Table Of ContentCONTRIBUTORS
R. J. ABLIN I. LEAV
R. L. BACON TEHMING LIANG
DAVID BRANDES SHUTSUNG LIAO
MARIO H. BURGOS W. I. P. MAINWARING
DAVID P. BYAR THADDEUS MANN
L. F. CAVAZOS JAIME A. MOGUILEVSKY
DONALD S. COFFEY ROBERTO NARBAITZ
SENMAW FANG MIKKO NIEMI
CHARLES J. FLICKINGER P. OFNER
EL WIN E. FRALEY JOSEPH EDWARD PARIS
JOHN T. GRAYHACK DAVID F. PAULSON
DIETER KIRCHHEIM PENTTI TUOHIMAA
I. LASNITZKI J. L. TYMOCZKO
EARL F. WENDEL
MALE ACCESSORY
SEX ORGANS
STRUCTURE AND FUNCTION IN MAMMALS
Edited by David Brandes
Departments of Pathology,
The Johns Hopkins School of Medicine and
Baltimore City Hospital
Baltimore, Maryland
ACADEMIC PRESS New York San Francisco London 1974
A Subsidiary of Harcourt Brace Jovanovich, Publishers
COPYRIGHT © 1974, BY ACADEMIC PRESS, INC.
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United Kingdom Edition published by
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Library of Congress Cataloging in Publication Data
Brandes, David.
Male accessary sex organs.
Includes bibliographies.
1. Generative organs, Male. 2. Hormones, Sex.
I. Title. [DNLM: 1. Genitalia, Male-Anatomy and
histology. 2. Genitalia, Male-Physiology. 3. Sex
hormones-Physiology. WJ700 B817m 1974]
QP253.B7 599'.01'6 73-18941
ISBN 0-12-125650-2
PRINTED IN THE UNITED STATES OF AMERICA
List of Contributors
Numbers in parentheses indicate the pages on which the DONALD S. COFFEY (307), Department of
authors' contributions begin. Pharmacology and Experimental Thera-
R. J. ABLIN (433), Immunobiology Section, peutics, The Johns Hopkins School of
Center for the Study of Prostatic Diseases, Medicine, Baltimore, Maryland
Division of Urology, Department of Surgery,
SENMAW FANG (237), College of Pharmacy,
Cook County Hospital and Graduate School
University of Utah, Salt Lake City, Utah
of Medicine; The Hektoen Institute for
Medical Research and the Department of CHARLES J. FLICKINGER (115), Department of
Microbiology, The Chicago Medical School/ Anatomy, School of Medicine, University of
University of Health Sciences, Chicago, Virginia, Charlottesville, Virginia
Illinois
ELWIN E. FRALEY (383), Division of Urology,
R. L. BACON (397), Department of Anatomy, University of Minnesota Hospitals, Min-
University of Oregon Medical School, neapolis, Minnesota
Portland, Oregon
JOHN T. GRAYHACK (425), Department of
Urology, Northwestern University Medical
DAVID BRANDES (17, 183, 223, 397, 469),
Departments of Pathology, The Johns School and Medical Center, Chicago, Illinois
Hopkins School of Medicine and Baltimore
DIETER KIRCHHEIM (397), Department of
City Hospitals, Baltimore, Maryland.
Urology, University of Washington Medical
MARIO H. BURGOS (151), Faculty of Medical School, Seattle, Washington
Sciences, Institute of Histology and Embryol-
I. LASNITZKI (347), Strangeways Research
ogy, U.N.C. Mendoza, Argentina
Laboratory, Wort's Causeway, Cambridge,
DAVID P. BYAR* (161), Department of Health, England
Education, and Welfare, National Institutes
I. LEAV(267), Department of Pathology, Tufts
of Health, National Cancer Institute,
University School of Medicine, Boston,
Bethesda, Maryland
Massachusetts
L. F. CAVAZOS (267), Department of Anatomy,
TEHMING LIANG (237), Ben May Laboratory
Tufts University, Boston, Massachusetts
for Cancer Research and Department of
Biochemistry, University of Chicago,
♦Present address: N. I. H., National Cancer Institute,
Landow Building, Room C-509, Bethesda, Maryland 20014. Chicago, Illinois
X LIST OF CONTRIBUTORS
SHUTSUNG LIAO (237), Ben May Laboratory for ory, Lemuel Shattuck Hospital; Department
Cancer Research and Department of Bio- of Urology, Tufts University School of
chemistry, University of Chicago, Chicago, Medicine; and Pharmacology Departments,
Illinois Harvard School of Dental Medicine and
Harvard Medical School, Boston, Massa-
W. I. P. MAINWARING (469), Androgen Physi-
chusetts.
ology Unit, Imperial Cancer Research Fund,
Lincoln's Inn Fields, London, England JOSEPH EDWARD PARIS (223), Department of
Therapeutic Radiology, Tufts University
THADDEUS MANN (173), Unit of Reproductive
School of Medicine, Boston, Massachusetts
Physiology and Biochemistry, University of
Cambridge, Cambridge, England DAVID F. PAULSON (383), Duke University
Medical Center, Durham, North Carolina
JAIME A. MOGUILEVSKY (133), Faculty of
Medicine, Section of Neuroendocrinology, PENTTI TUOHIMAA (329), Department of
Institute of Physiology, University of Buenos Anatomy, University of Turku, Turku,
Aires, Paraguay, Buenos Aires, Argentina Finland
ROBERTO NARBAITZ (3), Department of J. L. TYMOCZKO (237), Ben May Laboratory for
Histology and Embryology, Faculty of Cancer Research and Department of Bio-
Medicine, University of Ottawa, Ottawa, chemistry, University of Chicago, Chicago,
Ontario, Canada Illinois
MlKKO NlEMI (329), Department of Anatomy,
EARL F. WENDEL(425), Department of Urology,
University of Turku, Turku, Finland
Northwestern University Medical School and
P. OFNER(267), Steroid Biochemistry Laborat- Medical Center, Chicago, Illinois
Preface
For many years the mechanisms of action of androgenic treatment. It seemed appropriate at
sex hormones on target organs have been studied this juncture to try to integrate in a single
intensively in an attempt to elucidate the specific volume the salient features of subcellular
interactions which ultimately and most precisely structure and function of some sex hormone-
control the structure and function of cells in these dependent organs and of the molecular
organs. Much information has been generated hormonal mechanisms by which they are
by these studies on molecular mechanisms of controlled.
hormone action and their effects on the sub- Part I of this book presents detailed descrip-
cellular organization and functional expression tions of the ultrastructural organization, nutri-
of target cells. tional requirements, and chief functional pro-
Numerous recent reviews are available which perties of the main sex accessory glands in the
delineate various aspects of the harmonious male, whereas Part II is exclusively devoted to
modulation of the structural and functional molecular mechanisms of hormone action. Part
interplay between sex hormones and target III is concerned with immunological aspects
organs. Thus it has been shown that testosterone and systematic abnormalities of some of these
enters susceptible cells and becomes trans- organs. Included are both in vivo and in vitro
formed into active metabolic products by studies on prostatic carcinoma, one of the most
various enzymes. These metabolites in turn frequent and serious neoplasias occurring in
control the cell fabric for protein synthesis the male. The inability through the years to
contained in the ergastoplasm and free ribo- produce experimental prostatic carcinoma in
somes as well as the organelles responsible for vivo has shifted research efforts to possible
the elaboration and delivery of secretory pro- in vitro models through carcinogenesis, chemi-
ducts. Castration or the administration of cal or viral, or to cultured cell lines of human
antiandrogenic compounds is followed by prostatic cancer.
sequestration and degradation of the protein- We feel that the interdisciplinary approach
synthesizing machinery, and, consequently, by used in this book will result in a readily
a decrease and ultimately a cessation of specific available and current resource which will allow
secretory functions. These regressive changes biomedical scientists and pathologists to
can be favorably altered by androgen-replace- correlate their respective findings on the biology
ment therapy or discontinuance of anti- and pathology of these organs.
DAVID BRANDES
Chapter 1
Embryology, Anatomy, and Histology of the Male Sex
Accessory Glands
ROBERTO NARBAITZ
Embryology 3
A. Development of the Mesonephros and Derivatives 3
B. Development of the Urogenital Sinus and Derivatives 6
C. Contributions from Experimental Embryology 8
Anatomy and Histology 9
A. Epididymis 9
B. Vas Deferens and Ampullary Glands 10
C. Seminal Vesicles 10
D. Prostate 11
E. Other Accessory Glands 12
References 15
I. EMBRYOLOGY
develops as an excretory pathway for the testis
while the caudal portion continues to function
The development of the male accessory glands
as a kidney. In higher vertebrates, including
follows a similar pattern in most mammals. We
mammals, the mesonephros has been replaced
shall describe this process in the human embryo,
by a more complex kidney—the metanephros.
commenting on significant variations occurring
During embryogenesis, however, a mesonephros
in other species.
is also formed and in most cases functions as a
temporary excretory organ. Later in develop-
A. Development of the Mesonephros and
ment, when the metanephros replaces the
Derivatives
mesonephros in its excretory role, male embryos
The mesonephros is a primitive type of ex- retain part of the mesonephric system, which
cretory organ found in lower vertebrates includ- contributes to form the genital apparatus.
ing amphibia. In the adult amphibian, the The embryonic mesonephros consists of
cranial portion of the mesonephric apparatus numerous tubules forming the bulk of two large
4 ROBERTO NARBAITZ
crests running longitudinally along both sides descend. Before reaching the urogenital sinus,
of the dorsal mesenterium—the urogenital both crests make a 180° rotation in such a way
crests (Fig. 1). Each mesonephric tubule con- that the Mullerian ducts, which were lateral to
tacts a vascular glomerulus at one end and opens the Wolffian ducts, now become medial. On
into an excretory duct known as mesonephric reaching the sinus, the two Mullerian ducts, now
or Wolffian duct at the other. Each urogenital in close contact, fuse to form a single median
crest contains, in addition to the numerous structure (Fig. 4). Both Wolffian ducts open
mesonephric tubules and the Wolffian duct, the finally into the urogenital sinus at both sides of
primordium of a gonad (in its medial wall) and the fused Mullerian ducts.
another longitudinal duct, the Mullerian (para- In the human embryo, mesonephric tubules
mesonephric) duct, which is laterally situated start to form during the fourth week and well-
(Fig. 1). developed urogenital crests are present after the
Thus constituted, both urogenital crests run fifth week (Fig. 1). The Wolffian ducts reach the
caudally toward the cloacal region, and since cloacal region at the same time, while the Mul-
mesonephric tubules are not formed in the most lerian ducts are just beginning to form during the
caudal part, the crests become narrower as they
Fig. 1. Schematic ventrolateral
view of the urogenital system of a
human embryo in the seventh week.
(Reproduced by the courtesy of Pro-
fessors Hamilton, Boyd, and Mossman
and Heffer & Sons, Ltd., Cambridge,
England.)
1. EMBRYOLOGY, ANATOMY, AND HISTOLOGY 5
sixth week and reach the urogenital sinus by the ephric tubules will be referred to as efferent
ninth (Fig. 4). ductules.
By this time, the metanephros has completely
1. DIFFERENTIATION OF THE EPIDIDYMIS
replaced the mesonephros in its urinary func-
The gonadal primordia formed during the tions, and all mesonephric tubules which did not
early part of the fifth week remain undifferen- connect with the rete testis undergo atrophy. A
tiated until the seventh. At this time, in embryos few of them, however, may persist as function-
destined to become males, the primitive sex less rudiments in the neighborhood of the testis
cords transform into seminiferous cords (Gill- (paradidymis and appendix of the epididymis).
man, 1948; Van Wagenen and Simpson, 1965). The portion of the Wolffian duct situated
Shortly thereafter, the distal ends of the semi- cranial to the gonad atrophies gradually, but
niferous cords interconnect, forming a network the rest persists; the middle region, which re-
of solid cords known as the rete testis. Since the ceives the efferent ductules, grows very quickly,
gonad is situated on the medial side of the folding repeatedly upon itself (Fig. 2B), thereby
urogenital crest, the rete testis lies in direct forming the ductus epididymis. The efferent
contact with the mesonephric tubules contained ductules and the ductus epididymis together
in the crest (Fig. 1 and 2A). During the third constitute the organ known as the epididymis.
month of development, the rete testis begins to The differentiation of the epididymis in other
make connections with the neighboring me- mammalian groups follows a pattern similar to
sonephric tubules, and by the sixth month, the the one just described for the human embryo.
cords of the rete testis start to acquire a lumen In many rodents, however, the epididymis lies
which becomes continuous with that of the somewhat separated from the testis, and the
mesonephric tubules (Fig. 2B). These meson- efferent ductules fuse to form a single tube before
reaching the ductus epididymis. This tube prob-
ably derives from the Wolffian duct (Raynaud,
1969).
2. DIFFERENTIATION OF THE DEFERENT DUCT
AND SEMINAL VESICLES
It has been mentioned previously that while
the cranial portion of the Wolffian duct under-
goes atrophy, the middle part transforms into
the ductus epididymis. The fate of the caudal
portion of the duct is as follows:
In the thirteenth week an evagination of the
duct forms in the neighborhood of the uro-
genital sinus, constituting the primordium of the
(A) (B)
seminal vesicle (Fig. 2B). This evagination
divides the caudal portion of the Wolffian duct
Fig. 2. Schematic illustration of the development of the
in two sections: the deferent duct and the
derivatives of the mesonephric apparatus. (A) At the
beginning of the third month. (B) After the fourth month ejaculatory duct. The primordium of the seminal
(prostatic cords growing from the urogenital sinus have vesicle is at first a straight tube; it later branches
been ommitted for the sake of simplicity). B.L., bladder; into three or four very convoluted ducts which,
D.D., deferent duct; D.E., ductus epididymis; E.D.,
held together by a common mesodermic stroma,
efferent ductules; M.T., mesonephric tubules; S.C., semi-
constitute the seminal vesicle. Differentiation
niferous cords; S.V., seminal vesicles; U.G.S., urogenital
sinus; W.D., Wolffian duct; T.; testis; R.T., rete testis. is completed by the seventh month.
6 ROBERTO NARBAITZ
The rabbit has a single median seminal
vesicle. This structure was previously interpreted
as an enlarged utriculus prostaticus derived from
the fused portion of Mullerian ducts. Careful
studies have demonstrated, however, that the
structure is derived from the fusion of two lateral
primordia evaginated from the Wolffian ducts;
it thus originates along the lines of the seminal
vesicles in other mammals (Raynaud, 1969).
Large ampullary glands are formed in rodents
by evagination of the Wolffian duct.
B. Development of the Urogenital Sinus and
Derivatives
A septum growing from its cephalic to its
Fig. 4. Urogenital sinus of a nine-week human embryo.
caudal end will divide the endodermic cloaca
(Reproduced from Arey, 1965.)
into dorsal and ventral compartments. This
process starts in the human embryo at the fourth
The pelvic portion receives the Wolffian and
week and is complete by the seventh. The result-
Mullerian ducts in its dorsal wall (Figs. 3 and 4).
ing dorsal subdivision will constitute the rectum.
This is a very complex region as structures of
The ventral cavity will show a dilated cephalic
three different origins meet here. It is accepted
part constituting the bladder and a narrower
(Chwalla, 1927; Gyllensten, 1949) that the
caudal tube, the urogenital sinus (Arey, 1965;
growing sinus produces the resorption of part
Patten, 1968). The cloacal membrane, which
of the Wolffian ducts in such a way that a small
originally obturated the caudal end of the
zone of the sinus and the bladder is temporarily
cloaca, disappears by the seventh week, when
lined with Wolffian epithelium. Similarly, it
the partition has been completed. At this time
is believed that cells of Mullerian origin may
or shortly after, two portions can be distinguish-
intermingle with epithelial cells of the urogenital
ed in the urogenital sinus: the tubular cephalic
sinus in the zone of the Mullerian tubercle
portion connected with the bladder (pelvic
(Fig. 4). It is thus very difficult to establish the
urethra) and the open groove at the base of
real cellular origin of structures formed later
the genital tubercle (phallic urethra) (Fig. 3).
from this portion of the sinus. The practical
implications of this problem become apparent
in the discussion of the differentiation of the
prostate.
1. DIFFERENTIATION OF THE PROSTATE
The prostatic gland is formed from the
cephalic portion of the urogenital sinus in the
region tha« Mullerian and Wolffian ducts
open into. The glands constituting the prostate
appear as solid branching cords growing from
the sinusal epithelium into the surrounding
mesoderm. Thus, the ejaculatory ducts, derived
Fig. 3. Model illustrating the caudal portion of a
nine-week human embryo. (Reproduced from Arey, 1965.) from the Wolffian ducts, and the blind sac
