Pfliiger, 111 sq., 120, 210, 138, 337 sq.

358, 552

Pfliiger and Smith, 210
Philips, 177

Piccolo and Lieben, 273
Pieri, 316
Pinard, 578
Pittard, 323
Pizon, 234

Plimmer, Aders, 283, 288
Plim'mer and Scott, 281
Plonnis, 175, 649
Ploss, 65

Poehl, 247, 299, 328
Pocock, 57, 90. 132, 322
Polaillon, 566
Pool, 385
Popoff, 120
Poncet, 323
Porcher, 602 sqq.
Porges and Novack, 544
Porter, 710
Potthast, 49, 63
Potts, 326, 691 sq.
Pratt, 8
Pregel, 329
Pregl, 290
Prenant, 365
Prevost and Dumas, 177
Preyer, 400
Priestley, 394
Prochownick, 522
Prjewalsky, 38, 45
Przibram.' 129, 229
Punnett, 199, 335, 662, 671, 685
Punnett and Bailey, 335
Pussep, 265

Raciborsky, 43, 133
Ranzi and Tandler, 381
Rasmussen, 114, 163, 331
Rauber, 188, 399, 400
Raudnitz, 595

768

INDEX OF AUTHORS

Ray, 394

Reade, Winwood, 57

Reaumur, 11

Reeves, 336

Reichenstein, 541

Reichert, 472

Reid, 394 sq.

Regaud, 55

Regaud and Dubreuil, 645

Regaud and Policard, 365

Regen, 325

Rehfisch, 243

Rein, 571

Reinke, 300

Reinl, 61 sq.

Rejsek, 100

Remy, 269

Rengger, 50

Repreff, 525

Retterer, 93 sq., 262, 265

Retterer and Voronoff, 372

Retzius, 168

Rhoda, Erdmann, 223

Ribbert, 338, 348, 350, 609

Richardson, 247

Richet, 465

Richmond, Droop, 596

Riddle, 123, 277, 281, 685 sq., 694, 700

Riddle and Anderson, 647

Riddle and Behre, 177

Riddoch, 254

Rieder, 556

Rielander, 506

Riemann, 563, 571

Ries, 363

Rink, 49

Rivers, 254

Robinson, A., 53, 130, 134, 144, 364, 405

sqq., 409, 422, 424, 428 sq., 443 sq., 448,

477, 491, 636
Robinson, J. H., 627
Robertson, 702 sq., 710
Robertson and Ray, 712, 725
Rohrig, 563, 609
Rolleston, 486
Rollinat, 178
Rolph, 665
Romanes, 214
Rommel and Phillips, 643
Rorig, 340
Rose, 604
Rosenbloom, 275
Ross, 12
Roth, 173

Rothschild, Charles, 12
Rouget, 135, 561
Routh, 571 sq., 609
Rubaschkin, 127, 130
Rubinstein, 348
Rubner, 284
Runge, E., 713 sq.
Runge, M., 564
Russell and Gye, 552
Russell and Waoglom, 552
Ryser, 540

Sack, 391

Sadler, 683

Sainmont, 119

St. George, 167

St. Hilaire and Cuvier, 58

Sakamura, T., 206

Salvi, 56

Sand, 327, 332, 347, 351, 696

Sandes, 142 sq., 153, 366 sq., 622

Sanger, 400

Sanson, 667

Sanyal, 57, 59

Sato, 650

Saunders, E. R., 199

Saunders, J. T., 223

Savare, 507

Sauve, 351

Sclater, 59

Scott, 236

Schafer, 22 sq., 72, 112 sq., 115, 120. 144,

147, 160, 163 sq., 167 sq., 310, 577,

589 sqq., 594, 596 sq., 601, 606 53., 621
Schafer and Mackenzie, 621
Schenk, 669
Schil, 616
Schirokauer, 540
Schneidemuhl, 252
Schmidt, Albert, 394, 475
Schmidt, H., 43
Schmidt, J., 17

Von Schmiedelberg, 0., 311, 313
Schmorl, 517
Schochet, 134
Scholter, 583
Schorndorff, 49
Schottlander, 138, 151 sqq.
Schrader, 530, 550
Schreiner, 299
Schroder, 63
Schron, 109, 114
Schulin, 151 sq.

Schultz/350, 426, 566, 669, 684
Schweigger-Seidel, 167
Sedgwick, 6, 10, 68. 178
Seeliger, 205
Seifriz, W., 189
Seiler, J., 671
Seitz, 144, 152 sq.
Selenka, 416, 425, 451, 491 sq.
Seligmann, 323
Sellheim, 77, 79, 81 sqq., 122, 150, 321, 325,

333, 347, 379, 566, 572, 581, 716 sqq.
Semon, 16, 35
Semper, 9, 11, 20, 28
Serres, 562

Serralach and Pares, 249
Sertoli, 264
Seubert, 243
Sexton and Huxley, 694
Sfameni, 62 sq.
Shattock, 347
Shattock and Seligmann, 332 sq., 336,

341, 358, 689
Sharp, 327

769

Sharpey, 432, 493

Shearer, 315

Shearer, C., 184, 192, 197, 661

Shearer, de Morgan, and Fuchs, 211,

Sherren, 254

Sherrington, 266, 269, 359

Shortt, 41, 43

Shull, 668

Von Siebold, 179, 666 sq.

Sigismund, 156 sq.

Sillevis, 531

Simpson, J., 570, 574

Simpson, J. Y., 221

Simpson, S., 22

Simpson and Hill, 621

Simpson and Marshall, 271

Sims, 647

De Sinety, 80, 540

Sixta, 35

Slavjansky, 138

Siemens, 524, 530, 546, 552

Slocum, 559

Slowtzoff, 297

Van Slyke, 518

Smith, F., 569, 710, 721

Smith, B. G., 205

Smith, F., 340, 706

Smith, Geoffrey, 295, 326; 334, 691

Smith, H. P., 130

Smith, Tyler, 574 sq.

Smith arid Schuster, 338

Smyth, 121

Sobotta, 38, 127, 130, 138 sq., 140 sqq.,

144, 151, 468, 470
Sokoloff, 347
Soli, 380
Somerset, 53
Spallanzani, 4, 18, 20 sq., 51, 135, 159,

174 sqq., 211
Von Spee, Graf, 398, 407, 426, 472 sqq.,

493, 497, 500
Spencer, 624 sqq., 628
Spiegelberg, 556, 574, 576
Spiegel berg and Gscheidlen, 557
Spina, 265

Spire and Perrin, 400
Spitzer, 313
Squadrini, 381
Stanley and Kelker, 328
Starkweather, 684
Starling, 364, 387, 516, 574, 614
Steinach, 246, 250, 327 sq., 331, 346, 620,

695 sqq., 700

Steinach and Holzknecht, 331, 347
Steinach and Kammerer, 331, 713
Steinach and Lichtenstern, 328
Steinach and Lipschiitz, 386
Steinhaus, 84, 592 sq., 636
Stendel, 308

Stevens, 11, 670, 672, 676
Stevenson, 61 sq.
Steyn, 106
Stilling, 252, 385
Stilling and Mering, 549
Stockard, C. R., 228

Stockard and Papanicolaou, 38, 102, 134,

208

Stockel, 140

Stockholm and Jena, 168
Stonehenge, 49
Stone, 695
Stolz, 544
Stopes, 64
Stotsenburg, 699
Strahl, 396, 399, 409, 434 sq., 440, 444 sq.,

484, 486, 584
Strahl and Bonnet, 448
Strasburger, 180, 224
Strassman, 80, 177, 358
Strata, 56, 91 sq., 110, 139
Van der Stricht, 117, 121, 123, 128, 131,

142, 144, 148, 151 sq., 487
Sturtevant, 694
Suchetet, 642
Surface, 654
Sutter, 103

Sutton, Bland, 84, 89 sq., 125, 370
Swift, 168
Szabu, 593

Tafani, 130, 434
Tait, Lawson, 157, 558
Tandler, 382

Tandler and Gross, 163, 324, 330, 382
Tandler and Keller, 344, 347, 699
Tangl, 276, 284 sq., 463
Tangl and Farkas, 286
Tarchanoff, 20, 287
Taylor and Husband, 605
Tchermak, 199, 208
Teague and Buxton, 213
Tegetmeier and Sutherland, 614
Tennent and Hogue, 238
Terrier, 549
Tessier, 578

Thiemich, 450, 522, 543
Thierfelder, 601, 603
Thierfelder and Stern, 279
Thompson, D'Arcy, 15
Thompson, H., 303, 537
Thomson, 336
Thomson, A., 73, 121, 127
Thomson, J. A., 159, 207 sq., 661, 685
Thudichum, 274, 279
Thunberg, T., 196, 280, 315 .
Thury, 668

Tichomiroff, 230, 292 sq.
Tiedemann, 253
Tiedje, 339
Tigerstedt, 550
Timofeew, 268
Torelle, 229
Treadwell, 236
Treat, 664
Treviranus, 198
Truzzi, 559
Tschirdewahn, 133

Turner, 54, 395 sq., 403, 409, 421, 427,
432 sq., 440, 490

25

770

INDEX OF AUTHORS

U

Ulesko-Stroganoff, 401, 505
Unna and Golodetz, 313

Names with Van and Von are indexed
under the name following.

Valenciennes and Fremy, 290

Valentin, 112, 263

Vallet, 561

Valtorti, 381

Vater and Noortwyk, 394

Vaughan, 276

Veit, 517, 536, 624

Veit and Scholten, 505, 549, 559

Vernhout, 484 sq.

Vernon, 211

Verworn, 172 sq., 202, 206 sq., 313, 602,

701, 724 sq.
Vicarelli, 62, 544
Vincent, Swale, 329, 386
Virchow, 592, 602, 620
Vies, F., and Dragoin, J., 185
Voit, 540
Volker, 144
Voronoff, 328
De Vries, 199

W

Wade and Watson, B. P., 403, 499
Waldeyer, 110 sqq., 112, 113, 118, 124,

138, 177, 283, 394 sq.
Waldstein and Eckler, 208
Walker, C. E., 333
Walker, G., 248, 251, 300, 329 sq.
Wallace, A. R., 25, 640
Wallace, Cuthbert, 251, 320
Wallace, R., 41, 43, 46 sq., 130, 224,

325, 522, 597, 600, 632, 638, 642, 646,

654

Wallace, W., 15, 145
Wallart, 389
Wallis and Williams, 391
Walsh, 122
Walther, 290 sq.
Warburg, O., 185 sq., 188 sqq., 195, 285,

314

Warner and Edmond, 281
Watson, B. P., 149, 597, 622
Watson, M., 262
Webb, Sidney, 659 sq.
Webster, 74, 133, 137, 158, 402 sq., 495,

498 sq., 502

Weber, 337, 394 sqq., 408, 689
Weichardt and Opitz, 517
Weil, 129
Weininger, 690
Weinland, 293
Weiss, 306, 505
Weismann, 166, 198 sq., 201, 228, 666

670, 721 sq., 724 sq.
Weldon, 432
Wells, 276
Wendeler, 114, 140

Werth, 403

Westermarck, 29, 65, 217

Westphalen, 77, 80, 82, 84

Weymeersch, 585

Wheeler, 667

Whitehead, 330

Whitman, 686

Whitney, 7, 668

Widal, 551

Wiedersheim, 587

Wiener, 400

Wild, 556

Willcock and Hardy, 287

Willey, 15, 423 sq., 476

Williams, Whitridge, 80, 82, 84, 566, 573

576, 578, 581, 583 sq., 597 sq., 624, 651
Williams, J., 78, 80, 582
Williams, W. L., 325, 373 sq.
Willier, 695
Willstatter, 273
Willstatter and Escher, 281
Wilson, E. B., 109, 118, 125 sq., 166, 168,

183, 198, 205, 229, 238, 392, 672 sq.
Wilson, K. M., 532 aq.
Wilson, S. M., 44
Wiltshire, 17. 23, 36, 46, 56, 60
Van Winckel, 551, 558 sq.
Winckelmann, 556

Von Winiwarter, 113, 115, 126, 128, 168
Winiwarter and Sainmont, 128
Winkler, F. N., 396
Winkler, H., 316
Winterhalter, 358
Winterstein and Stickler, 559
Wislocki, 466
Wislocki and Key, 502 sq.
Witschi, 663, 700
Wodsedelak, 168, 678
Wohlgemuth, 289
Wolf, 178, 650
Wolz, 120
Wood, T. B., 203
Wood, W. A., 717
Woodland, 165

Woodman and Hammond, 619
Woodruff, 222 sq.
Woodruff and Britsell, 6
Woodruff and Erdmann, 223
Worthmann, 261
Wright, 21, 341
Wychgel, 549, 559

Yamane, 650
Youatt, 362

Yule, Udny, 380, 659 sq.
Yung, 662 sq.

Zacharjewsky, 523 sq., 530, 540

Zoth, 329

Ziinst and Schumburg, 188

Zuntz, L., 62 sq., 390, 525, 553 sq.

Zweifel, 376

Zweifel and Abel, 377

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