HUMAN FETAL ENDOCRINES

DEVELOPMENTS IN OBSTETRICS AND GYNECOLOGY

VOLUME 1

1. J. E. Jirasek, Human fetal endocrines, 1980. ISBN 90-247-2325-6. 2. P. M. Motta, E. S. E. Hafez, eds., Biology ofthe ovary, 1980. ISBN 90-247-2316-7. 3. J. Horsky, J. Presl, eds., Ovarian function and its disorders, 1980. ISBN

90-247-2326-4. 4. D. W. Richardson, D. Joyce, E. M. Symonds, eds., Frozen human semen, 1980.

ISBN 90-247-2370-1. 5. E. S. E. Hafez, W. A. A. van Os, eds., Medicated intrauterine devices, 1980.

ISBN 90-247-2371-X.

Series ISBN 90-247-2334-5 .

HUlUan Fetal Endocrines

JAN E. JIRÄSEK, M. D., D. Sc.

Institute für the Care üf Müther and Child,

Prague

1980

SPRINGER-SCIENCE+BUSINESS MEDIA, B.Y.

Distributors: jor the United States and Canada Kluwer Boston, Inc. 190 Old Derby Street Ringham, l\IA 02043 USA

jor all other' eountries Kluwer Academic PublisherR Group Distribution Center P.O. Box 322 3300 AR Dordrecht The Netherlands

jor Hungary, Albania, Bulgaria, China, Cuba, Czeehoslovakia, German Demoeratie Republie, Demoeratie People' s Republie of Korea, Mongolia, Poland, Rumania, Soviet Union, Demoeratie Republie oj Vietnam, and Yugoslavia

AVICENU)I, Czechoslovak Medical Press, Pragup

ISBN 978-94-009-8194-2 ISBN 978-94-009-8192-8 (eBook) DOI 10.1007/978-94-009-8192-8

This book is published with an arrangement of Avieenum, Czechoslovak Medical Press, Prague

All rights reserved. No part of this publieation may be reproduced, stored in a retrieval system, or transmitted in any form by any means, mechanical, photocopying, recording, or otherwise, without the the prior written permission of the publisher, Springer-Science+Business Media, B. V.

Copyright © by Springer Science+Business Media Dordrecht 1980 Ursprünglich erschienen bei Martinus Nijhoff, The Hague, Netherlands 1980 Softcover reprint of the hardcover 1st edition 1980

To my wife Vera

in appreciation of all her support.

CONTENTS

CHAPTER 1 .. General ideas. Hormones ... Action of hormones Feed·back mechanisms

CHAPTER 2 .... Basic· Survey of Human Prenatal Development. Embryonal period . . . . . . . .

Unicellular stage (48 hours) ... Blastomeric stage (days 3 and 4) Blastodermic stage (days 4 - 6) Bilaminar embryo (days 6-14) . Trilaminar embryo (days 15-20) Early somite embryos (days 20-30) Stage oflimb development (days 28-53) Late embryonal stage (days 52-60)

Fetal period (weeks 9-26) .. Perinatal period (weeks 27 -40)

CHAPTER 3 ....... . The placenta ...... . Trophoblast of the blastocyst and trophoblastic shell . Decidua Chorion .....

Early chorion . . The late chorion .

Structure of the placenta Placental trophoblast Cytotropho blast . . . Syncytiotrophoblast . Fibrinoid ..... .

Uteroplacental circulation The placental membranes .

Extraplacental chorion . Extraplacental amnion .

Survey of placental functions Endocrinology of the placenta .

Human chorionic gonadotropin (hCG) Human chorionic somatomammotropin (hCS) Human chorionic thyrotropin (hCT) . . . . Chorionic TRH . . . . . . . . . . . . . Human chorionic corticotropin (hCC). . . .

Steroid hormone synthesis by the trophoblast (placenta) Trophoblastic (placental) progesterone.forming compartment Placental 17 p.estradiol.forming compartment . . . . . . . Placental estriol·forming compartment . . . . . . . . . .

Compartmentalization of steroid production within the fetoplacental unit The fetoplacental unit . . . . . . . Phylogenesis of the placenta Pathology of the chorion and placenta

Avascular chorionic villi . . . . .

VII

1 I 4 5

7 7 7 7 7 7 9

12 16 16 18 18 18

26 26 26 28 28 28 30 32 35 35 36 38 38 39 39 39 40 41 41 45 46 46 47 47 47 48 48 52 52 54 56 56

Choriodeciduitis and chorioamnitis . 58 Primary intervillous thrombosis 59 Chorionic stromal fibrosis . . . . 59 Placental infarcts . . . . . . . 59 Placentitis secondary to infections 60 Listerial placentitis 60 Tuberculous placentitis . 60 Syphilitic placentitis . . 60 Toxoplasmic placentitis. 61 Placental pathology in metabolic diseases 61 Placental tumors 61

Placental chorioangioma . . . . . . . 61 Trophoblastic disease ........ 62 Trophoblastic infiltration and deportation 67

Placental steroid sulphatase deficiency . 67 Placental insufficiency . . . . . . . . 67

The fetus, fetal membranes and parturition. 67

CHAPTER 4 . . . 69 Fetal adrenal. . 69 The adrenal cortex . 69 The adrenal medulla 73 Prenatal growth of the adrenal 74 Accessory adrenals. . . . . . 75 Phylogenesis . . . . . . . . 75 .steroidogenesis in the fetal adrenal 75 The effects of aldosterone . . . . . 77 The effect of glucocorticoids. . . . 79 Compartmentation of the steroid synthesis in the adrenal 79 Adrenal androgens and congenital adrenal hyperplasia 80 Clinical forms of congenital adrenal hyperplasia . . . . 80 Congenital adrenal hypoplasia. . . . . . . . . . . . 81 Hereditary adrenocortical atrophy and diffuse cerebral sclerosis 81 Hormones of the adrenal medulla 81 Congenital neuroblastoma 82

CHAPTER 5 . . . . . . 83 Testes, Ovaries and the Genital System 83 Primordial germ cells ....... 83 The indifferent gonad (genital ridge) 84 Development of the testis 86 Embryonal testis. . . . . . . 86 Fetal testis . . . . . . . . . 89 Development of the ovary 91 Early fetal ovary 92 Late fetal ovary. . . . . . . 95 Perinatal ovary . . . . . . . 96 Prenatal and perinatal degeneration of the oogonia and oocytes and atresia of follicles 98 Development of the genital ducts 100 Mesonephric (Wolffian) duct 100 Paramesonephric (Mullerian) duct . 101 Urogenital sinus . . . . . . . . . 101 Masculinization of the genital ducts 102 Regression of the paramesonephric duct. 102 Development of epididymis, vas deferens and male accessory glands 102 Feminization of the genital ducts . . . . . . . . . . . . . . . 103 Regression of the epigenital and paragenital parts of the mesonephros 105 Development of the external genitalia 105 Masculinization of the external genitalia 106 Feminization of the external genitalia. . . . . 107 Genetic control and sex-differentiation 108 Control of gonadal development . . . . . . . 108 Control of paramesonephric duct regression . . 109 Androgens of the fetal testes: testosterone synthesis no

VIII

:I<'etal testosterone effects . . . . . . . . . . . . Steroid production by the fetal and perinatal ovary Phylogenesis of sex-determination ·Malformations affecting genital organs .. Syndromes related to a complete bilateral gonadal developmental failure

Pure gonadal dysgenesis (including XY-gonadal dysgenesis, Swyer's syndrome) True agonadism (agonadia) ....... . Anorchism (syndrome of "vanishing" testes)

Turner's syndrome and its variants Gonadal dysgenesis: complete form Gonadal dysgenesis: incomplete form. . .

Pseudo-Turner syndrome (Noonan syndrome) Ovarian dysgenesis and early ovarian failure associated with X-chromosome abnormalities in patients with a normal stature

46,X, i (Xp-)females ..... . Male pseudohermaphroditism (m. p.)

Mixed gonadal dysgenesis. . . . Bilateral testicular dysgenesis . . Unilateral testicular dysgenesis ("uterus in males") Dysgenetic gonadal tumors (gonadoblastomas)

Testosterone deficiencies syndromes . . . . . . . . Eunuchoid male pseudohermaphroditism . . . . . . Male pseudohermaphroditism with pseudo vaginal hypospadia Testosterone insensitivity syndromes . . .

Complete testicular feminization (t. fm.) Malformations of genital ducts

Mesonephric duct aplasia . . . Rokitanski-Kiistner syndrome. Vaginal atresia . . . . . . . Rudimentary uterus .....

Malformations of the external genitalia Hypospadias . . . . . . . . . . Androgen-independent (teratogenic) malformations of the external genitalia

Cryptorchism . . . . . . . . Female pseudohermaphroditism True hermaphroditism . . . Klinefelter's syndrome . . . Multi X Syndromes in Males Trisomy X in females. Trisomy 9 Syndrome. . . . Trisomy 13 Syndrome Cornelia de Lange Syndrome Fetal Face Syndrome (Robinow Syndrome) Hypertelorism-hypospadias Syndrome (Opitz) Hypospadias-Dysphagia Syndrome (G-syndrome) Leopard Syndrome ............ . Meckel Syndrome (Dysencephalia splanchnocystica) Multiple Pterygium Syndrome (Bonnevie-Ullrych Syndrome) Myotonic Dystrophy (Steinert Syndrome) ....... . Potter Syndrome (oligohydramnion syndrome) ..... . Prader-Willi Syndrome (Hypotonia-Hypometia-Hypogonadi8m-Obesity Syndrome) Russel-Silver Syndrome Smith-Lemli-Opitz-Syndrome

CHAPTER 6 ••••.•• The Hypophysis Cells of the adenohypophysis The neurohypophysis The hypophyseal hormones

Growth hormone (GH) Prolactin (PRL) .... Adrenocorticotropin (ACTH) Melanotropin (MSH) Thyrotropin (TSH)

IX

112 113 113 115 115 115 115 116 116 116 116 117

117 117 117 118 U8 119 119 119 120 120 121 121 121 122 122 122 122 123 124 124 124 125 126 126 127 127 127 127 127 128 128 128 128 128 128 128 128 129 129 129

130 130 134 137 137 137 138 140 140 142

Hypophyseal gonadotropins, FSH and LH . . . . . . . . . . . . . Vasopressin (AVP) ....................... .

Cerebral neuroendocrine complex and hypothalamic feedback Vasopressin and oxytocin. . . . . . . Vasopressin feedback system . . . . . Somatostatin and STH feedback system Prolactin feedback system. . . . . . . CRF and adrenocorticotropin feedback system TRF and TSH feedback system .... LH RF and FSH, LH feedback systems

Steroid sensitive areas of the brain. . Phylogenesis of the hypophysis Pathology

Hypophyseal aplasia . . . Pituitary dwarfism. . . . Anencephaly . . . . . . Doubling of the hypophysis Leprechaunism (Donohue Syndrome) .

CHAPTER 7 ..

The epiphysis.

CHAPTER 8 .. Pharyngeal derivatives. The thyroid Histogenesis ...... . Thyroidal hormones . . . . Thyroid function in the human fetus Placenta and fetal thyroidal function. Calcitonin Phylogenesis . . . . . . . . . Pathology ........ .

Thyroid duct remnants or cysts Thyroid aplasia and dysgenesis Congenital goiter and hypothyroidism Thyrotropin insensitivity . . . . . . Isolated TSH deficiency . . . . . . Syndrome of thyroid aplasia, cutis verticis gyrata and mental retardation Pendred syndrome Sipple syndrome .

CHAPTER 9 ... The parathyhroid gland Cells of the parathyroid (PTH cells) Parathormone (PTH) ..... Phylogenesis . . . . . . . . . Calcium homeostasis in pregnancy Calcium and cellular functions. Magnesium Phosphates Citrate .. Pathology

Ost90dysplasia cystica generalisata Absence of parathyroids and thymus . Hypoparathyroidism . . . . . . . . Errors in parathormone synthesis . . Albright's hereditary osteodystrophy.

x

143 145

systems. 145 146 146 147 147 147 148 148 149 150 151 151 152 152 154 154

155 155

157 157 158 161 164 165 166 168 168 169 169 169 170 171 171 171 171 171

172 172 173 175 176 176 176 177 177 178 178 178 178 178 178 179

CHAPTER 10 Enteroendocrine cells and pancreatic islets. The pancreas . . . . . . Development . . . . . . . Cells of the pancreatic islets . B·cells and insulin formation A·cells and glucagon . . . D·cells ........ . Pancreatic islets phylogeny Insulin and its metabolism Glucagon and its metabolism Glycemia in pregnancy and diabetes Modification in lipid metabolism in pregnancy Maternal diabetes and the diabetic fetopathy Diabetic fetopathy. . . . . . . . . . . . . Transient neonatal diabetes mellitus . . . . . Exomphalos·macroglossia.gigantisms syndrome Pancreatic agenesis . . . . . . . . . . . . Neonatal hypoglycemia, hyperinsulinism and absence of pancreatic alpha· cells

CHAPTER 11 Amnionic fluid as a hormonal compartment. Hormones

Estrogens .. Progesterone Pregnanediol Dehydroepiandrosterone (DHA) and 16·hydrohy-DHA Testosterone and dihydrotestosterone Pregnanetriol Cortisol hCG hCS FSH LH_ TSH Prolactin ACTH . hGH .. Oxytocin Epinephrine and norepinephrin Insulin ....... .

List of abbreviations

References

Subject index

XI

180 180 180 180 181 184 184 184 185 186 187 187 187 188 188 189 189 189

190 191 191 192 192 193 193 193 194 196 196 196 197 197 198 198 198 199 199 200 200 200

202

204

241

PREFACE

The study of prenatal development provides many clues for understanding the physiology as well as the pathogeny of malformations and many diseases. I became interested in the analysis of human development as a young medical student more than 30 years ago, and I have stayed in this field all my life. In my studies, I always tried to compare the events of different disciplines such as genetics, anatomy, bio­chemistry and physiology. I learned that the development of a structure is, under normal circumstances, strictly determined and that the development of structures always precedes their proper function. There are no changes in function without changes in structure. The life of every cell is genetically preprogrammed and the program may be modified by complicated interactions with environment. Recent progress in our knowledge is basicly related to technology. However, using all the tools of today's technology, we are still unable to understand the basic normal development.

After almost thirty years of work, I am trying to present a subjective review of the development of the human endocrine glands. I am presenting an image emerging from my experience. I personally studied several hundred human embryos using mostly anatomical, histochemical and some biochemical techniques. I found much additional information in the literature. However, there is so much different infor­mation available today that, using the limited brain capacity, I did not try to register all observations and discoveries, but I selected some which seemed to me to be the most important. The following books were the valuable sources of my information:

In genetics and congenital anomalies:

McKusick V. A.: Mendelian inheritance in man; catalogs of autosomal dominat, autosomal recessive and X-linked phenotypes. Baltimore, Johns Hopkins Press, 1975. Bergsma D. (Ed.) Birth defects, atlas and compendium. The National Foundation March of Dimes, Baltimore, Williams and Wilkins Co., 1973.

In embryology:

Keibel F. and Mall. F. P. (Eds.) Manual of human embryology. Philadelphia London, J. B. Lippincott Co., Vol. I, 1910, Vol. II, 1912. Streeter G. L.: Developmental horizons in human embryos. Contrib. Embryol. Carnegie Inst., Washington, 1951. O'Rahilly R.: Developmental stages in human embryos, including a survey of the Carnegie Collection. Carnegie Inst., Washington, 1973. Willis R. A.: The borderland of embryology and pathology. London, Butterworth, 1958.

XIII

In comparative anatomy and phylogenesis:

Kent G. C. h.: Comparative anatomy of the vertebrates. St. Louis, C. V. Mosby Co. 1969. Romer A. S. Parson T. S.: The vertebrate body. Philadelphia, London, Toronto, W. B. Saunders Co., 1977.

In biochemistry:

Harper H. A.: Review of physiological chemistry. 15th ed., Los Altos, California, Lange Med. Pub., 1975.

These references will generally not be mentioned in the text.

The first version of Human Fetal Endocrines appeared in Czech in 1977. Since then, much new information has emerged. I completely revised and re\Hite the manuscript for the English edition during my stay in Minneapolis as Visiting Professor in the Department of Obstetrics and Gynecology, University of Minnesota Medical School.

I am deeply grateful to Dr. K. A. Prem for his kind invitation to join the Depart­ment of Obstetrics and Gynecology, University of Minnesota. I also wish to express many thanks to Mrs. Blanka Faltinova, Miss Donna Lidstad and Mrs. Rachel Roverud for thcir linguistic and secretarial help.

XIV