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T.G. Cooper
The Epididymis, Sperm Maturation and Fertilisation
With 8 Figures and 21 Tables
Springer-Verlag Berlin Heidelberg New York London Paris Tokyo
Dr. TREVOR G. COOPER
Max-Planck-Gesellschaft zur F6rderung der Wissenschaften e. V. Klinische Forschungsgruppe fUr Reproduktionsmedizin an der Frauenklinik der UniversiUit Munster Steinfurter StraBe 107, 4400 Munster, FRG
The cover photograph is of a decapsulated, partially unravelled length of tubule from the rat epididymis from which spermatozoa have been removed through the cannulae inserted into each end. For the photograph it has been filled with air, but when continuously perfused with physiological solutions and immersed in an organ bath it can provide information on the permeability of the epididymal epithelium.
ISBN -13: 978-3-642-71473-3 e-ISBN -13: 978-3-642-71471-9 DOl: 10.1007/978-3-642-71471-9
Library of Congress Cataloging-in-Publication Data. Cooper, T. G. (Trevor G.), 1949-The epididymis, sperm maturation, and fertilisation. Includes bibliographies and index. 1. Epididymis. 2. Spermatozoa. 3. Fertilization. I. Title. [DNLM: 1. Epididymis. 2. Fertilization. 3. Sperm Maturation. WJ 800 C778el QP255.C66 1986 612'.61 86-20354 ISBN-13:978-3-642-71473-3 (U.S.)
This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 ofthe German Copyright Law where copies are made for other than private use, a fee is payable to "Verwertungsgesellschaft Wort", Munich.
© Springer-Verlag Berlin Heidelberg 1986 Softcover reprint of the hardcover 1st edition 1986
The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use.
Product Liability: The publishers can give no guarentee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature.
2127/3130-543210
This work is dedicated to Marie-Claire Orgebin-Crist, who first showed me the way to epididymal enlightenment, and my Chinese scientist colleagues to whom I hope I have done the same.
Preface
The epididymis has great significance in the reproductive biology of the male and it is gaining recognition as an organ worthy of study in its own right - where the secretory and absorptive activities of one tissue (the epithelium) profoundly modify the function of another (the spermatozoon). Apart from cases of epididymal agenesis or physical blockage, however, it is not yet known to what extent malfunctions of the epididymis contribute to "unexplained" male infertility, but its importance as a target for antifertility agents in the male is now widely appreciated.
This monograph evolved from two lectures on epididymal function given at the National Research Institute for Family Planning, Beijing and the Sichuan Provincial Family Planning Research Institute, Chengdu, China in 1983. In order to stress for this audience the central importance of the epididymis in fertilisation, and so highlight its potential for attack by antifertility agents, the talks attempted to put the epididymis in reproductive perspective by stressing the functional development of the sperm cells during their sojourn in the epididymis, rather than merely listing the changes observed in them. This required a discussion of the mechanisms of fertilisation, necessarily obtained from studies on mature spermatozoa, and the contrast between the success of these sperm and the limitations suffered by immature sperm in performing certain steps in fertilisation was used to reveal which functions of the developing sperm were influenced by the epididymis. While more is becoming known about epididymal secretions, especially specific proteins, there is as yet no full appreciation of the significance of these secretory products for sperm function, although in the last five years headway has been made by the recognition of specific secretory products of the epididymis that initiate and modulate sperm motility and influence sperm-egg binding.
Even now the most frequently cited review of epididymal function is one published in 1975 (Hamilton and Greep, 1975). Since then, reviews of epididymal function have ranged from short synopses (Hacker, 1984) or slightly longer works (Turner, 1979; Hinton, 1980; Orgebin-Crist, 1981, 1985; Orgebin-Crist and Olson, 1984) to those devoted to only one aspect of maturation (Dacheux and Paquignon, 1981). Longer tracts (Orgebin-Crist and Hochereau-de Reviers, 1980; Orgebin-Crist et aI., 1981) have appeared in books nominally about testicular function and the one book devoted to epididymal function (Bollack and Clavert, 1981) was not comprehensive in its coverage.
VIII Preface
Because of this, the wider aspects of the subject covered in these lectures required access to numerous journals, many of which were unavailable to the Chinese Institutes.
This work then, is an attempt to bring together the information relevant to the approach cited above, including a tabulation of the composition of luminal fluid in various regions of the epididymis, the "milieu exterior" of utmost importance to the maturing spermatozoa. The topics covered are necessarily many and overviews of the mechanisms under study at present have been included at the expense of detailed criticism of methodology. Despite these shortcomings, it is hoped that the information contained therein will prove useful as a backdrop to, and provide a framework from which to see, future studies on the epididymis.
The impetus to originate these ideas was the opportunity to present lectures in China, and for this I am grateful to Dr. F. T. G. WEBB of the WHO Special Programme of Research in Human Reproduction, Geneva and Dr. CHANG CHAr-FEN, at that time the Director of the National Research Institute for Family Planning, Beijing. I was encouraged by my Chinese colleagues there and Professor E. NIESCHLAG here to expand these thoughts and I thank them and Springer Verlag for providing the opportunity to publish them. Material was gathered during the tenure of a Wellcome Trust Senior Fellowship and a Project Grant from the Medical Research Council at Bristol University, England, where the resources of the University library proved invaluable. I am indebted to Dr. M. REA for introducing me so painlessly to the benefits of the computer, without which the work would not have been completed. Finally, I am most grateful to my wife for her gentle encouragement and patient toleration at times of exasperation experienced during the compilation of the work.
T. G. COOPER
References
Bollack C and Clavert A (1981) (Eds) Epididymis and Fertility: Biology and Pathology. Progress in Reproductive Biology, Volume 8
Dacheux JL and Paquignon M (1981) Physiologie epididymaire et maturation des spermatozoides. Actualites gynecologiques Ser 12, Masson Press, Paris. pp201-213
Hacker PJ (1984) Un aper9u sur les connaissances actuelles de la physiologie de l'epididyme. J Urol (Paris) 90:57-62
Hamilton DW and Greep RO (1975) (Eds) Male Reproductive System, Volume 5, Section VII, Endocrinology, Handbook of Physiology. American Physiological Society, Washington DC
References IX
Hinton BT (1980) The epididymal microenvironment. A site of attack for a male contraceptive? Invest UroI18:1-10
Orgebin-Crist MC (1981) Epididymal physiology and sperm maturation. In: Epididymis and Fertility: Biology and Pathology. Eds C Bollack and A Clavert, S Karger, Basel. pp 80-89
Orgebin-Crist MC (1985) Epididymal maturation of spermatozoa. In: Recent Progress in Cellular Endocrinology of the Testis. Eds JM Saez, MG Forest, A Dazord and J Bertrand, INSERM, Paris. pp 85-90
Orgebin-Crist MC and Hochereau-de Reviers DE (1980) Sperm formation and maturation - role of testicular and epididymal somatic cells. In: 9th Int Congr Anim Reprod and AI, Madrid, Spain. Editorial Garsi, Madrid. pp 59-82
Orgebin-Crist MC and Olson GE (1984) Epididymal Sperm Maturation. In: The Male in Farm Animal Reproduction. Ed M Courot, Martinus-Nijhoff, Boston. pp 80-102
Orgebin-Crist MC, Olson GE and Danzo BJ (1981) Factors influencing maturation of spermatozoa in the epididymis. In: Intragonadal Regulators of Reproduction. Eds P Franchimont and CP Channing. Academic Press, New York. pp 393-417
Turner TT (1979) On the epididymis and its function. Invest UroI16:311-321
Contents
Part I. Maturation of Spermatozoa in the Epididymis. . . 1
1. Acquisition in the Epididymis of Sperm Fertilising Ability . . . . . . . . . . . . . . . . . . . 1
2. Involvement of the Epididymis in the Development of Sperm Fertilising Ability . . . . . . . . . . 2
3. The Nature of the Androgen-Dependent Epididymal Secretions Involved. . . . . . . . . . . . . . 4
4. Response of Immature Spermatozoa to Epididymal Secretions. . . . . 4
5. Scope of this Review 4 6. Summary . 5 7. References . . . . 5
Part II. Fertilisation 9
A. Sperm Motility 9 1. The Need for Flagellar Activity of Sperm for Them
to Reach the Egg ............. 9 2. The Ability of Immature Spermatozoa to Reach
the Site of Fertilisation . . . . . . . . . . . 10 3. Development in the Epididymis of Sperm Motility
In-Vitro .................. 11 4. The Nature of the Reduced Motility of Immature
Spermatozoa . . . . . . . . . . . . . . .. 12 5. Involvement of the Epididymis in the Maturation
of Motility . . . . . . . . . . . . . . . . 23 6. Induction of Motility in Immature Spermatozoa
In-Vitro ............... 24 7. Relationship of Induced Forward Motility
to Fertilising Ability 27 8. Summary . 27 9. References . . . . 27
B. Capacitation .... 42 1. Detection of Capacitation 42 2. Changes in the Sperm Surface During Capacitation 43 3. Mechanisms of Capacitation. . . . . . . . .. 43
XII Contents
4. Consequences for Membrane Fluidity . 45 5. Action of Decapacitation Factors 45 6. Maintenance of Motility . . . . . . 46 7. Requirements of Capacitation . . . . 46 8. Development in the Epididymis of the Ability
of Spermatozoa to be Capacitated . . . . . 46 9. Involvement of the Epididymis in Permitting
Capacitation 47 10. Summary . . . . . . . . . . . . . . . . 49 11. References . . . . . . . . . .. . . . . 49
C. Consequences of Capacitation. I. Sperm-Egg Binding 56 1. Sperm-Egg Binding. . . . . . . . . 56 2. Relationship to Capacitation .... 56 3. Relationship to the Acrosome Reaction 56 4. Mechanisms of Binding . . . . . . . 57 5. Development in the Epididymis of the Ability
of Sperm to Bind to Eggs . . . . . . . . . 58 6. Involvement of the Epididymis in the Development
of the Sperm Surface 59 7. Summary . . . . . . . . . . . . . . . . .. 62 8. References . . . . . . . . . . . . . . . .. 62
D. Consequences of Capacitation. II. The Acrosome Reaction 67 1. The Acrosome Reaction ....... 67 2. Mechanism of the Acrosome Reaction 67 3. Requirements for the Acrosome Reaction 68 4. Stimulus to the Acrosome Reaction. . . 72 5. Relationship to Capacitation ..... 72 6. Relationship to Hyperactivated Motility . 73 7. Relationship to Fertilisation . . . . . . 73 8. Site of the Acrosome Reaction . . . . . 73 9. Consequences of the Acrosome Reaction 74
10. Development in the Epididymis of the Ability of Spermatozoa to Undergo the Acrosome Reaction 76
11. Involvement of the Epididymis in Permitting the Acrosome Reaction 78
12. Summary . . . . . . . . . . . . . . . . 79 13. References . . . . . . . . . . . . . . . 79
E. Consequences of Capacitation. III. Hyperactivation 89 1. Hyperactivation . . . . . . . . . . . 89 2. Requirements of Hyperactivated Motility 90 3. Mechanisms of Hyperactivated Motility 91 4. Stimulus to Hyperactivated Motility 92 5. Relationship to Capacitation .... 92 6. Relationship to the Acrosome Reaction 92 7. Relationship to Fertilisation . . . . . 93
Contents XIII
8. Site of Hyperactivated Motility ...... 93 9. Consequences of Hyperactivated Motility . . 94
10. Development in the Epididymis of the Ability of Sperm to Display Hyperactivated Motility 95
11. Involvement of the Epididymis in Permitting Hyperactivation 96
12. Summary . . 96 13. References 96
F. Sperm-Egg Fusion . 101 1. Binding to the Vitellus 101 2. Fusion with the Vitellus. 101 3. Relationship to Capacitation 102 4. Relationship to the Acrosome Reaction 102 5. Relationship to Sperm Motility 102 6. Regions of the Sperm Head Involved in Fusion 102 7. Basis of Fusion . . . . . . . . . . . . . 104 8. Development in the Epididymis of the Ability
of Sperm to Fuse with Eggs . . . . . . . . 104 9. Involvement of the Epididymis in Permitting
Sperm-Egg Fusion 105 10. Summary . . . 105 11. References 105
G. Post-Fusion Events. . 108 1. Activation of the Eggs 108 2. Decondensation of Sperm Chromatin 109 3. Formation of the Male Pronucleus . 110 4. Chromosome Condensation . . . . 110 5. Development in the Epididymis of the Ability
of Sperm to Interact with the Vitellus . . . 110 6. Involvement of the Epididymis in Permitting
Post-Fusion Events. 111 7. Summary . 112 8. References . . . . 112
Part III. Function of the Epididymis and Its Secretory Products. . . 117
A. Epididymal Structure and Function 117 1. Introduction. . . . 117 2. Epididymal Structure 118 3. Blood Supply . . 119 4. Lymphatics . . . 120 5. Methods of Study 120 6. Epithelial Cells 121
XIV Contents
7. Testicular Control of Epididymal Function 123 8. Permeability of the Epididymal Epithelium 124 9. Resorptive Activity of the Epididymis. 127
10. Secretory Activity of the Epididymis 128 11. Summary . 128 12. References . . . . . . . . . . 128
B. Secretion of Steroids by the Epididymis 139 1. Steroids in Epididymal Tissue . . 139 2. Origin of Epididymal Steroids . . 140 3. Testicular Control of Androgenic Function
in the Epididymis . . . . . . . . . . 142 4. Endocrine Role of the Epididymis . . . 146 5. Role of Steroids in Epididymal Function 147 6. Interactions of Steroids with Spermatozoa 149 7. Role of Steroids in Spermatozoal Function 150 8. Summary . 152 9. References . . . . . . . . . . . . . . 152
C. Resorption and Secretion of Ions by the Epididymis 163 1. Luminal Contents . . . . . . . 163 2. Transporting Activities . . . . . . . . . 163 3. Control of Transporting Activities . . . . 164 4. Role of Monovalent and Divalent Cations. 165 5. Interactions of Ions with Maturing Spermatozoa 166 6. ATPase Activity in Spermatozoa 167 7. Polycations 167 8. Summary . 168 9. References 169
D. Epididymal Secretion of Glycerophosphocholine (GPC) 174 1. Concentration in Epididymal Tissue 174 2. Origin of Epididymal GPC . . . . . 174 3. Androgen Dependence . . . . . . . 176 4. Role of GPC in Epididymal Function . 176 5. Summary . 177 6. References . . . . . . . . . . . . 177
E. Epididymal Secretion of Carnitine 180 1. Concentration in Epididymal Tissue 180 2. Origin of Epididymal Camitine 180 3. Androgen Dependence . . . . . . 181 4. Interaction of Camitine with Maturing Spermatozoa 182 5. Roles of Camitine in Epididymal Function 182 6. Summary . 186 7. References . . . . . . . . . . . . . . 186
Contents XV
F. Epididymal Secretion of myo-Inositol 191 1. Concentration in Epididymal Tissue 191 2. Origin of Epididymal Inositol 192 3. Androgen Dependence . . . . . . 193 4. Metabolism ofInositol . . . . . . 194 5. Interaction of Inositol with Maturing Spermatozoa 194 6. Role of Inositol in Epididymal Function 195 7. Summary . 196 8. References . . . . . . . . . . . . . 196
G. Epididymal Secretion and Resorption of Proteins 200 1. Luminal Proteins. . . . . . . . . . . . 200 2. Origin of Epididymal Proteins . . . . . . 200 3. Protein Synthesis and Precursors in the Epididymis 202 4. Protein Secretion in the Epididymis. . . . . 204 5. Androgen Dependence . . . . . . . . . . 205 6. Control of Protein Synthesis by Luminal Fluid 206 7. Site of Synthesis of Specific Proteins . . . . 207 8. Evidence for Interactions of Luminal Proteins
with Spermatozoa . . . . . . . . . . . . 207 9. Binding of Proteins to Maturing Spermatozoa 209
10. The Nature of the Interaction . . . . . 211 11. Site of Binding ........... 212 12. Role of Proteins in Epididymal Function 212 13. Peptides .............. 215 14. Resorption of Proteins by the Epididymis 216 15. Summary . 217 16. References . . . . . . . . . . . . . 217
PartlV. Conclusions . . . . . . . . . . . . . . . .. 231
1. The Importance of the Epididymis in Male Fertility. 231 2. Summary . . . . . . . . . . . . . . . . . .. 232
Appendix I (fables 1-21) 233
Appendix II (Figures 1-8) 269
Subject Index 277
