Table Of ContentBIOLOGY OF THE
UTERUS
Second Edition
Edited by
RALPH M. WYNN, M.D.
Professor, Departments of Obstetrics & Gynecology
and Anatomy & Cell Biology
Wayne State University School of Medicine
Detroit, Michigan
and
WILLIAM P. JOLLIE, Ph.D.
Professor and Chairman, Department of Anatomy
Medical College of Virginia
Virginia Commonwealth University
Richmond, Virginia
PLENUM MEDICAL BOOK COMPANY
NEW YORK AND LONDON
Library of Congress Cataloging in Publication Data
Biology of the uterus / edited by Ralph M. Wynn and William P.Jollie. -2nd ed.
p. cm.
Includes bibliographies and index.
ISBN-13: 978-1-4684-5591-5 e-ISBN-13: 978-1-4684-5589-2
DOl: 10.1007/978-1-4684-5589-2
1. Uterus. I. Wynn, RalphM. II. Jollie, WilliamP.
[DNLM: 1. Uterus-anatomy & histology. 2. Uterus-physiology. WP 400 B615]
QP265.B543 1989
599'.016-dc19
DNLMIDLC 89-3540
for Library of Congress CIP
The previous edition of this work was published by Plenum Press in
1977 under the title Biology oj the Uterus. That volume, in turn,
was a revision of Cellular Biology oj the Uterus, published by
Appleton-Century-Crofts in 1967.
© 1989, 1977, 1967 Plenum Publishing Corporation
Softcover reprint of the hardcover 1st edition 1989
233 Spring Street, New York, N.Y. 10013
Plenum Medical Book Company is an imprint of Plenum Publishing Corporation
All rights reserved
No part of this book may be reproduced, stored in a retrieval system, or transmitted
in any form or by any means, electronic, mechanical, photocopying, microfIlming,
recording, or otherwise, without written permission from the Publisher
Contributors
L. L. Anderson Alex F erenczy
Department of Animal Science Departments of Pathology and
Iowa State University Obstetrics and Gynecology
Ames, Iowa 50011 McGill University and
The Sir Mortimer B. Davis Jewish
John D. Aplin General Hospital
Departments of Obstetrics and Montreal, Quebec H3T lE2,
Gynaecology, Biochemistry, and Canada
Molecular Biology
University of Manchester
Manchester M13 OJK, England R. E. Garfield
Departments of Neurosciences and
Christine Bergeron Obstetrics and Gynecology
Departments of Pathology and McMaster University, Health
Obstetrics and Gynecology Sciences
McGiII University and Hamilton, Ontario L8N 3Z5,
The Sir Mortimer B. Davis Jewish Canada
General Hospital
Montreal, Quebec H3T lE2,
Canada Randall L. Given
Department of Anatomy and
w. C. Cole Neurosciences
Division of Cardiovascular Sciences University of Texas Medical
St. Boniface Research Institute Branch
Department of Physiology Galveston, Texas 77550
University of Manitoba
Winnipeg, Manitoba R2H 2AG,
Canada Frank C. Greiss, Jr.
Department of Obstetrics and
Allen C. Enders Gynecology
Department of Human Anatomy Bowman Gray School of Medicine
University of California School of of Wake Forest University
Medicine Winston-Salem, North Carolina
Davis, California 95616 27103
v
VI Gabor Huszar Earl L. Parr
Department of Obstetrics and Department of Anatomy
CONTRIBUTORS
Gynecology School of Medicine
Yale University School of Medicine Southern Illinois University
New Haven, Connecticut 06510 Carbondale, Illinois 62901
c. Y. Kao Margaret B. Parr
Department of Anatomy
Department of Pharmacology
School of Medicine
State University of New York
Southern Illinois University
Downstate Medical Center
Carbondale, Illinois 62901
Brooklyn, New York 11203
Elizabeth M. Ramsey
Wendell W. Leavitt Department of Embryology
Departments of Biochemistry and Carnegie Institution of Washington
Obstetrics and Gynecology Baltimore, Maryland 21210
Texas Tech University Health
Sciences Center James C. Rose
Lubbock, Texas 79430 Departments of Physiology and
Obstetrics and Gynecology
Bowman Gray School of Medicine
Harland W. Mossman
of Wake Forest University
Department of Anatomy
Winston-Salem, North Carolina
University of Wisconsin-Madison
27103
Madison, Wisconsin 53706
Melvyn S. Soloff
Department of Biochemistry
A. I. Musah
Medical College of Ohio
Department of Animal Science
Toledo, Ohio 43699
Iowa State University
Ames, Iowa 50011
Michael P. Walsh
Department of Medical
Ronan O'Rahilly
Biochemistry
Carnegie Laboratories of
University of Calgary
Embryology
Calgary, Alberta T2N 4Nl, Canada
California Primate Research Center
Davis, California 95616
Ralph M. Wynn
Departments of Obstetrics and
Helen A. Padykula Gynecology and Anatomy and
Department of Cell Biology Cell Biology
University of Massachusetts Wayne State University School of
Medical School Medicine
Worcester, Massachusetts 01655 Detroit, Michigan 48201
Preface
Almost a quarter of a century has elapsed since Cellular Biology of the Uterus, the predecessor
of the present volume, was planned. During that period, especially in the decade since the
publication of the last edition of Biology oft he Uterus, new information in the field has been so
voluminous as to require major revisions of most of the chapters, the addition of several new
chapters, and the collaboration of a second editor to facilitate the selection of appropriate
experts as authors. As in prior editions, a balance has been struck between classical biology
and modem biochemistry and biophysics. The inclusion of basic histological and embryo
logical information provides a necessary, though often lacking, background for the protein
chemist and molecular biologist and a bridge between the cell biologist and clinician. Thus,
major practical problems in human reproduction, such as the genesis of endometrial carcinoma
and the cause of the initiation of labor, may be approached on a firm scientific footing.
The current edition deals primarily with the biology of the uterus itself (comparative and
human) rather than placentation or pregnancy and thus is a synthesis of data derived from
many techniques, both conventional and modem. As it is clearly beyond the competence of
anyone scientist to prepare such a text on the basis of personal knowledge and experience, the
aid of 22 distinguished scientists was enlisted. All of these authors, acknowledged experts in
their respective fields, agreed to extensive revisions of their chapters in the previous edition or
preparation of entirely new contributions.
A scholarly history of uterine biology has been retained to illustrate the evolution of
studies from superstition to speculation to science. The chapters on comparative anatomy and
embryology of the human genitourinary tract have been revised by their original authors. It is
noteworthy that Dr. Mossman's chapter was prepared on the occasion of that distinguished
scientist's 90th birthday. An extensively revised chapter on vascular anatomy and a new
chapter on vascular physiology of the uterus, emphasizing the nonpregnant condition, precede
the final 12 chapters, which stress cell biology. Comparative embryology of the miillerian
derivatives provides the basis for predicting and analyzing the cellular response of the uterus to
hormones. The chapters on vascular anatomy and physiology illustrate the dominant role of
blood vessels in critical uterine functions such as menstruation and pregnancy, the effects on
uterine blood flow of hormones, oxygenation, vasoactive amines, and prostaglandins, and the
changes in uterine arteries as they relate to preeclampsia and retardation of intrauterine growth.
Two entirely new complementary chapters on biochemistry and cell biology of the
endometrium bridge the gap between morphology and biochemistry and illustrate the crucial
role of receptors in endocrine regulation of uterine activity. The cytoskeletal proteins, the
biochemistry of the cellular surface, the extracellular matrix, and the secretory components of
the endometrium are discussed as they relate to implantation and associated phenomena. The
interrelations of the actions of steroid and peptide hormones, receptor status, synthesis of
VB
nucleic acids and proteins, and regulation of gene expression are detailed in one of the new
Vlll
pivotal chapters of this edition. The chapter on delayed implantation has been revised and
PREFACE extended to include a discussion of the uterus during early implantation, with detailed data
derived from studies of marsupials and several orders of eutherian mammals. Delayed implan
tation strikingly illustrates the mediation of the developmental rate of one organism (the
unimplanted blastocyst) by the internal environment (the uterus) of another. A new chapter on
the implantation reaction discusses experimental techniques and hormonal sensitization of the
endometrium for implantation. Contributions of electron microscopy to the understanding of
several fundamental problems in reproductive biology are well documented. In particular, the
role of prostaglandins in the initiation of decidualization and the importance of apoptosis as the
mode of cellular death in uterine epithelium are discussed. A short but stimulating chapter on
the role of stem cells in the regeneration of the primate uterus presents work currently in
progress in the author's laboratory.
The chapter on the human endometrium, which encompasses histology and scanning and
transmission electron microscopy, has been expanded to include a detailed discussion of the
endometrial vascular changes in normal and hypertensive pregnancies. The information de
rived from transmission electron microscopy deals with basic problems, such as the origin and
significance of the nucleolar channel system and the functions of the decidua, and clinical
applications, such as the morphological effects of contraceptives and the cause of menstrua
tion. The morphological correlates of preeclampsia and other abnormal gestational states are
illustrated. The chapter on pathology of the endometrium advances the thesis that hyperplasia
and neoplasia may have fundamentally different causes in this tissue.
Two of the three chapters dealing with biochemistry, electrophysiology, and ultrastruc
ture of the myometrium are entirely new. The need for collaboration between the electron
microscopist and the biochemist in elucidating the contractile mechanism of the myometrium
is amply demonstrated. Although much more is known about skeletal muscle than about
smooth muscle, the major data concerning the provision of energy and the proteins of the
contractile mechanisms of mammalian myometrium are presented. The organelles of smooth
muscle are discussed in detail, with particular emphasis placed on the role of gap junctions in
myometrial contractility. The chapter on electrophysiology of the myometrium focuses on
patterns of ionic distribution and resting potential and their modifications by hormonal and
gestational influences. Current experiments dealing with single-cell myometrial preparations
are discussed authoritatively in appropriate detail.
The last two chapters, the second of which is entirely new, discuss the uterine regulation
of ovarian function and the endocrine control of parturition. Effects of hysterectomy on
ovarian function and luteolytic action of the uterus are analyzed. The effects of ovarian and
adrenal steroids, prostaglandins, and oxytocin on uterine activity in several species, including
man, are discussed. Although the emphasis of the volume as a whole is not on pregnancy, the
final chapter is obviously relevant to experimental biologists, endocrinologists, and
obstetricians.
Even though each of the chapters is a self-contained unit, which provides a critical review
and a comprehensive list of references for the graduate student, the intended interdisciplinary
orientation is best achieved by reading the chapters in the order in which they appear. The
volume is designed to serve as an introduction for the academic clinician to the scientific
foundations of reproductive biology, as a suggestion to the basic scientist of significant
applications of uterine biology, and as a bridge between morphologists and pathologists on the
one hand and biochemists and physiologists on the other. If new or enhanced interdisciplinary
collaboration is stimulated by this volume, the efforts of the authors and the editors will be
rewarded.
Detroit, Michigan Ralph M. Wynn
Richmond, Virginia William P. Jollie
Contents
1 History 1
ELIZABETH M. RAMSEY
1. Greece. . . . . . . . . . . .. . . .. . . . . .. . . .. .. . .. .. . . . .. . . . . . . . . . . . . . . . 1
2. Alexandria. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
3. Rome....................................................... 4
4. The "Dark Ages" ............................................ 4
5. Renaissance. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
6. Seventeenth to Early Twentieth Centuries . . . . . . . . . . . . . . . . . . . . . . 8
7. Contemporary.. .. ............................ .......... ..... 13
8. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2 Comparative Anatomy 19
HARLAND W. MOSSMAN
1. Types of Uteri .............................................. 22
2. Distribution and Probable Evolution of Uterine Types .......... 23
3. Correlations of Uterine Types with Other Biological
Features .................................................... 27
4. Miscellaneous Aspects of the Comparative Morphology
of the Uterus. . . . . . . . . . . . . . . . . . . .. . . . . . . .. . . . . . . . . . . . . . . . . . . . 29
5. Summary and Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
6. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
7. Bibliography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
3 Prenatal Human Development 35
RONAN O'RAHILLY
1. Urinary Preliminaries 35
IX
x 2. The Para mesonephric Ducts............ ........ ... ..... ...... 37
3. The Vaginal Controversy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
CONTENTS 4. The Fetal Uterus ............................................ 49
5. The Second Half of Prenatal Life ............................. 50
6. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53
4 Vascular Anatomy 57
ELIZABETH M. RAMSEY
1. Basic Aspects of Architecture and Physiology of Uterine Arteries 58
1.1. Nonpregnant.......................................... 58
1.2. Pregnant. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
2. Interaction of Trophoblast and Decidua ....................... 62
3. Contemporary Studies ....................................... 65
4. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66
5 Vascular Physiology of the Nonpregnant
Uterus 69
FRANK C. GREISS, JR., AND JAMES C. ROSE
1. Fundamental Characteristics of the Uterine Vasculature ........ . 70
1.1. The Pressure-Flow Relationship ....................... . 70
1.2. Autonomic Influences ................................. . 70
1.3. Effects of Myometrial Contractions ..................... . 73
1.4. Endocrine Regulation ................................. . 74
2. Uterine Blood Flow during the Ovarian Cycle ................. . 77
2.1. Temporal Changes .................................... . 77
2.2. Hormonal and Other Correlates ........................ . 78
3. Mediators of Estrogen-Induced Vasodilatation ................. . 79
4. Responses of the Nonplacental Uterine Vasculature during
Pregnancy ................................................. . 81
5. Conclusion ................................................. . 84
6. References 84
6 Cellular Biochemistry of the Endometrium 89
JOHN D. APLIN
1. Methodological Comments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
2. Intracellular Constituents ........ . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91
2.1. Cytoskeletal Proteins ................................... 91
2.2. Oncogene Products .................................... 95
2.3. The 24k Protein ....................................... 96
3. Cell Surface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
3.1. Cell Polarity ........................................... 97
3.2. Cell Location .......................................... 97 Xl
3.3. Hormone-Dependent Alterations........................ 98
CONTENTS
3.4. Preparation for Implantation ........................... 100
4. Extracellular Matrix . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
4.1. Interstitial Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100
4.2. Basal Laminal Components ............................. 106
4.3. Functional Significance of Matrix Reorganization ......... 108
5. Secretory Components ....................................... 109
5.1. Uteroglobin. .. . ... .. .. ..... .. . .. .. .. . . . . .. .... . ... . . .. 109
5.2. Iron-Binding Secretory Products ........................ 110
5.3. Prolactin. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 111
5.4. Diamine Oxidase. .. . . . . . . .. .. . . . . .. . . ... . .. . . . . . . . . . . .. 111
5.5. <x2-PEG. . . . . . . . ... . .. ... .. . .. . . . . . . .. . . . .. . . .. . . . .. . .. 112
5.6. <XcPEG. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 113
5.7. High-Molecular-Weight Components .................... 114
5.8. Other Glycoproteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 117
6. Concluding Remarks ......................................... 118
7. References. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 119
7 Cell Biology of the Endometrium 131
WENDELL W. LEAVITT
1. Mechanism of Hormone Action ............................... 134
1.1. General Mechanism of Hormone Action ................. 134
1.2. Polypeptide Hormones ................................. 134
1.3. Steroid Hormones ..................... ,............... 135
1.4. Estrogen Marker Proteins .............. ;. . . . . . .. . . . . . . .. 137
1.5. Progesterone Marker Proteins. . . . . . .. . . .. . . .. . . . . . . . . . .. 137
2. Steroid Receptors ............................................ 146
2.1. Receptor Distribution .................................. 146
2.2. Receptor Assays ....................................... 147
2.3. Nuclear Acceptor Sites ................................. 149
2.4. Estrogen-Progestin Interactions............ .... .... ..... 150
2.5. Hamster Estrous Cycle .................... ;............ 152
2.6. Pregnancy.. . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . .. 154
2.7. Density-Shift Studies ................................... 154
2.8. A Unifying Concept. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 159
3. References. . . . . . . . . . . . . . . . . . . . .. . . . . . . . . . . . . . . . . . . . . . . . . . . .. 162
8 The Endometrium of Delayed and Early
Implantation 175
RANDALL L. GIVEN AND ALLEN C. ENDERS
1. Marsupials. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. 176
2. Roe Deer ................................................... 179
