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[[Book - Comparative Embryology of the Vertebrates 1|'''Part I - The Period of Preparation''']]: [[Book - Comparative Embryology of the Vertebrates 1-1|1. The Testis and Its Relation to Reproduction]] | [[Book - Comparative Embryology of the Vertebrates 1-2|2. The Vertebrate Ovary and Its Relation to Reproduction]] | [[Book - Comparative Embryology of the Vertebrates 1-3|3. The Development of the Gametes or Sex Cells]]
[[Book - Comparative Embryology of the Vertebrates 1|'''Part I - The Period of Preparation''']]: [[Book - Comparative Embryology of the Vertebrates 1-1|1. The Testis and Its Relation to Reproduction]] | [[Book - Comparative Embryology of the Vertebrates 1-2|2. The Vertebrate Ovary and Its Relation to Reproduction]] | [[Book - Comparative Embryology of the Vertebrates 1-3|3. The Development of the Gametes or Sex Cells]]


The events which precede the initiation of the new individual's development are:
=The Vertetrate Ovary and Its Relationship to Reproduction=
==A. The Ovary and Its Importance==


# The preparation of the male and female parents and their reproductive structures for the act of reprcxluction (Chaps. [[Book - Comparative Embryology of the Vertebrates 1|1]] and [[Book - Comparative Embryology of the Vertebrates 2|2]]).  
One of the editions of the treatise on development, “Exercitationes de
# The preparation of the gametes ([[Book - Comparative Embryology of the Vertebrates 3|Chap. 3]]).  
Generatione Animalium,” by William Harvey (1578-1657) contains a picture of Jupiter on a throne opening an egg from which various animals,
including man, are emerging (fig. 25). Upon the egg (ovum) are engraved
the words ovo omnia.'' At the heading of chapter 62 of this work Harvey
placed a caption which explains the phrase ex ovo omnia more explicitly.  
This heading reads: “Ovum esse primordium commune omnibus animalibus”
— the egg is the primordium common to all animals. Published in 1651, this
statement still maintains its descriptive force.  


The anterior lobe of the pituitary gland, because of its secretion of the gonadotrophic (gonad-stimulating) hormones, is the pivotal structure in the reproductive mechanism.  
Many individual animals arise by asexual reproduction, that is, through
a process of division or separation from a parent organism. In the phylum
Chordata asexual reproduction is found among the Urochordata, where new individuals may arise by budding from a stolon -like base of the parent (fig.
27). This process often is called gemmation, the formation of a new individual by a protrusion of a mass of cells from the parental body followed by
its partial or complete separation. It is a prominent method of reproduction
among the lower Metazoa, particularly the coelenterates and sponges. Nevertheless, all animal species among the Metazoa ultimately utilize an egg as
the primordium from which the new individual arises. Sexual reproduction,
generally associated with the fertilization of an egg by a sperm element, appears
to be a needful biological process.  


The gonadotrophic hormones are:
# Follicle-stimulating hormone, FSH;
# Luteinizing hormone, LH (ICSH), and
# Luteotrophin, LTH.


==The Testis and Its Relation to Reproduction==
===A. Introduction===
====1. General Description of the Male Reproductive System====


The male reproductive system of most vertebrate animals consists of two testis with a sperm-conveying duct and attendant auxiliary glands associated with each testis. In some species, such as the frog and many teleost fishes, the sperm-conveying duct is a simple structure, but in most vertebrate forms there is a tendency for the duct to be complicated. The cyclostomatous fishes do not possess sperm-conveying ducts from the testis to the outside.


In reptiles, some birds and all mammals, in gymnophionan amphibia and in the “tailed” frog, Ascaphus, in sharks and certain teleost fishes, an intromittent organ is added to the sperm-conveying structures for the purpose of internal fertilization. But an intromittcnt organ is not present in all species which practice internal fertilization. In many salamanders, internal fertilization is effected by the spawning of a spermatophore filled with sperm; the latter is picked up by the cloaca of the female. The sperm in these salamanders are stored in special pockets or tubules within the dorsal wall of the cloaca. These storage tubules form the spermatheca (fig. 10). Direct transfer of sperm to the female by cloacal contact may occur in some species.
Fig. 25. Copy of the engraved title appearing in one edition of Harvey’s dissertation
on generation as shown on p. 139 of Early Theories of Sexual Generation by E. J. Cole.  
Observe the words “ex ovo omnia” upon the egg which Jupiter is opening. Various animals
are emerging from the egg.  


====2. Importance of the Testis====
Fig. 26. Copy of Hartsoeker’s figure of human spermatozoan, containing the homonculus or “little man,” published in 1694. This figure represents a marked preformationist
conception of development. However, it is to be noted that Hartsoeker later abandoned
the preformationist concept as a result of his studies on regeneration.


The word testis or testicle was formerly applied to the ovary of the female, as well as to the male sperm-producing organ, and the term "female testicle" was used in reference to the female organ. The use of the word “ovary” was introduced by Steno in 1667, and also by de Graaf (fig. 1 ) in 1672 in his work on the female generative organs. To quote from de Graaf: “Thus, the general function of the female testicles is to generate the ova, to nourish them, and to bring them to maturity, so that they serve the same purpose in women as the ovaries of birds. Hence, they should rather be called ovaries than testes because they show no similarity, either in form or contents, with the male testes properly so called.” (See Corner, -43.) From the time of de Graaf the word “testis” has been restricted to designate the male organ essential to reproduction.




The phrase "essential to reproduction" does not describe fully the importance of testicular function. As we shall see later on, the testis not only assumes the major role in the male's activities during the period of reproduction, but also, in the interim between specific reproductive periods, it governs in many instances male behavior leading to protection and preservation of the species. Thus, the testis is the organ responsible for maleness in its broader, more vigorous sense.


===B. Anatomical Features of the Male Reproductive System===
True as the general statement made by Harvey may be, it is not clear what
Before endeavoring to understand the general functions of the testis in relation to reproduction, it is best to review some of the structural relationships of the testis in the vertebrate group.
is meant by the word ovum or egg. We know certain of its characteristics,
 
but, for the most part, it must be accepted as an accomplished fact enshrouded
 
in mystery. To Harvey the egg was an indefinite, unorganized association of
 
substance plus a “primordial generative principle” (see Cole, F. J., ’30, p.
Fig. 1. Reinier de Graaf. Born in Holland, 1641; died in Delft, Holland, 1673. Author of important works on the generative organs of the female. Described the Graafian follicle in the ovary of mammals but erroneously believed it to be the mammalian egg. (From Corner, '43.)
140), Other minds have conceived of other meanings. Nevertheless, descriptive
 
and experimental embryology has forced the conclusion that the egg, during
====1. Anatomical Location of the Testis====
its development within the ovary, experiences a profound process of differentiation, resulting in the formation of an invisible organization. Although this organization is invisible, it is imbued with an invincibility which, when
set in motion at the time of fertilization, drives the developmental processes
onward until final fulfillment is achieved in the fully formed body of the
adult organism.  


In most vertebrates other than mammals, the testes are suspended well forward within the peritoix eal^cayity. In the Mammalia, however, the condition is variable. In the monotrematous mammals. Echidna and Ornithorynchus, the testes are located within the peritoneal cavity near the kidneys. In the elephant the testes also are located in this area. Schulte (’37) describes the position of the testes in an Indian elephant (Elephas indicus), 20 years old, as being “retroperitoneal lying on each side medial to the lower pole of the kidney.” (The kidneys were found to lie retroperitoneally on either side of the lower thoracic and lumbar vertebrae, and each measured about 275 mm. in length.) However, in the majority of mammals the testes descend posteriad from the original embryonic site, the extent varying with the species. In some there is a slight posterior migration, and the testes of the adult are situated well forward in the pelvic region. Examples of this condition are found in conies, whales, sea cows, African jumping shrews, and in armadillos. In sloths and American anteaters, the testes may descend into the pelvic cavity and lie in the area between the urinary bladder and the posterior body wall. However, in most of the eutherian and marsupial mammals, a dual outpushing of the postero-ventral body wall occurs into which the testes come to lie either permanently, or, in some forms, temporarily during the breeding season. This outward extension of the body-wall tissues is known as the scrotum; it involves not only the skin, muscle and connective tissues of the body wall but the peritoneal lining as well (fig. 2). (The interested student may consult Weber (’28) and Wislocki (’33) for data concerning the extent of testis descent in mammals.)




The peritoneal evaginations into the scrotal sac are two in number, one for each testis; each evagination is known as a processus vaginalis (figs. 3E, F; 4A, B). In many mammals this evagination becomes separated entirely froln the peritoneal cavity, and the testis, together with a portion of the sperm-conveying duct, lies suspended permanently in a small antechamber known as the inguinal bursa or serous cavity of the scrotum (fig. 4B). (See Mitchell, ’39.) This condition is found in the horse, man, opossum, bull, ram, dog, cat, etc. In certain other mammals, such as the rat, guinea pig, and ground hog, the inguinal bursa does not become separated from the main peritoneal cavity, and a persistent inguinal canal remains to connect the inguinal bursa with the peritoneal cavity (fig. 4C). In some rodents the testes pass through this persisting inguinal canal into the scrotum as the breeding season approaches, to be withdrawn again after the breeding period is terminated. The ground squirrel, Citellus tridecemlineatus (Wells, ’35) and the ground hog, Marrnota monax (Rasmussen, ’17) are examples of mammals which experience a seasonal descent of the testis.
Fig, 27. Forms of asexual reproduction in the subphylum Urochordata 9 #


Chordata. (From MacBride: Textbook of Embryology, Vol. 1, Londo/rt', ^


In the majority of those mammals possessing a scrotum, it is a permanent structure. In a few, however, it is a temporary affair associated with the breeding season, as in the bat, Myotis, where the testes pass into a temporary perineal pouch or outpushing of the posterior abdominal wall during the reproductive season, to be withdrawn again together with the scrotal wall when the breeding period is past (fig. 4D). A similar periodic behavior is true of many insectivores, such as the common shrews, the moles, and the European hedgehog (Marshall, ’ll).
(A) Budding from "stolon of Perophora listeri, from MacBride after (jR) , (C)  


Two stages of budding in an ascidian, from MacBride after Pizon




Fig. 2. Sketch of male reproductive system in man.


Beyond the fundamental changes effected in the developing egg while in
the ovary, the latter structure has still other roles to maintain. Through the
mediation of the hormones produced within the confines of the ovarian substance, the female parent is prepared to assume the responsibilities of reproduction. In addition, in many vertebrates the further responsibility of taking
care of the young during the embryonic period stems from the hormones
produced in the ovary. In some vertebrates, the instinct of parental care of
the young after hatching or after birth indirectly is linked to ovarian-pituitary
relationships. Because of these profound and far-reaching influences which
the ovary possesses in producing the new individual, it must be regarded as
the dynamic center of reproduction for most animal species.


The permanent scrotum is a pendent structure, in some species more so than others. In the bull and ram, it extends from the body for a considerable distance, whereas in the cat, hippopotamus, tapir, guinea pig, etc., it is closely applied to the integumentary wall. In primates, including man, in most carnivores, and many marsupials, the pendency of the scrotum is intermediate between the extremes mentioned above.
==B. Preformationism, Past and Present==
 
An exceptional anatomical position of the testes in the lower vertebrates is found in the flatfishes, such as the sole and flounder, where they lie in a caudal outpouching of the peritoneal cavity (fig. 5). The testis on either side may even lie within a special compartment in the tail. (The ovaries assume the latter position in the female.)
 
 
 
Fig. 3. Diagrammatic representations of the urogenital structures in the developing male pig, with special emphasis upon testicular descent. (A) Early relationship of the genital fold (genital ridge), mesonephric kidney and its duct, together with the metanephric kidney and the ureter in 20-mm. pig embryo. The relationship of the mesonephric and metanephric ducts to the urogenital sinus is shown. The Miillcrian duct is omitted. (B) Male pig embryo about 45-mm., crown-rump length, showing relationship of gonad and metanephric kidney. I he metanephric kidney is shown below (dorsal to) the mesonephric kidney. The gonad (testis) is now a well-defined unit. The portion of the genital fold tissue anterior to the testis becomes the anterior suspensory ligament of the testis, while the genital fold tissue caudal to the testis continues back to join the inguinal ligament of the mesonephros (the future gubernaculum). (C) About 80-mm., crown-rump, pig embryo. Observe that the metanephros is now the dominant urinary organ and has grown cephalad, displacing the mesonephric kidney which is regressing and moving caudally with the testis. The remains of the mesonephric kidney at this time are gradually being transformed into epididymal structures. (D) About 130~mm.. crown-rump, pig embryo. Observe that the testis is approaching the internal opening of the inguinal canal. The anterior suspensory ligament is now an elongated structure extending over the lateroventral aspect of the metanephric kidney; the gubernacular tissue is shown extending downward into the inguinal canal. (E) Later stage in testicular descent. The anterior suspensory ligament of the testis is a prominent structure, while the gubernaculum is compact and shortened. (F) The condition found in the full-term, fetal pig. The testis is situated in the scrotal swelling; the gubernaculum is much shortened, while the anterior suspensory ligament remains as a prominent structure, extending cephalad to the caudal portions of the metanephric kidney.
 
 
2. Possible Factors Involved in Testis Descent The descent of the testis within the peritoneal cavity and into the scrotum poses an interesting problem. In embryonic development extensive migration of cell substance, or of cells, tissues, and organ structures is one of many processes by which the embryonic body is formed. That is to say, the dynamic movement or displacement of developing body structures from their original position is a part of the pattern of development itself. The casual factors involved in such movements are still unknown, and the study of such behavior forms one of the many interesting aspects of embryological investigation awaiting solution.


The above statement relative to the importance of ovarian influences and
of the female parent is a position far removed from that held by some in the
past. An ancient belief elevated the male parent and his “seed” or semen.
As Cole, F. J., ’30, p. 38, so aptly places the thinking of certain learned
sources during the 16th century: “The uterus is regarded as the ‘till’d ground
for to sow the seeds on’ — a popular idea, based obviously on the analogy
with plants, which prevailed long before and after this period. The seed of
the male is therefore the chief agent in generation, but cannot produce an
embryo without the cooperation of the female, and whether the result is male
or female depends on which side of the uterus the seed falls, the time of the
year, temperature, and the incidence of menstruation.” Or, in reference to
the Leeuwenhoek’s belief in an intangible preformationism, Cole, F. J., ’30,
p. 57, states: “He asserts that every spermatic animalcule of the ram contains
a lamb, but it does not assume the external appearance of a lamb until it has
been nourished and grown in the uterus of the female.” This statement of
A. van Leeuwenhoek (1632-1723) was made as a criticism of N. Hartsoeker
(1656-1725) whose extreme adherence to a seminal preformationism led
him to picture the preformed body of the human individual, the homonculus,
encased within the head of the spermatozoon (fig. 26). Hartsoeker, however,
later abandoned this idea.


In fairness it should be observed that the egg during these years did not
lack champions who extolled its importance. While the Animalculists considered the sperm cell as the vital element in reproduction, the Ovists, such as
Swammerdam (1637-80), Haller (1708-77), Bonnet (1720-93) and Spallanzani (1729-99) believed that the pre-existing parts of the new individual
were contained or preformed within the egg.


Fig. 4. Diagrammatic drawings portraying the relationship of the testis to the processus vaginalis (peritoneal evagination) and the scrotum. The testis is at all times retroperitoneal, i.e., outside the peritoneal cavity and membrane. (A) Earlier stage of testicular descent at the time the testis is moving downward into the scrotum. (B) Position of the testis at the end of its scrotal journey in a form possessing permanent descent of the testis, e.g., man, dog, etc. (C) Testis-peritoneal relationship in a form which does not have a permanent descent of the testis — the testis is withdrawn into the peritoneal cavity at the termination of each breeding season. Shortly before the onset of the breeding period or “rut,” the testis once again descends into the scrotum, e.g., ground hog. (D) Position of testis in relation to body wall and peritoneum in the mole, shrev/, and hedgehog in which there is no true scrotum. The testis bulges outward, pushing the body wall before it during the breeding season. As the testis shrinks following the season of rut, the bulge in the body wall recedes. True also of bat, Myotis.


An extreme form of preformationism was advocated by certain thinkers
during this period. For example, Bonnet championed the idea of encasement
or “emboitement.” To quote from Bonnet:


Fig. 5. Opened peritoneal cavity of a common flounder, Limanda ferruginea, showing the position occupied by the testes. Each testis is situated partly in a separate compartment on either side of the hemal processes of the tail vertebrae.
The term “emboitement” suggests an idea which is not altogether correct. The
germs are not enclosed like boxes or cases one within the other, but a germ forms
part of another germ as a seed is a part of the plant on which it develops. This
seed encloses a small plant which also has its seeds, in each of which is found a  
plantule of corresponding smallness. This plantule itself has its seeds and the latter
bears plantules incomparably smaller, and so on, and the whole of this ever
diminishing series of organized beings formed a part of the first plant, and thus
arose its first growths. (Cole, ’30, p. 99.)


On the other hand, there were those who maintained that for some animals,
neither the sperm nor the egg were important as “many animals are bred
without seed and arise from filth and corruption, such as mice, rats, snails,
shell fish, caterpillars, moths, weevils, frogs, and eels” (Cole, ’30, p. 38).
This concept was a part of the theory of spontaneous generation of living
organisms -a theory ably disproved by the experimental contributions of
three men: Redi (1626-97); Spallanzani; and Louis Pasteur (1822-95).


Various theoretical explanations have been proposed, however, to explain the movement of the testis posteriad from its original embryonic site. Classical theory mentions the mechanical pull or tightening stress of the gubernaculum, a structure which develops in relation to the primitive genital fold or genital ridge (figs. 3B, C; 351C-7).
Modern embryology embraces a kind of preformationism, a preformationism which does not see the formed parts of the new individual within
 
the egg or sperm but wi.ich does see within the egg a vital, profound, and
highly complex physiochemical organization capable of producing a new individual by a gradual process of development. This organization, this selfdetermining mechanism, is resident in the nucleus with its genes and the
organized cytoplasm of the fully developed oocyte or egg. However, as shown
later, this organization is dependent upon a series of activating agencies or
substances for its ultimate realization. Some of these activating substances
come from without, but many of them are produced within the developing
organism itself.


The genital ridge extends along the mesial aspect of the early developing mesonephric kidney from a point just caudal to the heart to the posterior extremity of the mesonephric kidney near the developing cloacal structures (Hill, ’07). Anteriorly, the genital ridge (fold) merges with the diaphragmatic ligament of the mesonephros (fig. 3A). The gonad (testis or ovary) develops in a specialized region of the more cephalic portion of the genital ridge (Allen, ’04). (See fig. 3A.) The caudal end of the mesonephric kidney eventually becomes attached to the posterior ventral body wall by means of a secondary formation of another cord of tissue, the inguinal fold (fig. 3A). The latter is attached to the posterior ventral body wall near the area where the scrotal outpushing (evagination) later occurs. This inguinal fold later becomes continuous with the genital fold (fig. 3B). The inguinal fold thus becomes converted into a ligament, the inguinal ligament of the mesonephros, uniting the caudal portion of the mesonephric kidney and adjacent genital fold tissue with the area of scrotal evagination (fig. 3B). The gubernaculum represents a later musculo-connective tissue development of the inguinal ligament and the adjacent genital fold tissue. It contains smooth muscle fibers as well as connective tissue. As the scrotal evagination forms at the point where the gubernaculum attaches to the body wall, the gubernaculum from the beginning of its formation is connected with the developing scrotal sac.
==C. General Structure of the Reproductive System of the Vertebrate Female==


===1. General Structure of the Ovary===


As the testis migrates posteriad, the anterior suspensory ligament of the testis elongates and the gubernaculum shortens (fig. 3A~F). This decrease in length of the gubernaculum is both real and relative. It is real in that an actual shortening occurs; it is relative because the rapid enlargement of the developing pelvic cavity and its contained organs makes the length of the gubernaculum appear less extensive. This enlargement of the pelvic space and increase in size of its contained structures and a corresponding failure of the gubernaculum to elongate, certainly are factors in bringing about the intra-abdominal descent of the testis; that is, testis descent within the peritoneal cavity itself (Felix, '12).
Morphologically, the ovary presents a series of contrasts in the different
vertebrate classes. In teleost fishes the size of the ovary is enormous compared
to the body of the female (fig. 28), while in the human (fig. 29), cow, sow,
etc., it is a small structure in comparison to the adult body. Again, it may
contain millions of mature eggs in the ling, cod and conger, during each breeding season, whereas only a single egg commonly is matured at a time in the  
cow, elephant, or human. During the reproductive season the ovary may
assume a condition of striking colored effects as in the bird, reptile, shark,
and frog, only to recede into an appearance drab, shrunken, and disheveled
in the non-breeding season.  




Developmental preparations precede the extra-abdominal descent of the testes, for the scrotal chambers must be prepared in advance of the arrival of the testes. These developmental events are:


(1) two outpocketings of the abdominal wall which come to lie side by side below the skin to form the walls of the scrotal chamber, and
Fig. 28. Dissection of female specimen of the common flounder, Limanda ferruginea.
It particularly shows the ovary with its laterally placed ovarian sinus. Observe that the
ovary, during the breeding season, is an elongated structure which extends backward into
the tail. There are two ovaries, one on either side of the hemal processes of the caudal
vertebrae.


(2) an evagination of the peritoneum into each of the abdominal outpocketings which act as peritoneal linings for each pocket.
Its shape, also, is most variable in different species. In mammals it is a
 
flattened ovoid structure in the resting condition, but during the reproductive
It is worthy of mention that the above outpushings of the abdominal wall and of the peritoneum precede the movement of the testes into the scrotum. They serve to illustrate the theory that a shortening of the gubernaculum is not sufficient to explain testis descent. Rather, that in this descent a whole series of developmental transformations are involved; the shortening of the gubernaculum and scrotal development merely represent isolated phases of the general pattern of movement and growth, associated with this descent.
phase it may assume a rounded appearance, containing mound-like protrusions.  
 
In birds and reptiles it has the general form of a bunch of grapes. In the  
More recent research emphasizes the importance of certain physiological factors relative to the descent problem. It has been determined, for example, that administration of the gonadotrophic hormone of pregnancy urine (chorionic gonadotrophin) or of the male sex hormone, testosterone, aid the process of extra-abdominal descent (i.c., descent from the inguinal ring area downward into the scrotum) . Hormone therapy, using chorionic gonadotrophin together with surgery, is used most often in human cryptorchid conditions. The androgen, testosterone, aids testicular descent mainly by stimulating the growth of the scrotal tissues and the vas deferens; however, it is not too successful in effecting the actual descent of the testis (Robson, '40; Wells, '3; Pincus and Thimann, '50).
amphibia it may be composed of a series of lobes, each of which is a mass
of eggs during the breeding season, and in teleost and ganoid fishes it is  
an elongated structure extending over a considerable area of the body.  


The phenomenon of testicular migration thus is an unsolved problem. Many activities and factors probably play a part in ushering the testis along the pathway to its scrotal residence.
Regardless of their many shapes and sizes, the ovaries of vertebrates may
be divided morphologically into two main types, namely, compact and saccular
forms. The compact type of ovary is found in teleost, elasmobranch, cyclostome, ganoid, and dipnoan fishes, as well as in reptiles, birds and mammals.
It has the following regions (figs. 30, 31):


====3. General Structure of the Scrotum and the Testis in Mammals====
# the medulla, an inner zone containing relatively large blood and lymph vessels;
# the cortex, an area outside of and surrounding the medulla (except at the hilus), containing many ova in various stages of development;
# a tunica albuginea or connective-tissue layer surrounding the cortex;
and  
# the germinal epithelium or the covering epithelium of the ovary.


a. Structure of the Scrotum
The germinal epithelium is continuous with the mesovarium, the peritoneal
support of the ovary, and the particular area where the mesovarium attaches
to the ovary is known as the hilus. Within the mesovarium and passing
through the hilus are to be found the blood and lymph vessels which supply
the ovary (fig. 30).


The scrotal modification of the body wall generally occurs in the posteroventral area between the anus and the penial organ. However, in marsupials it is found some distance anterior to the latter.
The ovary of the teleost fish is a specialized, compact type of ovary adapted
to the ovulation of many thousands, and in pelagic species, millions of eggs
at one time. It has an elongate hilar aspect which permits blood vessels to
enter the ovarian tissue along one surface of the ovary, whereas the opposite
side is the ovulating area. In many teleosts the ovulating surface possesses
a special sinus-like space or lumen (fig. 28) which continues posteriad to
join the very short oviduct. At the time of ovulation the eggs are discharged
into this space and move caudally as the ovarian tissue contracts. In other
teleosts this ovulatory space is not a permanent structure but is formed only
at the time of ovulation. In Tilapia macrocephala, for example, the ovulatory
lumen is formed on the side of the ovary opposite the area where the blood
vessels enter. The formation of this space at the time of ovulation is described
by Aronson and Holz-Tucker (’49) as a rupture of the elastic follicles during
ovulation whereupon the follicle walls shrink toward the ovarian midline.  


Each scrotal evagination consists of three general parts: the skin with certain attendant muscles, the structures of the body wall below the skin, and the peritoneal evagination. The skin, with its underlying tunica daitos muscle tissue and superficial perineal fascia, forms the outer wall of the scrotum (fig. 6). Within this outer cutaneous covering lie the two body-wall and two peritoneal evaginations. The body-wall evaginations involve connective and muscle tissues of the external oblique, internal oblique, and trans versus muscles. The caudal part of each peritoneal outpocketing forms the serous cavity or inguinal bursa in which the testis is suspended after its descent, and its more anterior portion forms the inguinal canal (figs. 2, 4B, 6). The oblique and transversus layers of tissues thus are molded into a musculo-connective tissue compartment around each serous cavity. The median septum of the scrotum represents the area of partial fusion between the two musculo-connective tissue compartments, whereas the median raphe of the scrotum denotes the area of fusion of the two cutaneous coverings of the body-wall outpushings (fig. 6).




Consequently, passing inward from the superficial perineal fascia of the skin or outer wall, one finds the following tissue layers surrounding the testis:
Fig. 29. Diagrammatic representation of a midsagittal section of the reproductive organs of the human female. (Slightly modified from Morris: Human Anatomy, Philadelphia, Blakiston.)


# The external spermatic fascia represents the modified fascia of the external oblique muscle layer of the embryo.
# The middle spermatic fascia is a modification of the internal oblique muscular layer, whose tissue forms the cremaster muscle loops within the scrotum (fig. 6). (Some of the cremasteric musculature may be derived from the transversus layer.)
# The internal spermatic fascia or tunica vaginalis communis is derived from the transverse muscle layer of the embryo.
# Along the inner surface of the tunica vaginalis communis is the peritoneal membrane. The latter is reflected back over the surface of the suspended testis, and thus forms the visceral peritoneal covering of the testis. This lining tissue of the common vaginal tunic and the peritoneal membrane which covers the testis are derived from the original peritoneal evagination into the scrotal pocket; as such it forms the tunica vaginalis propria*


b. General Structure of the Testis
[[File:Nelsen1953 fig030.jpg|600px]]


The testis is composed of the following structural parts:
'''Fig. 30.''' Schematic three-dimensional representation of the cyclic changes which occur in the mammalian ovary.


(1) The inner layer of the tunica vaginalis propria, the tunica vaginalis internus, envelops the testis. The cavity between the outer and inner layers of the tunica vaginalis propria is the inguinal bursa. Obliteration by injury or infection of this inguinal bursa may cause degenerative changes in the testis. In other words, the testis normally must be free to move within its serous (peritoneal) cavity.
(2) Within the tunica vaginalis internus of the testis is a thick fibrous layer of connective tissue, the tunica albuginea (fig. 7). From this tunic, connective tissue partitions, the septula of the testis, extend inward and converge toward that testicular zone where supplying blood vessels enter and leave, including the lymphatics. The latter zone is known as the mediastinum testis and it represents a regional thickening of the tunica albuginea. Here the connective tissue fibers form a latticework which acts as a framework for the larger blood and lymph vessels and efferent ducts of the testis. The testis is attached to the scrotal wall in the mediastinal area.
(3) The spaces between the various septula partitions form the septula compartments. In the human testis there are about 250 septula compartments, each containing a lobule of the testis. The lobuli testis contain the convoluted portions of the seminiferous tubules. From one to three seminiferous tubules are found in each lobule; they may anastomose at their distal ends. The combined length of all the seminiferous tubules approaches 250 meters in the human. The convoluted portions of the seminiferous tubules empty into the straight tubules (tubuli recti) and these in turn unite with the rete tubules located within the substance of the mediastinum. Connecting with the rete tubules of the testis, there are, in man, from 12 to 14 ductuli efferentes (efferent ductules of the epididymis) of about 4 to 6 cm. in length which emerge from the mediastinum and pass outward to unite with the duct of the epididymis. The epididymal duct represents the proximal portion of the reproductive duct which conveys the male gametes to the exterior.


carrying the interstitial tissue and immature ova. This shrinking away of the
tissues of the ovary leaves a space between these tissues and the outside
ovarian wall. A lumen thus is formed along the lateral aspect of the ovary
which is continuous with the oviduct. Many teleosts have two ovaries (e.g.,
flounder); in others there is but one (e.g., perch).


Fig. 6. Schematic drawing of the testis and its relationship within the scrotum. On the right side of the drawing the muscle and connective-tissue layers surrounding the inguinal bursa and testis are shown; on the left side may be seen the loops of the cremaster muscle surrounding the tunica vaginalis communis.
The amphibia possess a true saccular ovary (fig. 32). It has a cortex and  
germinal epithelium somewhat similar to the compact ovarian variety, but
the area which forms the medulla in the compact ovary is here represented
by a large lymph space. During early development, the amphibian ovary is
a compact structure, but later there is a hollowing out and disappearance of  
the compact medullary portion, and the cortical area remains as a relatively
thin, peripheral region (Burns, ’31; Humphrey, ’29).  


Histologically the vertebrate ovary is composed of two general cellular
groups, namely:


Fig. 7. Diagrammatic representation of the general structural relationship of the parts of the human testis. (Modified from Corner, 1943, after Spalteholz and Huber.)
(1) germ cells, and  


(2) general tissue cells of various kinds, such as epithelium, connective
tissue, smooth muscle fibers, and the complex of elements comprising the vascular system of the ovary (figs. 30, 32). Some of the general
cells form the so-called interstitial tissue of the ovary.


4. Specific Structures of the Mammalian Testis Which Produce THE Reproductive Cells and the Male Sex Hormone
The germ cells differ from the general cells in that each of them has a
latent potency for developing a new individual. This latent condition is converted into active potentiality during the differentiation of the primitive germ
cell into the mature egg or ovum.


Two very essential processes involved in reproduction are the formation of the sex cells or gametes and the elaboration of certain humoral substances, known as sex hormones. Therefore, consideration will be given next to those portions of the testis which produce the sperm cells and the male sex hormone, namely, the seminiferous tubules and the interstitial tissue.
==2. General Structure of the Accessory Reproductive Organs==


a. Seminiferous Tubules
The accessory reproductive structures of the female vertebrate may be
separated into three general types, viz.:


The seminiferous tubules lie in the septula compartments (fig. 7). The word seminiferous is derived from two Latin words: semen, denoting seed, and ferre, which means to bear or to carry. The seminiferous tubule, therefore, is a male “seed-bearing” structure. Within this tubule the male gametes or sperm are formed, at least morphologically. However, the word semen has a broader implication in that it is used generally to denote the entire reproductive fluid or seminal fluid. The seminal fluid is a composite of substances contributed by the seminiferous tubules and various parts of the accessory reproductive tract.
( 1 ) the total absence of or the presence of a pair of short funnel-like
structures which convey the eggs from the peritoneal cavity through


The exact form and relationship of the various seminiferous tubules (tubuli seminiferi) which occupy each testicular compartment have been the object of much study. It is a generally accepted belief at present that the tubules within each testicular lobule are attached at their distal ends; that is, that they anastomose (fig. 7). Some investigators also believe that there may be other anastomoses along the lengths of these very much contorted and twisted structures. Moreover, it appears that the septula or testicular compartmental partitions are not always complete; the seminiferous tubules of one lobule thus have the opportunity to communicate with those of adjacent lobules. The seminiferous tubules of any one lobule join at their proximal ends and empty into a single straight seminiferous tubule. The straight tubules or tubuli recti pass into the mediastinum and join the anastomosing rete tubules of the rete testis.


The convoluted portions of the seminiferous tubules produce the sperm (spermia; spermatozoa). In the human testis, the length of one of these tubules is about 30 to 70 cm. and approximately 150 /a to 250 ix in diameter. Each tubule is circumscribed by a basement membrane of connective tissue and contains two cell types:


( 1 ) supporting or Sertoli cells, and
Fig. 31 . Three-dimensional representation of the bird ovary together with the funnel
portion (infundibulum) of the oviduct. Recently ovulated egg is shown in the process of
engulfment by the infundibulum. Various stages of developing eggs are shown.


(2) spermatogenic cells or spermatogonia (see fig. 8 and Chap. 3).


The cells of Sertoli are relatively long, slender elements placed perpendicularly to the basement membrane to which they firmly adhere. These cells may undergo considerable change in shape, and some observers believe that they may form a syncytium, known as the “Sertolian syncytium.” Others believe them to be distinct elements. It is said that Sertoli cells may round up and form phagocytes which become free from the basement membrane and move, ameba-like, in the lumen of the seminiferous tubule, phagocytizing degenerating sperm cells. However, their main function appears to be associated with the development of sperm during the period when the latter undergo their transformation from the spermatid condition into the adult
Fig. 32. Anterior half of the saccular ovary of Necturus maculosus.  


an opening into the urogenital sinus and thence to the outside as in
cyclostome fishes,


Fig. 8. Semidiagram matic representation of section of cat testis, showing seminiferous tubules and interstitial tissue, particularly the cells of Leydig.
(2) a short sinus-like tube attached to each ovary and to the urogenital
sinus or to a separate body opening as in many teleost fishes (fig.  
28), and  


(3) two elongated oviducal tubes variously modified (figs. 29, 33, 34,
35, 36, 37).


Sperm form. The Sertolian cells thus may act as nursing elements during sperm metamorphosis.
Except in the teleost fishes the cephalic end of each oviduct generally is
open and is placed near the ovary but not united directly with it (figs. 29,
33) although in some species, such as the rat, it is united with an ovarian
capsule (fig. 37). In some vertebrates the anterior orifice of the oviduct may  
be located a considerable distance from the ovary, as in frogs, toads, and
salamanders. In many vertebrates, as in birds and snakes, there is but one
oviduct in the adult.  


The spermatogenic cells or spermatogonia (germinal epithelium of the tubule) lie toward the outer portion of the seminiferous tubule between the various Sertoli elements. As a rule spermatogonia lie apposed against the basement membrane of the tubule (see fig. 8 and Chap. 3).
In some vertebrates the oviduct is an elongated glandular tube, as in certain
urodele amphibia (fig. 33) and in ganoid fishes; in others, such as frogs,
birds or mammals, it is composed of two main parts: ( 1 ) an anterior glandular
structure and (2) a more caudally placed uterine portion. The latter may
unite directly with the cloaca, as in the frog (fig. 38) or by means of a third
portion, the vaginal canal or vagina located between the uterus and the  
cloaca, as in elasmobranch fishes, reptiles, and birds, or between the uterus
and the external urogenital sinus, as in mammals (figs. 35, 36, 37). The
vaginal canal may be single, as in eutherian mammals, or double, as in metatherian mammals (figs. 35, 36). In metatherian (marsupial) mammals it
appears that a third connection with the oviducts is made by the addition
of a birth passageway. This birth canal represents a secondary modification
of a portion of the vaginal canals and associated structures (figs. 34, 35, 114).  
(See Nelsen and Maxwell, ’42.) One of the main functions of the vagina or
vaginal canal is to receive the intromittent organ of the male during copulation.  


b. Interstitial Tissue


The interstitial tissue of the testis is situated between the seminiferous tubules (fig. 8). It consists of a layer of connective tissue applied to the basement membrane of the seminiferous tubule and of many other structures, such as small blood and lymph vessels, connective tissue fibers, connective tissue cells, mast cells, fixed macrophages, etc. The conspicuous elements of this tissue are the so-called interstitial cells or cells of Leydig (fig. 8). In man, cat, dog, etc., the cells of Leydig are relatively large, polyhedral elements, possessing a granular cytoplasm and a large nucleus.
The anterior opening of the oviduct is the ostium tubae abdominale, a  
funnel-shaped aperture generally referred to as the infundibulum. In the  
transport of the egg from the ovary to the oviduct the infundibulum, in
many species, actually engulfs and swallows the egg.  


5. The Testis of Vertebrates in General
The portion of the oviduct anterior to the uterus often is called the convoluted glandular part; it is highly twisted and convoluted in many species.
In amphibians, reptiles, birds, and in some mammals the glandular portion


In the vertebrate group, the testis shows marked variations in shape and size. In many fishes, the testes are irregular, lobular structures, but in other fishes, amphibia, reptiles, birds, and mammals, they assume an ovoid shape. The size of the testis is extremely variable, even in the same species. The testis of the human adult approximates 4 to 5 cm. in length by 3 cm. wide and weighs about 14 to 19 Gm. The testis of the horse averages 11 cm. long by 7 cm. wide with a weight of 30 to 35 Gm., while that of the cat is 1.6 cm. long and 1.1 cm. wide with a weight of 1.5 Gm. In the mud puppy, Necturus, the testis is approximately 3.5 cm. long and 0.8 cm. wide with a weight of 0.3 Gm. The testis of the large bullfrog is 1 .2 cm. by 0.5 cm. with a weight of 0.8 Gm. In comparison to the foregoing, Schulte (’37) gives the weight of each testis of an Indian elephant as two kilograms!


Regardless of size or shape, the presence of seminiferous tubules and interstitial tissue may be observed in all vertebrate testes. In some species the seminiferous tubule is long; in others it is a short, blunt affair. The interstitial cells may be similar to those described above, or they may be small, inconspicuous oval elements.


6. Accessory Reproductive Structures of the Male a. The Reproductive Duct in Forms Utilizing External Fertilization
Fig. 33. Diagrammatic representation of the reproductive structures of female urodele,


The accessory reproductive organs of the vertebrate male are extremely variable in the group as a whole. A relatively simple reproductive duct (or in some no duct at all) is the rule for those forms where fertilization is effected in the external medium. In cyclostome fishes, for example, the reproductive cells are shed into the peritoneal cavity and pass posteriad to emerge externally by means of two abdominal pores. Each pore empties into the urogenital sinus. In teleost fishes (perch, flounder, etc.) the conveying reproductive duct is a short, simple tube continuous with the testis at its caudal end and passing posteriorly to the urogenital sinus (fig. 9A). In frogs and toads, as well as in certain other fishes, such as Amia and Polypterus, the male reproductive duct is a simple, elongated tube associated with the testis by means of the efferent ductules of the latter, coursing posteriad to open into the cloaca (frogs and toads) or to the urogenital sinus (Amia; Polypterus) (fig. 9B, C). Simplicity of sperm duct development and external union of the gametes are associated reproductive phenomena in the vertebrate group.
Necturus maculosus.  


b. The Reproductive Duct in Species Practicing Internal Fertilization


An entirely different, more complex male reproductive duct is found (with some exceptions) in those vertebrates where gametic union occurs within the protective structures of the maternal body. Under these circumstances there may be a tendency for one male to serve several females. Enlargement of the duct with the elaboration of glandular appendages, and structures or areas for sperm storage is the rule under these conditions (fig. 9D--F). This form of the male genital tract is found not only in those species where an intromittent organ deposits the sperm within the female tract, but also where the sperm are deposited externally in the form of spermatophores (fig. 10).
Fig. 34. Diagrammatic lateral view of female reproductive system of the opossum,  
showing pseudo-vaginal birth canal.  


In many species, the reproductive duct is greatly lengthened and becomes a tortuous affair, especially at its anterior or testicular end. In fact, the cephalic end of the duct may be twisted and increased to a length many times longer than the male body itself. This coiled, cephalic portion is called the duct of the epididymis (epididymides, plural). (See figs. 7, 9E.) The word epididymis is derived from two Greek words: epi = upon, and didymis = testicle. The epididymis, therefore, is the body composed of the tortuous epididymal duct and the efferent ducts of the testis which lie upon or are closely associated with the testis. The complex type of reproductive duct is composed thus of two main portions, an anterior, contorted or twisted portion, the epididymal duct, and a less contorted posterior part, the vas deferens or sperm duct proper (fig. 9D, E).


In some vertebrates, in addition to the above complications, the caudal end of the reproductive duct has a pronounced swelling or diverticulum, the seminal vesicle (e.g., certain sharks and certain birds). The latter structures are true seminal vesicles in that they store sperm during the reproductive period.


The epididymal duct in man is a complex, coiled canal composed of a head (caput), a body (corpus), and a tail (cauda). (See fig. 7.) It is C-shaped with its concavity fitting around the dorsal border of the testis, the head portion being located at the anterior end of the latter. The total length of the epididymal duct in man is said to be about 4 to 7 m. In other mammals the epididymal duct may be much longer. For example, in the ram, from 40 to 60 m.; in the boar, 62 to 64 m.; in the stallion, 72 to 86 m. (Asdell, ’46). At its caudal end it becomes much less tortuous and gradually passes into the vas deferens (ductus deferens).
Fig. 35. Reproductive structures of female opossum shown from the ventral view. Observe that the ovary and infundibular portion of the Fallopian tube lie dorsal to the horn
of the uterus.  


functions to secrete an albuminous coating which is applied to the egg during
its passage through this region. In amphibians, reptiles, and birds it forms
the major portion of the oviduct, but in mammals it is much reduced in size
and extent. In the latter group it is referred to as the uterine or Fallopian tube.


The uterus is a muscular, posterior segment of the oviduct. Like the
anterior glandular portion of the oviduct, it also has glandular functions, but
these are subservient to its more particular property of expanding into an
enlarged compartment where the egg or developing embryo may be retained.
The protection and care of the egg or of the embryo during a part or all of
its development, is the main function of the uterus in most vertebrates. In the
frogs and toads, however, this structure seems to be concerned with a “ripening” process of the egg. Large numbers of eggs are stored in the uterine sac
of the frog for a period of time before spawning.


Fig. 9. Various vertebrate testes and reproductive ducts, emphasizing the relative simplicity of the duct where external fertilization is the rule while complexity of the duct is present when internal fertilization is utilized. There are exceptions to this rule, however. (A) Flounder (Limanda ferruginea). (B) Frog (Rana catesbiana). (C) Urodele (Cryptobranchus alleganiensis). (D) Dog shark (Squalus acanthias), (E) Urodele (Necturus rnaculosus). (F) Rooster (G alius domestic us).
Various degrees of union between the uterine segments of the two oviducts are found in mammals. In the primates they fuse to form a single
uterine compartment with two anterior uterine tubes (fig. 29). In carnivores,
there is a caudal body of the uterus with two horns extending forward to
unite with the uterine tubes (fig. 36). In the rat and mouse, the uterine segments may be entirely separate, coming together and joining the single vaginal
chamber (fig. 37). In the opossum the uterine segments are entirely separated,  
joining a dual vaginal canal system posteriorly (figs. 34, 35, 114).  




The ductus deferens has a length of about 30 to 35 cm. in man. Leaving the scrotum it passes anteriad together with accompanying nerves and blood vessels in the subcutaneous tissue over the front of the pelvic bone into the peritoneal cavity through the inguinal ring (fig. 2). Here it separates from the other constituents of the spermatic cord (i.e., it separates from the nerves and blood vessels) and passes close to the dorsal aspect of the bladder and dorsally to the ureter. It then turns posteriad along the dorsal aspect of the neck of the bladder and the medial region of the ureter, and accompanied by its fellow duct from the other side, it travels toward the prostate gland and the urethra. Just before it enters into the substance of the prostate, it receives the duct of the seminal vesicle. The segment of the vas deferens from the ureter to the seminal vesicle is considerably enlarged and is called the ampulla. After receiving the duct of the seminal vesicle, the vas deferens becomes straightened and highly muscularized — as such it is known as the ejaculatory duct. The latter pierces the prostate gland located at the caudal end of the bladder and enters the prostatic portion of the urethra; from this point the urethra conveys the genital products.
==D. Dependency of the Female Reproductive System on General Body==


Conditions


The auxiliary glands associated with the genital ducts of the human male consist of the seminal vesicles, the prostate gland, Cowper’s glands, and the glands of Littre.
1. Inanition


In the immature female mammal continued underfeeding results in general
retardation of sexual development. The younger follicles may develop, but
the later stages of follicular development are repressed. In the adult female,
inanition produces marked follicular degeneration and atresia as shown by
many records of retarded sexual development, reduced fertility, even cessation
of the cyclic activities of menstruation and estrus occurring in man and
domestic animals during war-produced or natural famine (Mason in Allen,
Danforth, and Doisy, ’39, p. 1153). The ovary thus seems to be especially
susceptible to starvation conditions, even more so than the testis. As the
condition and well-being of the secondary reproductive structures are dependent upon proper ovarian function, this part of the reproductive system
suffers marked changes as a result of ovarian dysfunction during prolonged
starvation.


The seminal vesicles are hollow, somewhat tortuous bodies (fig. 2). Each vesicle arises in the embryo as an outpushing (evagination) of the vas deferens. The prostate gland has numerous excretory ducts which empty into the urethra. It represents a modification of the lining tissue of the urethra near the urinary bladder together with surrounding muscle and connective tissues. Cowper’s (bulbourethral) glands are small pea-shaped structures placed at the base of the penial organ; their ducts empty into the urethra. The glands of Littre are small, glandular outgrowths along the urethra and are closely associated with it.
To summarize the matter relative to the structural conditions of the reproductive duct in the male of those species which practice internal fertilization:
# A lengthening and twisting of the duct occurs.
# A sperm-storage structure is present, either as a specialized portion of the duct or as a sac-like extension.
# Certain auxiliary glands may be present. These glands are sometimes large and vesicular structures, such as the seminal vesicles of the human duct, or they may be small glands distributed along the wall of the duct, such as the glands of Littre.
===C. Specific Activities of the Various Parts of the Male Reproductive System===
1. Introduction


a. Three General Functions of the Male Reproductive System


The activities of the testes and the accessory parts of the male reproductive
Fig. 36. Schematic representation of reproductive organs of the female cat. On the left
system result in the performance of three general functions as follows:
side of the illustration, the body of the uterus and uterine horn have been cut open, and
the Fallopian tube and ovary are highly schematized. Observe the partial ovarian capsule
around the ovary shown on the right and the relatively fixed condition of the infundibular
opening of the oviduct lateral to the ovary.


# formation of the semen,
# delivery of the semen to the proper place where the sperm may be utilized in the process of fertilization, and
# elaboration of the male sex hormone.




b. Some Definitions


Semen or seminal fluid is the all-important substance which the male contributes during the reproductive event. It is the product of the entire reproductive system, including special glands of the accessory reproductive structures. The semen is composed of two parts:
Fig. 37. Diagrammatic representation of the reproductive organs of the female rat,
showing the bursa ovarica around each ovary. Observe that uteri open directly into the  
vagina. (Modified from Turner, ’48.)


(1) The sperm (spermatozoa, spermia) are the formed elements which
Fig. 38. Diagrammatic representation of reproductive structures of the female frog.
take part in the actual process of fertilization.  
Observe that the ostium of the oviduct is not an open, mouth-like structure. It remains
constricted until the egg starts to pass through.  


(2) The seminal plasma, a fluid part, is a lymph-like substance containing various substances dissolved or mixed in it. These contained substances are important as a protection for the sperm and as an aid to
the process of fertilization.


With regard to the second function of the male genital system, namely,
2. Vitamins
the delivery of sperm to the site of fertilization, it should be observed that


a. Vitamin A


The ovary is not immediately sensitive to a lack in vitamin A in the diet
but general epithelial changes in the reproductive tract occur which may aid
in producing sterility (Mason, ’39).


Fig. 10. Spermatophores of common urodeles. (Redrawn from Noble: Biology of the
b. Vitamin B  
Amphibia, New York, McGraw-Hill.) (A) Triturus viridescens. (After Smith.) (B)
Desmognathus fuscus, (After Noble and Weber.) (C) Eiirycea hislineata.


Ovarian and uterine atrophy occur as a result of deficiency of this vitamin
in monkey, rabbit, mouse and rat (Mason, ’39). This effect may be mediated,
at least partly, through the effect of B-deficiency upon the pituitary gland.


in some vertebrates this is a more simple problem than in others. In those
c. Vitamin C
forms which practice external fertilization, the male system simply discharges
the seminal fluid into the surrounding external medium. However, in those
vertebrates where internal fertilization is the rule, the female system assumes
some of the burden in the transport of the semen to the region where fertilization is consummated, thus complicating the procedure. In these instances,
the male genital tract is called upon to produce added substances to the seminal
fluid which aid in protecting the sperm en route to the fertilization site.  


The elaboration of the androgenic or male sex hormone is a most important function. Androgenic or male sex hormone substances are those organic
During the earlier stages reproductive activity is maintained, but advanced
compounds which induce maleness, for they aid the development of the male
stages of C-deficiency produce regressive effects (Mason, ’39).  
secondary sex characteristics, enhance the growth and functional development
of the male accessory reproductive structures, and stimulate certain aspects
of spermatogenesis.' Like the estrogens, androgens are not confined to a
particular sex; they have been extracted from the urine of women and other
female animals. The androgens derived from urinary concentrates are androsterone and dehydroisoandrosterone. These two androgens are not as powerful
as that prepared from testicular tissue. Testicular androgen was first isolated
from testicular tissue in 1935 and was given the name testosterone. It also
has been synthesized from cholesterol. It is the most powerful of the androgens
and probably similar, if not identical, with the substance produced in the
testis (Koch, ’42).  




2. Activities of the Testis


a. Seasonal and N on-seasonal Types of Testicular Activity
d. Vitamin E


The testis has two main functions: the production of sperm and formation
E-deficiency in the female rat does not upset the ovarian and general reproductive behavior. However, established pregnancies are disturbed and are
of the male sex hormone. In many vertebrates these two activities represent
terminated by resorption of the embryo (Mason, ’39). In the domestic fowl,
a continuous procedure during the reproductive life of the male animal. This
unless sufficient amount of vitamin E is present in the egg, embryonic death
occurs during early incubation periods of the egg.  


3. The Hypophysis (Pituitary Gland)


The ovaries experience pronounced atrophy as a result of hypophysectomy
in mammals and non-mammalian species. The earlier stages of follicle formation in the higher mammalian ovary up to the stage of beginning antrum
formation are not so much affected, but later follicular development and interstitial tissue growth are inhibited (Smith, P. E., ’39). (See fig. 40.)


Fig. II. Seasonal spermatogenesis and accessory gland development in the ground
==E. Activities of the Ovary in Producing the Reproductive State==
squirrel, Citellus tridecemlineatus. Stippling below base line shows period of hibernation,
whereas crosshatching reveals the reproductive period. (From Turner: General Endocrinology, Philadelphia, Saunders, after L, J. Wells.)


condition is found in certain tropical fish, in the common fowl and various
===1. The Ovary as a "Storehouse"of Oogonia===
wild tropical birds, and in many mammals, such as man, the dog, bull, stallion,
cat, etc. On the other hand, in the majority of vertebrates these activities of
the testis are a seasonal affair. This condition is found in most fish, practically
all amphibia, all temperate -zone-inhabiting reptiles, most birds, and many
mammals. Among the latter, for example, are the ferret, deer, elk, fox, wolf,
and many rodents, such as the midwestern ground squirrel. Seasonal periodicity
is true also of the common goose and turkey.


Sperm-producing periodicity is not correlated with any particular season,
The cortex of the ovary contains many young ova in various stages of development. In the human ovary shortly after birth, the number of oogonia
nor is spermatogenesis always synchronized with the mating urge, which in  
in the cortex of each ovary has been estimated to reach a number as high
turn is dependent upon the male sex hormone. In some forms, these two
as 300,000. This figure should not be taken too literally, as the amount of
testicular functions may actually occur at different seasons of the year, as
variability in the ovary from time to time is great and degeneration of ova
for example, in the three-spined stickleback, Gasterosteus aculeatus (fig. 15).
is a common episode. Haggstrdm (’21 ) estimated that each ovary of a 22-yearold woman contained 200,000 young ova. In the ovaries of young rats, Arai
(See Craig-Bennett, ’31.) In general, it may be stated that sperm are produced
(’20, a and b) estimated that there were on the average around 5,000 ova
during the weeks or months which precede the development of the mating
under 20 /x in diameter.  
instinct. Many species follow this rule. For example, in the bat of the genus
Myotis, sperm are produced during the late spring and summer months, while
mating or copulation takes place during the fall or possibly early the next
spring (Guthrie, ’33). In the common newt, Triturus viridescens, spermatogenesis comes to pass during the warm months of the summer, and sperm
are discharged from the testis into the reproductive ducts during the late fall
and early spring, while copulation is accomplished in the early spring. The
testes in this species are quiescent during the cool winter months. In the
midwestern ground squirrel, Citellus tridecemlineatus, spermatogenesis begins
in November and is marked during February and March (fig. 11). The animal
hibernates away the winter months and emerges the first part of April in a  
breeding condition. Mating occurs in the early spring (Wells, ’35). In the
garter snake, Tharnnophis radix, sperm are produced in the testes in the summer months, stored in the epididymides during the hibernation period in the  
fall and winter, and used for copulation purposes in the spring (Cieslak,
’45). Again, in the Virginia deer, Odocoileus virginianus borealis, studied by
Wislocki (’43), active spermatogenesis is realized during the summer and  
early autumn months, while the mating season or “rut” which results from
the driving power of the male sex hormone, is at its peak in October and
November (fig. 12). In the fox. Bishop (’42) observed spermatogenesis to
begin in the late fall months, while mating is an event of the late winter and
early spring. In April and May the seminiferous tubules again assume an
inactive state (fig. 13). In the common frog, Rana pipiens, spermatogenesis
is present in the summer months and morphogenesis of spermatids into sperm
happens in large numbers during September, October, and November. Sperm
are stored in the testis over the winter, and the mating instinct is awakened
in the early spring (Glass and Rugh, ’44). Following the mating season in
spring and early summer the testis of the teleost, Fundulus heteroclitus, is
depleted of sperm until the next winter and spring (Matthews, ’38).  


As the seasonal type of testicular activity is present in a large number of  
Without entering into the controversy (Chap. 3) relative to the rhythmic
vertebrate species, it seems probable that it represents the more primitive or
origin of germ cells in the ovary, one must accept the conclusion that the
fundamental type of testicular functioning.  
normal ovary has within it at all times during its reproductive life large numbers of oogonia in various stages of development. Thus the ovary, aside from
its other activities, functions as a storehouse and nursery for young oogonia.
Relatively few of these oogonia develop into mature eggs in the mammals.
For example, the reproductive life of the human female occurs from about
the age of 10 or 14 years to about 48 years. If one egg per monthly cycle
is discharged from the ovary which is functional during that cycle, only about
400 eggs would be matured in this way. The number would be less if pregnancies intervened. If one accepts the figures given by Haggstrom, an enormous number of eggs of the human ovary never reach their potential goal.
Similarly, according to Corner (’43): “The most prolific egg producer among
mammals, the sow, might possibly shed a total of 3,000 to 3,500 eggs, allowing ten years of ovarian activity not interrupted by pregnancy, and assuming
the very high average of 20 eggs at each three weekly cycle, but she has vastly
more than this in the ovaries at birth.”


b. Testicular Tissue Concerned with Male Sex-hormone Production


While one cannot rule out the indirect effects which activities of the seminiferous tubules may have upon the functioning of the testis as a whole, including the interstitial tissue, direct experimental evidence and other observations suggest that the interstitial tissue holds the main responsibility for
===2 . Position Occupied by the Primitive Female Germ Cells in the Ovarian Cortex===
the secretion of the male sex hormone, testosterone, or a substance very
closely allied to it. For example, if a testis from an animal possessing a permanent scrotum is removed from the inguinal bursa and placed within the
peritoneal cavity, the seminiferous tubules tend to degenerate, but the interstitial tissue remains. The sex hormone, under these circumstances, continues
to be produced. Again, males having cryptorchid testis (i.e., testes which have
failed in their passage to the scrotum) possess the secondary sex characteristics of normal males but fail to produce sperm cells. Also, it has been demonstrated that the mammalian fetal testis contains the male sex hormone. However, in this fetal condition, the seminiferous tubules are present only in an
undeveloped state, whereas interstitial tissue is well differentiated. It is probable
in this case that the interstitial tissue of the fetal testis responds to the  
luteinizing hormone in the maternal blood.


Within the cortex the definitive germ cells or oogonia are found in or near
the germinal epithelium (figs. 39, 64). Some authors regard the oogonium
as originating from the cells of the germinal epithelium. (See Chap. 3, section
on “germ cell origin.”) The definitive germ cell soon becomes associated
with small epithelial cells (fig. 41). This complex of a germ cell with its
associated epithelial cells is found somewhat deeper in the cortex, within or
below the tunica albuginea. As the oogonium begins to experience the changes
propelling it toward a state of maturity, it is regarded as an oocyte (Chap. 3).


 
Characteristics of the primitive oocyte are:
Fig. 12. Sections of the testis of the deer, Odocoileus virginianus borealis. (After
# an enlargement of the nucleus,
Wislocki.) (A) Seminiferous tubules of deer in June. Observe repressed state of tubules
# changes within the chromatin material of the nucleus pertaining to meiosis (Chap. 3), and  
and absence of sperm. (B) Epididymal duct of same deer. Observe absence of sperm
# a growth and increase in the cytoplasmic substances (fig. 41).  
and smaller diameter of duct compared with (D). (C) Seminiferous tubules of October deer; spermatogenic activity is marked. (D) Epididymal duct, showing well-developed
epididymal tube and presence of many sperm.
 




In hypophysectomized male rats injected with dosages of pure folliclestimulating hormone (FSH) or with small doses of pure luteinizing hormone (LH; ICSH), the seminiferous tubules of the testis respond and spermatogenesis occurs. However, the interstitial tissue remains relatively unstimulated and the accessory structures continue in the atrophic state. If larger
doses of the luteinizing factor are given, the interstitial tissue responds and
the secondary sexual characters are developed, showing a relationship between
interstitial activity and sex-hormone production. (Consult Evans and Simpson
in Pincus and Thimann, ’50, pp. 355, 356.)


From certain species whose reproductive activities are confined to a particular season of the year, there also comes evidence that the interstitial tissue is the site of sex-hormone production. In the behavior of testicular tissue in
Fig. 40. Effects produced by hypophysectomy on the rat ovary and of replacement
the stickleback, Gasterosteus, as shown by van Oordt (’23) and Craig-Bennett
therapy utilizing injections of pituitary gonadotrophins. (After Evans, Simpson, and  
(’31) sperm are produced actively in the seminiferous tubules during one
Penchaez: Symposia of Quantitative Biology, Vol. 5, 1937. The Biological Laboratory,
period of the year when the interstitial tissue is in an undeveloped condition.  
Cold Spring Harbor, L. 1., N. Y.) (A) Ovary of hypophysectomized animal. Observe
The secondary sex characters also are in abeyance at this season of the year.
However, during the months immediately following sperm production, sperm
are stored within the seminiferous tubules and active spermatogenesis is absent.  
When the seminiferous tubules thus have completed their spermatogenic activity, the interstitial tissue begins to increase, followed by a development of
secondary sex characteristics (figs. 14, 15). A similar difference in the rhythm
of development of these two testicular tissues can be shown for many other
vertebrates. All of these suggestive facts thus serve to place the responsibility
for male sex-hormone production upon the interstitial tissue, probably the
cells of Leydig.  


that Graafian follicles are small. They do not proceed further in their development than
the beginning of antral vacuole formation unless replacement therapy is applied. (B)
Ovarian condition of hypophysectomized animal receiving replacement therapy in the
form of injections of the LH (ICSH) gonadotrophic factor of the anterior lobe of the
hypophysis. Interstitial tissue is well developed. (C) Ovarian condition of hypophysectomized animal receiving the FSH gonadotrophic factor. Note follicular growth and antral
vacuole formation; interstitial tissue between the follicles remains somewhat deficient.
(D) Ovarian condition of hypophysectomized animal receiving injections of FSH plus
LH. Corpora lutea are evident (as well as enlarged follicles not shown in the figure).
Interstitial tissue remains deficient.




Fig. 13. Sections of seminiferous tubules of silver fox. (After Bishop.) (A) Regressed state of tubules following breeding season. (B) Tubule from fox during the breeding season, characterized by active spermatogenesis.


Fig. 41. Development of primary condition of the Graafian follicle in the opossum
ovary. (A) Young oocyte with associated epithelial (granulosa) cells which in (B)
have encapsulated the oocyte. (C) Encapsulating granulosa cells have increased in
number and are assuming a cuboidal shape. (D) Fully developed condition of the
primary Graafian follicle. Cf. secondary condition shown in fig. 42.




Fig. 14. Sections of the testis of the stickleback (Gasterosteus pungitius). (Modified
from Moore, ’39, after Van Oordt.) Cf. fig. 13, (A) Spermatogenic activity with many


formed sperm in seminiferous tubules before the mating season, interstitial tissue in
Fig. 42. Secondary conditions of the Graafian follicle in the opossum ovary. Cf. that of the rat ovary in fig. 40.  
abeyance. (B) At mating period. Interstitial tissue well developed, spermatozoa stored
in the tubules with spermatogenic activity absent.  




As these changes are initiated, the associated epithelial cells increase in
number and eventually encapsulate the oocyte (fig. 41B). This complex of
the oocyte with its surrounding layer of follicle cells is known as an egg follicle.


Fig. 15. Seasonal reproductive cycle in the stickleback {Gasterosteus aculeatus). Cf.
===3. Primary, Secondary, and Tertiary Follicles of de Graaf===
fig. 14. Breeding season is indicated by crosshatching below base line. Observe that
spermatogenic activity follows rise of temperature, whereas interstitial-tissue and sexcharacter development occur during ascending period of light. (Redrawn from Turner:
General Endocrinology, Philadelphia, Saunders, modified from Craig-Bennett, 1931.)


In the mammalian ovary the developing egg with its associated cells is
called the Graafian follicle, so named after the Dutch scientist, Reinier de
Graaf (fig. 1), who first described this structure in mammals in 1672-1673.
De Graaf was in error, partly, for he believed that the whole follicular complex was the egg. The mammalian egg as such was first described in 1827 by Karl Ernst von Baer (1792-1876). The following statement is taken from
de Graaf relative to egg follicles.


c. Testicular Control of Body Structure and Function by the Male
We may assert confidently that eggs are found in all kinds of animals, since
Sex Hormone
they may be observed not only in birds, in fishes, both oviparous and viviparous,
but very clearly also in quadrupeds and even in man himself. Since it is known to
everyone that eggs are found in birds and fishes, this needs no investigation; but
also in rabbits, hares, dogs, swine, sheep, cows, and other animals which we have
dissected, those structures similar to vesicles exhibit themselves to the eyes of the
dissectors like the germs of eggs in birds. Occurring in the superficial parts of  
the testicles, they push up the common tunic, and sometimes shine through it, as
if their exit from the testis is impending. (See fig. 48; also Corner, ’43, page 128.)


The mammalian egg with a single layer of epithelial cells surrounding it
is known as a primary Graafian follicle (fig. 41B-D). As the egg and follicle
grow, the number of epithelial cells increase and eventually there are several


1) Sources of the Male Sex Hormone. Testosterone is prepared from testicular extracts. It is the most potent of the androgens and is believed to be
the hormone produced by the testis. The chemical formula of testosterone is:


on


Fig. 43. Tertiary conditions of the Graafian follicle in the opossum ovary. Similar conditions are found in other mammalian ovaries. (A) Follicle in which the antral vacuoles
are beginning to form. (B) This is a follicle in which the antral vacuoles are more
numerous and are beginning to coalesce. (C) Condition of the Graafian follicle in the
opossum ovary approaching maturity. Observe that the antral space is large and is filled
with fluid, the liquor folliculi, while the egg and its surrounding cumulus cells are located
at one end of the follicle. The thecal tissue around the follicle is well developed.


ciu




o


Fig. 44. Cellular wall of the mature Graafian follicle in the opossum.


CHs
layers of epithelial or granulosa cells surrounding the egg. It may now be
regarded as a secondary Graafian follicle (fig. 42 A, B). When a stage is reached
where the granulosa cells form a layer five to seven or more cells in thickness
extending outward from the egg to the forming thecal layers, small antral
vacuoles begin to appear among the granulosa cells. The latter follicle, which
is capable of forming antral vacuoles, may be regarded as a tertiary Graafian
follicle (fig. 43A).


J\J\J
===4. Hormonal Factors Concerned with the Development of Egg Follicles===


The testis, however, is not the only site of androgen formation. As mentioned above, androgens are found in the urine of female animals, castrates,
The ovary with its contained egg follicles is greatly affected by the gonadotrophic hormones produced in the pituitary body. The removal of the pituitary body (hypophysectomy) causes profound regression of the ovary and
etc. It seems probable that the suprarenal (adrenal) cortex may secrete a
accessory reproductive structures. Accordingly, the response of the ovarian
certain androgenic substance, possibly adrenosterone, a weak androgen. Many
tissues to these hormonal substances produced by the hypophysis is responsible
androgens have been synthesized also in the laboratory (Schwenk, ’44).
for development of the Graafian follicle beyond the early tertiary stage. (See
 
fig. 40 A.) The relationships between the pituitary hormones and the ovary
2) Biological Effects of the Male Sex Hormone. The presence of the male
have been studied most intimately in the mammals; the pituitary and eggfollicle relationship in lower vertebrates is more obscure, and probably varies
sex hormone in the male arouses the functional development of the accessory
with the particular group.  
reproductive structures, the secondary sexual characters, and also stimulates
the development of the seminiferous tubules.  


a) Effects upon the Accessory Reproductive Structures. Castration or removal of the testes from an animal possessing a continuous type
a. Effects Produced by the Gonadotrophic Hormones on the Development of the Mammalian Egg Follicle
of testicular activity produces shrinkage, and a general tendency toward atrophy, of the entire accessory reproductive structures. Injection of testosterone
or other androgens under such conditions occasions a resurgence of functional development and enlargement of the accessory structures (fig. 16).
Moreover, continued injections of the androgen will maintain the accessories
in this functional state (Moore, ’42; Dorfman in Pincus and Thimann, ’50).
Similarly, under normal conditions in those vertebrates which possess the
seasonal type of testicular function, the accessory reproductive organs shrink
in size with a loss of functional activity when the testis undergoes regression
during the period immediately following the active season. An enlargement
and acquisition of a normal functional condition of the accessories follows
testicular development as the breeding season again approaches (Bishop, ’42;
Wislocki, ’43; Matthews, ’38; Turner, C. L., ’19). (Compare figs. 12A-D.)


b) Effects upon Secondary Sex Characteristics and Behavior of
The follicle-stimulating hormone, FSH, appears to increase the number
THE Individual. In addition to the primary effects upon the reproductive
of oogonia and to aid the growth and differentiation of the older follicles. It
system itself, the androgens induce many other secondary structures and alterations of the physiology and behavior of the individual. The influence of the
is possible that some of the effects of FSH upon follicular growth are mediated through its ability, together with small amounts of the luteinizing hormone, LH (ICSH), to cause the formation of estrogen or the female sex hormone, although some investigators believe that estrogen production depends mainly upon the action of LH (ICSH). (See Evans and Simpson in
testicular hormone has been demonstrated in all of the vertebrate groups
Pincus and Thimann, ’50, p. 355.) In harmony with the idea that estrogen
from fishes to mammals (Dorfman in Pincus and Thimann, ’50). Examples
is involved in follicular growth there is some evidence which suggests that  
of testosterone stimulation are: the singing and plumage of the male bird;
introduction of estrogens into the peritoneal cavities of fishes and mammals
hair development of certain mammals; the crowing and fighting, together  
results in a stimulation of mitotic activity in the germinal epithelium of the  
with spur, comb, and wattle growth in the rooster. The disagreeable belligerency and positive energy drive of the bull, stallion, or human male may
ovary. It also has been shown that estrogenic substances retard ovarian atrophy
be attributed, largely, to the action of testicular hormone. However, lest we
in hypophysectomized immature rats.  
disparage this aggressive demeanor unduly, it should be recognized that upon
such explosive force rests the preservation of species and races in some instances. As an example, witness that hairy dynamo of the barren northern
tundras, the bull muskox, whose fiery pugnaciousness when the need arises
undoubtedly has been a strong factor in the preservation of this species.  


An excellent example of the effect of testosterone is shown in the development of antlers and change in behavior of the Virginia deer, Odocoileus virginianus borealis (Wislocki, ’43). In the northern climate, the testes and male
When the Graafian follicles of the mammalian ovary reach the proper
accessory organs reach a profound condition of regression in April and May.  
morphological and physiological conditions (i.e., when they reach the tertiary
Growth of the new antlers starts at this time, and during the late summer the  
follicular stage) an increased sensitivity of the follicle cells to FSH occurs.  
antlers grow rapidly and begin to calcify. During the summer, also, the testes
As a result, antral vacuoles filled with fluid appear among the granulosa cells;
develop rapidly, and spermatogenesis results. Loss of the “velvet” covering of  
these eventually coalesce and form the large antral cavity typical of the  
the antlers is experienced during September, and mating is the rule in October
mature Graafian follicle of the mctatherian and eutherian mammal (fig. 43).  
and November. The antlers are shed in midwinter. If the testes are removed
The presence of LH (ICSH) is necessary to augment the action of FSH
after the naked antler condition is reached, the antlers are shed rapidly. Testosterone administered to does or to young males which have been castrated
during the latter part of follicle development. The beneficial action of FSH
induces the development of antlers. The general scheme of antler development  
and LH together in later follicular development is shown by the fact that the  
suggests, possibly, that the testicular hormone acts upon an anterior pituitary
injection of pure FSH alone is incapable of stimulating growth of the follicle
factor, and this activated factor in turn initiates antler growth. Hardening of  
to its full size or to initiate an increased secretion of estrogen. LH aids the
the antlers and loss of velvet results from testosterone stimulation. Loss of  
maturing process of the follicle only when present in very minimal amounts
the antler is synchronized with a decrease in the amount of testosterone in  
during the early stages of follicle development and in larger amounts during
the blood stream, accompanied by the acquisition of a docile, non-belligerent,
the later stages of follicular growth. Large amounts of LH in the earlier phases
more timid behavior.
of the follicle’s development bring about a premature luteinization of the  
 
follicle with ultimate atresia. A proper quantitative balance of these hormones,  
c) Effects upon the Seminiferous Tubules. Testosterone has a stimulating effect upon the seminiferous tubule and sperm formation. This matter
therefore, is necessary, with FSH being in the ascendency during the earlier
is discussed in Chap. 3.
phases of follicle development, followed by increased amounts of LH with
 
decreasing amounts of FSH as the follicle reaches maturity (figs. 22, 53, 59).
d. Seminiferous-tubule Activity and Formation of Sperm
(For references, consult Evans and Simpson, ’50; Turner, ’48.)
See Chap. 3.
 
e. The Seminiferous Tubule as a Sperm-storing Structure
 
See p. 3 1 .
 
3. Role of the Reproductive Duct in Sperm Formation
 
a. Vertebrates Without a Highly Tortuous Epididyrnal Portion of the  
Reproductive Duct
 
In a large number of vertebrates, morphologically developed sperm pass
from the testis through the efferent ductules of the epididymis (vasa efferentia)
to the epididyrnal duct where they remain for varying periods. However, in
many vertebrates the anterior (proximal) portion of the sperm duct does not
form a tortuous epididyrnal structure similar to that found in other vertebrates. This condition is present in the common frog, Rana; in the hellbender,
Cryptobranchus; in the bowfin, Amia; etc. Because of this fact, the sperm
pass directly into the vas deferens or sperm duct (Wolffian duct) without
undergoing a sojourn through a convoluted epididyrnal portion of the duct.  
 
Correlated with the type of testis and sperm-duct relationship in the frog,  
is the fact that one may obtain viable, fertilizing sperm directly from the
testis. For example, if one removes the testis from a living frog and macerates
it in pond water or in an appropriate saline solution, active sperm are obtained
which are capable of fertilizing eggs in a normal manner. That is, the frog
testis matures sperm morphologically and physiologically. This type of testicular maturation is characteristic of many of the lower vertebrates possessing
simple reproductive ducts.  


h. Stimulating Effects of the Pituitary Gonadotrophins on the Ovaries of Other Vertebrates


The hormonal control of the developing follicle of other vertebrate ovaries
follows similar principles to those outlined above for the mammalian ovary,
although data obtained from studies upon other vertebrates in no way compares with the large quantity of information obtained in mammalian studies.
In the hen, FSH and LH injected together cause a rapid development of the
follicles and premature discharge of the egg from the ovary (Fraps, Olsen,
and Neher, ’42). However, in the pigeon. Riddle (’38) reports that another
pituitary hormone, prolactin, appears to decrease the production of these
hormones and stops egg production with a subsequent atrophy of the ovary.
This may be a special means which reduces the number of eggs laid at each
nesting period. In regard to accessory reproductive structures, an estrogenic
hormone is produced in the ovary of the hen which has profound stimulating effects upon the growth of the oviduct (Romanoff and Romanoff, ’49, pp.
242-244). In the frog, Rana pipiens, mammalian pituitary gonadotrophins
are able to effect ovulation (Wright and Hisaw, ’46). Pituitary gonadotrophins
have been shown also to have profound stimulative effects on the ovaries of
fishes, salamanders, and reptiles.


Fig. 16. Effects of the male sex hormone upon the functional development of the
===5. Structure of the Vertebrate, Mature Egg Follicle===
accessory reproductive structures of the male rat. (After Turner: General Endocrinology ,
Philadelphia, Saunders, p. 324.) (A) Normal male rat condition produced by injection of crystalline male sex hormone for 20 days into castrate before autopsy. (B) Castrated
male litter mate of (A) receiving no replacement therapy.
 
 
Fig. 17. Diagrammatic drawings of the two types of testicular-reproductive relationships occurring in the vertebrate group. (A) Simplified type of reproductive duct connected with the testis by means of efferent ductules. The duct-testis relationship of many
telepst fishes is similar to this but does not possess the efferent ductules, the sinus-like
reproductive duct being attached directly to the testis. Sperm cells (spermatozoa) are
matured and stored within the testis. This type of relationship generally is found where
fertilization is external or where sperm are discharged all at once during a short reproductive period. (B) More complicated variety of reproductive duct, connected with the
testis by means of efferent ducts, but possessing an anterior twisted portion, the epididymal
duct in which the sperm are stored and physiologically matured. This type of duct
generally is found in those vertebrates which utilize internal fertilization and where
sperm are discharged over a short or extended reproductive period.


As a result of the differentiation and growth induced by the gonadotrophic
hormones of the anterior lobe of the hypophysis described in the preceding
paragraphs, the egg follicle reaches a state of maturity (fig. 43C). This state
is achieved when the follicle is about to rupture with the resultant discharge
of the egg. The size of the mature egg follicle varies greatly in different metatherian and eutherian mammals, although the size of the follicle is not related
to the size of the egg. On the other hand the size of the mature egg follicle
in prototherian mammals and in other vertebrate species shows great divergences, being dependent in this group upon the size of the egg at the time
of ovulation (fig. 46).


a. Structure of the Mature Follicle in Metatherian and Eutherian
Mammals"'^


b. The Epididymis as a Sperm-ripening Structure
The structural pattern of the mature Graafian follicle in the human is
strikingly similar to the follicles in other members of this group. It is a vesicular
structure with a diameter approximating five millimeters. Externally, the follicle is composed of two connective-tissue layers, an inner cellular layer containing blood capillaries, the theca interna, and an external, fibrous layer,
the theca externa (figs. 43C, 44). These two layers are not clearly separable.
Passing inward from the theca interna is the basement membrane. Resting
upon this membrane are several layers of epithelial cells comprising the
membrana granulosa. The latter membrane borders the cavity or antrum of
the follicle, which is filled with the liquor folliculi. This liquid is under considerable pressure in the follicle at the time of egg discharge or ovulation.


On the other hand, in those forms which possess an anterior convoluted
Projecting inward into the antrum on one side is a small, mound-like
epididymal portion of the reproductive duct, the journey of the sperm through
mass of granulosa cells, the cumulus oophorus (fig. 43C). Within this hillock
this portion of the duct appears to be necessary in order that fertilizable sperm
of epithelium, is the egg, which measures in the human about 130 /x to 140 fx
may be produced. In mammals it has been shown that the epididymal journey
in diameter. In the opossum, the fully developed Graafian follicle is about
somehow conditions the physiological ripening of the sperm. Sperm taken from the mammalian testis will not fertilize; those from the caudal portion
1.25 by 2 mm. in diameter, while the slightly oval egg approximates 120 by
of the epididymis will, provided they have been in the epididymis long enough.  
135 ii. The egg of the rat and mouse is small, having a diameter of 75 ju,  
Under normal conditions sperm pass through the epididymis slowly, and retain
while that of the dog is about 140 /x; sow, 120 to 140 /x; rabbit, 120 to 130 /x;
their viability after many days’ residence in this structure. Sperm prove to be
monkey, 110 to 120 /x; deer, 115 /x; cat, 120 to 130 (x\ mare, 135 /x; armadillo, 80 /X (Hartman, ’29).  
fertile in the rabbit epididymis up to about the thirty-eighth day; if kept
somewhat longer than this, they become senile and lose the ability to fertilize,
although morphologically they may seem to be normal (Hammond and Asdell,
’26). In the rat, they may live up to 20 to 30 days in the epididymis and still
be capable of fertilization (Moore, ’28). It has been estimated that the epididymal journey in the guinea pig consumes about two weeks, although they
may live and retain their fertilizing power as long as 30 days in epididymides
which have been isolated by constriction (Moore and McGee, ’28; Young,  
’31; Young, ’31b). It is said that in the bull, sperm within the epididymis
may live and be motile for two months. As a result of these facts, it may be
concluded that the epididymal journey normally is a slow process, and that
it is beneficial for the development of sperm “ripeness” or ability to fertilize.  


c. The Epididymis and Vas Deferens as Sperm-storage Organs
* According to Strauss, ’39, the mature Graafian follicle of Erkulus is not a vesicular
structure, as in other higher mammals, but is filled with a loose meshwork of granulosa
cells.  


Along with the maturing faculty, the epididymal duct and vas deferens also
act as sperm-storage organs. As observed on p. 23, in the bat, Myotis, sperm
are formed in great numbers in the seminiferous tubules and pass to the
epididymal duct where they are stored during the fall, winter, and early spring
months; the epididymal journey thus is greatly prolonged in this species. In
the ovoviviparous garter snake, Thamnophis radix, sperm are produced during
the summer months; they pass into the epididymides during early autumn and
are stored there during the fall and winter. In the mammal, sperm are stored
in the epididymal duct.


Aside from its main purpose of transporting sperm to the exterior (see
sperm transport, p. 177), the caudal portion of the sperm duct or vas deferens
also is capable of storing sperm for considerable periods of time. In the
common perch, Perea ftavescens, sperm are developed in the testes in the
autumn, pass gradually into the accessory reproductive ducts, and are stored
there for five or six months until the breeding season the following spring
(Turner, C. L., ’19). Again, in mammals, the ampullary region of the vas
deferens appears to be a site for sperm storage. For example, the ampulla of
the bull sometimes is massaged through the rectal wall to obtain sperm for
artificial insemination. In this form sperm may be stored in the ampulla and
still be viable, for as long as three days. Similarly, in lower vertebrates large
numbers of sperm may be found in the posterior extremities of the vas deferens
during the breeding season. Thus, the reproductive duct (and its epididymal
portion when present) is instrumental in many vertebrate species as a temporary storage place for the sperm.


While one Graafian follicle in only one ovary is generally developed in
the human, monkey, cow, ewe, elephant, etc., at each reproductive period,
a multiple condition is found in many other mammals. Each ovary in the
opossum may ripen seven or more follicles, in the bitch (female dog) from
2 to 7 follicles, and in the sow from 4 to 10 follicles at each reproductive period.


d. Two Types of Vertebrate Testes Relative to Sperm Formation
b. Structure of the Prototherian Egg Follicle


The importance of the epididymal duct in many vertebrates and its relative
The follicle of the prototherian mammals contains a relatively large egg,
absence in others, focuses attention upon the fact that in many vertebrate
while the surrounding fluid and follicular tissue in comparison is small in  
species sperm are produced, stored, and physiologically matured entirely
quantity (fig. 46). In these mammals the egg fills most of the follicular cavity,  
within the confines of the testis (frog, bowfin, stickleback, etc.). The reproductive duct under these circumstances is used mainly for sperm transport.
with the exception of a small fluid-filled space intervening between it and  
In many other vertebrate species sperm are morphologically formed in
the zona pellucida which lies contiguous to the granulosa cells. Internal and  
the testis and then are passed on into the accessory structures for storage and
external thecal tissues surround the granulosa cells as in the Graafian follicle
physiological maturation. Functionally, therefore, two types of testes and two
of the higher mammals.  
types of accessory reproductive ducts are found among the vertebrate group
of animals (fig. 17). It naturally follows that the testis which produces, stores,
and physiologically matures sperm is best adapted for seasonal activity, particularly where one female is served during the reproductive activities. That
is, it functions as an “all at one time” spawning mechanism. On the other hand,
that testis which produces sperm morphologically and passes them on to a
tortuous epididymal duct for storage and physiological maturing is best adapted
for the continuous type of sperm production or for the service of several
females during a single seasonal period. The sperm, under these conditions,
pass slowly through the epididymal duct, and, therefore, may be discharged
intermittently.  


4. Function of the Seminal Vesicles (Vesicular Glands)
c. Egg Follicles of Other Vertebrates


The seminal vesicles show much diversity in their distribution among various mammals. Forms like the cat, dog, opossum, rabbit, sloth, armadillo, whale,
The fully-developed egg follicle in most vertebrates is similar to that found
do not possess them, while in man, rat, elephant, mouse, they are welldeveloped structures. It was formerly thought that the seminal vesicles in  
in the prototherian mammals in that the egg tends to fill the entire follicle.  
mammals acted as a storehouse for the sperm, hence the name. In reality
The general structural relationships also are similar (figs. 45, 47).  
they are glandular structures which add their contents to the seminal fluid
during the sexual act.  


5. Function of the Prostate Gland
===6. Ovulatory Process; Possible Factors Controlling Ovulation===


The prostate gland also is a variable structure and is found entirely in the
The following description of the ovulatory process in the mammal and in  
marsupial and eutherian mammals. In marsupials it is confined to the prostatic portion of the urethral wall; in man it is a rounded, bulbous structure
other vertebrates should not be construed as a description of the mechanism,  
which surrounds the urethra close to the urinary bladder. In many other
as the exact mechanism is unknown. However, a certain amount of general
mammals it is a much smaller and less conspicuous structure. It discharges
information has been obtained concerning ovulation and the factors involved.  
its contents into the seminal fluid during the orgasm. It is probable that the
Much of this information has been obtained from studies of the ovulatory
prostatic and vesicular fluids form the so-called “vaginal plug’’ in the vagina
of the rat, mouse, etc.


6. Bulbourethral (Cowper’s) Glands


The bulbourethral glands are absent in the dog but present in most other
mammals. In marsupials and monotremes these structures are exceptionally
well formed. In the opossum there are three pairs of bulbourethral glands.
The mucous contents of these and other small urethral glands are discharged
at the beginning of the sexual climax and, as such, become part of the seminal fluid.


Fig. 45. (A) Young egg follicle of Cryptobranchus alleganiensis, a urodele. (From
Noble: “Biology of the Amphibia,” New York, McGraw-Hill, after Smith.) (B) Diagrammatic representation of ovarian events in the frog resulting in egg discharge. (From Turner: “General Endocrinology,” Philadelphia, W. B. Saunders, slightly modified.)


7. Functions of Seminal Fluid
a. Amount of Seminal Fluid Discharged and Its General Functions


As stated previously, the semen or seminal fluid is composed of two parts,
Fig. 46. Diagrammatic representation of the egg of the prototherian mammal. Echidna.  
the sperm cells (spermia; spermatozoa) and the seminal plasma. The presence
of the sperm cells represents the most constant feature, although they may
vary considerably from species to species in size, shape, structure, and number
present. The seminal plasma varies greatly as to composition and amount
discharged.  


The quantity of seminal fluid discharged per ejaculate and the relative
numbers of sperm present in man and a few other vertebrate species associated with him are as follows:*




Species
Fig. 47. Diagrammatic drawings of the pendent egg follicle in the ovary of the hen.
(A) Low magnification of the entire egg follicle. (B) More detailed view of the blastodisc portion of the egg, nearing maturity, in relation to the pedicle. The latter supports
the follicle and permits the blood vessels to pass into and out of the follicle. Compiled
from sections of the developing ovary of the hen.


Volume of Single Ejaculate,
Most Common Value, in CC.


Sperm Density in Semen,  
process in higher mammals, especially the rabbit. Among other vertebrates
Average Value, per CC.  
ovulation in the hen and frog have been the objects of considerable study.  


Boar
a. Process of Ovulation in Higher Mammals


250
1) Changing Tissue Conditions Cuhninating in Egg Discharge from the
 
Ovary. As the Graafian follicle enlarges and matures under the influence of the follicle-stimulating and luteinizing hormones, it moves closer to the ovarian
CC.  
surface (fig. 30). The surface of the ovary over the ripening follicle bulges
outward, forming a mound-like protuberance (fig. 30). In the rabbit as shown
by Walton and Hammond (’28) and Hill, Allen, and Cramer (’35) the central part of the original protuberance pushes out still further and forms a
papilla-like swelling (fig. 48A-D). As the papilla develops, it becomes avascuiar, and the underlying tissues become thin and greatly distended. The
tunica albuginea of the ovary and the two thecal layers of the follicle also
are involved in this thinning-out process. As the distended papillary area
continues to grow thinner, a small amount of blood followed by some of the
follicular fluid containing the egg emerges from the follicle and passes into
the surrounding area in close proximity to the infundibulum of the Fallopian
tube (fig. 48 E, F). The entire process is a gradual one and may be described
as gently but not violently explosive (Hill, Allen, and Cramer, ’35). It is of
interest and significance to observe that Burr, Hill, and Allen (’35) were able
to detect a change in electromotive force preceding and during the known
period of ovulation.


100,000,000


per


CC.


Bull
Fig. 48. Process of ovulation in the rabbit. (A-C) Early external changes of the
surface of the ovary overlying the bulging Graafian follicle. (D) Formation of a secondary papilla. (E) Rupture of the secondary papilla with discharge of egg and follicular fluid, the latter oozing down over ovarian surface of the follicle. (F) Area of
rupture with oozing follicular fluid and egg greatly magnified. (G) Follicle after egg
discharge. (A-E and G, slightly modified from Walton and Hammond, Brit. J. Exp.
Biol., 6; F, modifier from Hill, Allen, and Kramer, Anat. Rec., 63.)


4-5


CC.


1,000,000,000
The process of papillary rupture in the rabbit occupies about five seconds;
egg discharge with the surrounding liquor folliculi occurs in approximately
30 to 60 seconds. After the egg has emerged, the follicle as a whole may
collapse. The slit-like opening through which the egg and follicular fluid
passed during ovulation soon is filled with a clot composed of coagulated
blood and follicular fluid (fig. 48G).


per
While the foregoing processes, visible on the ovarian surface, are consummated, certain internal changes occur which form a part of the ovulatory procedure. These changes arc as follows: At about the time the egg is to be
extruded, the follicular fluid reaches its maximum in quantity. This increase
produces considerable follicular turgidity which may be associated with an
endosmotic effect due to an increase in the salt content of the contained fluid.
Shortly before the surface of the follicle ruptures, the cumulus begins to disintegrate, and the egg lies free in the antral fluid. At about this time the first
maturation division of the oocyte occurs in the majority of mammals, and
the first polar body is extruded.


CC.  
Concerning the internal changes accompanying rupture of the mammalian
follicle, passing mention should be made of the theory that bursting blood
vessels discharge their contents into the follicular fluid and thus cause sufficient pressure to rupture the follicle (Heape, ’05). Considerable blood discharge into the follicle seems to be present in some forms, e.g., the mare,
quite absent in others such as the human, and present slightly in the opossum.  


Cock
2) Hormonal Control of the Ovulatory Process. The hormonal mechanism
involved in ovulation in the spontaneously-ovulating mammals probably is as
follows: The follicle-stimulating hormone causes the growth and development
of the follicle or follicles. Estrogen is released by the growing follicles and
possibly by other ovarian tissues due to the presence of small amounts of LH,
and, in consequence, the estrogenic hormone reaches a higher level in the
blood stream (figs. 53; 59).


0.8
In the meantime, it is probable that the corpus luteum hormone, progesterone, is produced in small amounts. The exact source of this hormone is
not clear. It may be produced by old corpora lutea or by the interstitial tissue of the ovary under the influence of luteotrophin, LTH. The presence of
progesterone, in small quantities together with increasing amounts of estrogen, stimulates the anterior lobe to discharge increased amounts of the luteinizing hormone, LH (ICSH). (See figs. 22, 53, 59.) The elevated level of
estrogen, according to this theory also causes a decreased output of FSH until
it reaches a minimal level at the period shortly before egg discharge (figs.
53, 59). As a result, the increased quantity of LH together with FSH has an
added effect upon the follicle which brings about the chain of events leading
to egg discharge. Evans and Simpson in Pincus and Thimann (’50) give the
proportion of 10 parts of FSH to 1 of LH (ICSH) as the proper hormonal
balance in effecting ovulation in the hypophysectomized rat.  


CC.  
In those mammalian species where ovulation is dependent upon the act of
copulation, a nervous stimulus is involved which increases the output from
the pituitary gland of the gonadotrophic factors, particularly LH.  


3,500,000,000
b. Ovulation in Vertebrate Groups Other Than the Higher Mammals


per
The physical mechanism involved in the ovulatory procedure in the lower
vertebrate classes is different from that found in higher mammals. Two forms,
the hen and the frog, have been studied in detail. These two animals represent
somewhat different types of ovulatory behavior.


CC.  
1) Hen. As the hen’s egg develops in the ovary, it gradually pushes the
 
ovarian surface outward; it ultimately becomes suspended from the general
Dog
surface of the ovary by means of a narrowing stalk, the pedicle (figs. 31, 47).
When the ovulatory changes are initiated, the musculature of the ovarian
wall overlying the outer surface of the egg appears to contract, and an elongated narrow area along this outer surface becomes avascular. This avascular
area represents the place where the ovarian surface eventually ruptures to
permit the egg to leave the ovary; it is called variously, the rupture area,
stigma, or cicatrix. Gradually, the cicatrix widens and finally a slit-like opening is formed by a tearing apart of tissues in the central region of the cicatrix.
Contractions of the smooth muscle fibers appear to be responsible for this
tearing procedure (Phillips and Warren, ’37). The egg eventually is expelled
through the opening and in many instances it rolls into the infundibular funnel
of the oviduct which at this time is actively engaged in an endeavor to engulf
or “swallow” the egg (fig. 31).


6
2) Frog. The egg of the frog projects into the ovarian cavity within the
ovary and is attached to the ovarian wall by means of a broad area or stalk
(fig. 45B). As the egg enlarges, it tends to push the ovarian surface outward,
and the egg and its follicle thus forms a mound-like protuberance from the
ovarian surface (figs. 45A, B; 72F). The egg and the surrounding ovarian
tissue thus lies exposed on one aspect to the outer surface of the ovary. The
outer surface of exposure is the stigma or area of rupture, and in the older
follicles this area does not contain blood vessels (fig. 72F). As ovulation
approaches, an opening suddenly appears in the area of rupture. The musculature within the theca interna around the follicle then contracts, and the
egg rolls out through the opening in the rupture area like a big ameba (fig.
45B). As the egg passes through the aperture, it may assume an hourglass
shape (Smith, B. G., T6). After the egg is discharged, the follicle contracts
to a much smaller size (fig. 45B). It has been suggested that the rupture of
the external surface of the follicle might be produced by a digestive enzyme
(Rugh, ’35, a and b).


CC.  
3) Hormonal Control of Ovulation in Lower Vertebrates. The hormonal
 
mechanism regulating ovarian rupture and egg discharge in the lower vertebrate groups has not been as thoroughly explored in all of the vertebrate
200,000,000
groups as it has in the mammals. However, sufficient work has been done to
 
demonstrate that pituitary hormones are responsible in all of the major vertebrate groups, including the fishes. Amphibian pituitary implants under the
per
skin or macerated anterior-lobe pituitary tissue injected into the peritoneal
cavity of various amphibia have been effective in producing ovulatory phenomena (Rugh, ’35a). More recently, purified mammalian follicle-stimulating
hormone, FSH, and luteinizing hormone, LH, have been used to stimulate
egg discharge in frog ovarian fragments, as well as in normal and hypophysectomized females. However, the follicle-stimulating hormone alone will not
elicit ovulation (Wright, ’45; Wright and Hisaw, ’46). Accordingly, both
factors are necessary in the frog, as in mammals. In the hen, these two pituitary hormones have been shown to bring about ovulation when injected
intravenously (Fraps, Olsen, and Ncher, ’42; Romanoff and Romanoff, ’49,
pp. 208-215). Also, Neher and Fraps (’50) present evidence which suggests
that progesterone plays a part in the physiological chain which elicits ovulation
in the hen. A close relationship between the physiological procedures effecting
ovulation in the hen and the mammal thus appears to exist.


CC.  
c. Comparison of the Immediate Factors Effecting Egg Discharge in the


Man
Vertebrate Group


3.5
In the vertebrates thus far studied contraction of muscle tissue of the follicle following the rupture of surface tissues presumably is the main factor
which brings about egg expulsion. In higher mammals, associated with muscle
contracture, there also may be an increase in follicular turgidity due to endosmotic phenomena associated with the contained follicular fluid (Walton and
Hammond, ’28). In the frog, hen, and mammal the changes involved in the
surface tissues leading to their rupture are associated with the following sequence of events:


CC.
( 1 ) avascularity of the surface tissues,


100,000,000
(2) a thinning of the surface tissues, and finally


per
(3) a rupture of these tissues.


CC.  
===7. Internal Conditions of the Ovary as an Ovulatory Factor===


Rabbit
Internal conditions of the ovary undoubtedly are important in controlling
follicular growth and ovulation. For example, in the Northern fur seal,
Callorhinus ur sinus, the female begins to breed at the age of two years. These
seals travel north once a year to the Pribilof Islands in the Bering Sea where
they go on land to give birth to the single young and also to breed. Most of
the cows arrive between the middle of June and the middle of July. Heavy
with young, the females give birth to their offspring within a few hours or
days after their arrival. Breeding again takes place about six days after parturition. However, lactation continues, and the young are taken care of during
the summer months.


1
Accordingly, these seals mate each year and it appears that for any particular year the mating behavior and ovulation of the egg are controlled by
the ovary, which does not have a corpus luteum. As the corpus luteum, which
forms after ovulation in the site of the Graafian follicle, from which the egg
is discharged, remains intact for a considerable portion of the year, the ovary
which does not have the corpus luteum develops the Graafian follicle for the
next summer period. The following year the other ovary will function, and
so on, alternating each year (Enders, et al., ’46). Thus, the corpus luteum
appears to function as a suppressor of follicular growth within the ovary in
which it lies. In the human female, one ovary functions to produce an egg
one month, while the following month the other ovary ovulates its single egg.
It is possible that here also the large corpus luteum suppresses follicular growth
within the particular ovary concerned.


CC.  
During gestation, the presence of the corpus luteum and its hormone,
progesterone, suppresses follicle growth and ovulation in most of the mammalian group. (The placenta may be the source of progesterone during the
later phases of pregnancy in forms such as the human.) On the other hand,
in the mare, according to Cole, Howell, and Hart (’31 ), ovulation may occur
during pregnancy. Species differences, therefore, exist relative to the control
of ovulation by the corpus luteum and its hormone, progesterone.  


700,000,000
===8. Number of Eggs Produced by Different Vertebrate Ovaries===


per  
The number of eggs produced during the lifetime of the female varies with
the species and is correlated generally with the amount of care given to the
young. In many fishes which experience little or no parental care, enormous
numbers of eggs may be produced, as for example, in the cod where several
millions of eggs are spawned in one season. However, in many of the elasmobranch fishes (i.e., the shark group) the eggs develop within the oviduct,
and the young are born alive. Therefore, only six to a dozen eggs produced
each reproductive period is sufficient to keep the shark species plentiful. In
the hen, where careful breeding and selection have been carried out with a view
to egg production, a good layer will lay from 250 to 300 eggs a year. The deer, moose, fur seal, etc., ovulate one egg per year over a life span of a
few years. As stated previously, the human female might ovulate as many
as 400 eggs in a lifetime. In some species the reproductive life is brief. For
example, in the Pacific salmon (Oncorhynchus) females and males die after
their single spawning season, and a similar demise occurs in the eel (Anguilla).


CC.  
===9. Spontaneous and Dependent Ovulation in the Mammals and in Other Vertebrates===


Ram
Spontaneous ovulation without apparent stimulation from external sources
occurs commonly throughout the vertebrate series. However, dependent ovulation conditioned by psychic or other nervous stimuli also is found extensively. In certain mammals ovulation has been shown to be dependent upon
the stimulus induced by copulation, as, for example, the ferret, mink, rabbit,
cat, shrew, etc. The stimulus, carried through the nervous system, affects in
some way the anterior lobe of the pituitary gland which then produces increased amounts of LH in addition to FSH. These females experience estrus
spontaneously, but later follicle growth and egg discharge are dependent upon
the added stimulation afforded by copulation.


1
The element of nervous stimulation has a fundamental relationship to the
ovulatory phenomena in the vertebrates. Dependent ovulation occurs in certain birds, such as the pigeon, where mating provides a psychic or nervous
stimulation which effects ovulation. The presence of two eggs in the nest tends
to suppress ovulation. The removal of these eggs will arouse the ovulatory
procedures. However, the pigeon may sometimes lay eggs without the presence
of a male. In wild birds in general, the mating reaction is linked to the
stimulus for egg laying. The hen, on the other hand, is not dependent upon
copulation, but in many of the domestic varieties the presence of a number
of eggs in the nest appears to suppress egg laying. In the lower vertebrates
nervous stimuli also appear to have an influence upon ovulation. The mating
antics of many fish and amphibia may be connected with ovulatory phenomena.


CC.  
===10. Egg Viability after Discharge from the Ovary===


3,000,000,000
The length of time that the egg may survive and retain its capacity for
 
fertilization after leaving the ovary depends upon the nature of the egg and
per
its membrane and the surrounding environment. In the urochordate, Styela,
 
the egg may remain for 3 to 4 hours after it is discharged into the sea water
CC.  
and still be capable of fertilization. In the elasmobranch fishes, reptiles, and
 
birds the conditions of the oviduct are such that fertilization must take place
Stallion
in the upper part of the oviduct within a few seconds or minutes after the
 
egg reaches the infundibular portion. In Fundulus hetewclitus and possibly
70
many other teleost fishes, the egg must be fertilized within 15 to 20 minutes
 
after spawning. In the frog, the egg passes to the uterus at the lower end of
CC.
the oviduct shortly after it leaves the ovary. Under ordinary reproductive temperatures which obtain in the spring, the egg may remain there for 3 to 5
 
days without producing abnormalities. If kept at very cool temperatures,
120,000,000
the period may be extended. Among the mammals the viability after ovulation
 
varies considerably. In the mare, fertilization must occur within about 2 to 4
per
hours; rabbit, 2 to 4 hours (Hammond and Marshall, ’25); rat, about 10
hours; mouse, 12 to 24 hours (Long, ’12; Charlton, ’17); opossum, probably
within the first hour or so because of the deposition of the albuminous coating
in the oviduct; fox, probably only a few hours; sow, about 24 hours or less;
man, probably 24 hours or less. In the guinea pig, functional degeneration
may begin within 4 to 8 hours after ovulation (Blandau and Young, ’39) .


CC.  
===11. History of the Egg Follicle after Ovulation===
a. Follicles Which Do Not Develop a Post-ovulatory Body


Turkey
The changes which occur within the egg follicle after the egg has departed
are most variable in different vertebrate species. In most of the fish group
the ovary as a whole shrinks to a fraction of its previous size, and many
very small, immature eggs, interstitial tissue, and collapsed, contracted, empty
follicles make up its composition. Similarly, in frogs, toads, and salamanders
the collapsed follicle which follows ovulation does not develop an organized
structure. The thecal tissue contracts into a small rounded form within which
are a few follicle cells (fig. 45B). These bodies soon disappear.


0.3
In many snakes and in turtles, the follicle collapses after ovulation, and it
is questionable whether organized bodies develop in the site of the ovulated
follicle. A similar condition appears to be the case in birds. However, Pearl
and Boring (’18) described an abbreviated form of a corpus luteum in the
hen in both discharged and atretic follicles. Also, Rothschild and Traps (’44)
found that the removal of the recently ruptured follicle or of this follicle together with the oldest maturing follicle, at a time when the egg which originated from the ruptured follicle is in the oviduct, retarded the laying of the
egg from 1 to 7 days. Removal of other portions of the ovary in control
hens “practically never” resulted in egg-laying retardation. The ruptured follicle, therefore, is believed, by these investigators, to have some influence on
the time of lay of the egg. Whether the hormone progesterone or something
similar to it may be produced by the ruptured follicle of the hen is questionable, although present evidence appears to suggest that it does (Neher
and Traps, ’50).  


CC.  
b. Follicles Which Develop a Post-ovulatory Body; Formation of the


7,000,000,000
Corpus Luteum


per
Post-ovulatory bodies or corpora lutea (yellow bodies) develop in the
ovaries of elasmobranch fishes which give birth to their young alive. Also
in viviparous snakes of the genera Natrix, Storeria, and Thamnophis, it has been shown that the removal of the ovaries with their corpora lutea invariably
results in resorption of the young during the first part of gestation and abortion
of the young during the midgestational period, while their removal during
the close of gestation permits normal birth to occur (Clausen, ’40). The
differentiation of the corpus luteum in the snake involves the granulosa cells
of the follicle and possibly the theca interna. The differentiated organ appears
similar to that of the mammal (Rahn, ’39).


CC.  
The function of the corpus luteum which develops in the site of the ruptured follicle in all mammals, including the Prototheria (fig. 49), has been
the subject of a long series of studies. (See Brambell, ’30, Chap. 9; Corner,
’43, Chap. V.) Its function during the reproductive period of the female
mammal is described below under the section of the ovarian hormones.
The events leading to the formation of the corpus luteum in the mammalian
ovary may be described as follows: After the discharge of the egg, the follicle
collapses. The opening of the follicle at the ovarian surface through which
the egg emerged begins to heal. A slight amount of blood may be deposited
within the antrum of the follicle during the ovulation process in some mammals. If so, the follicle in this condition is known as the corpus hemorrhagicum.  




* Modified from Mann (’50).  
Fig. 49. (A) Luteal cells of the corpus luteum of the opossum. The cellular conditions
in other higher mammals are similar. The centsal core has not yet been invaded and resorbed by the phagocytes accompanying the ingrowing luteal cells and blood vessels. This
central core is composed of coagulated blood, blood cells, and connective tissue fibrils.
(B) Corpus luteum of the platypus (Ornithorhynchiis).  




Two important branches of study involving the semen pertain to:
Then, under the influence of the luteinizing hormone, LH, the granulosa cells
of the follicle and also cells from the theca interna, together with blood capillaries, proliferate and grow inward into the antral space (figs. 22, 30, 49).
Phagocytes remove the blood clot within the antral space if present, during
the inward growth of these structures. As the ingression of cells and capillaries into the follicle continues, the granulosa cells begin to form large, polyhedral lutein cells, while the epithelioid cells of the theca interna form a
mass of smaller cells which resemble the true lutein cells; the latter are formed
in the peripheral area of the corpus luteum and are called paralutein cells.
The small spindle-shaped cells of the theca interna, together with blood capillaries, become dispersed between the lutein cells, forming a framework for
the latter.


(1) the chemical and physiological nature and numerical presence of the  
If the egg is fertilized, the corpus luteum persists and is known as the
sperm, and  
corpus luteum of pregnancy; if fertilization does not take place, it is called
the corpus luteum of ovulation. The latter body soon degenerates. Histologically, both types of corpora are identical when first formed. Eventually the  
corpus luteum undergoes involution, and its site becomes infiltrated with
connective tissue. The latter structure is sometimes referred to as the corpus
albicans.


(2) the physiology and biochemistry of the seminal plasma.
===12. Hormones of the Ovary and Their Activities in Effecting the Reproductive Condition===


(See Mann, ’50, for discussion and bibliography.) As a result of the studies
The ovary produces two important hormones which have a profound effect
thus far, a considerable body of information has been accumulated.  
upon the reproductive process. These two hormones are the female sex hormone, estrogen, and the gestational hormone, progesterone.  


The main function of the semen, including the plasma and accessory sperm,
a. Estrogenic Hormone
appears to be to assist the sperm cell whose chance fortune it is to make contact with the egg. Once this association is accomplished, the egg seemingly
takes over the problem of fertilization. The seminal plasma and the accessory
numbers of sperm appear to act as an important protective bodyguard and also as an aid for this event. Modern research emphasizes, therefore, that the
work of the male reproductive system is not complete until this contact is
made.  


1) Definition and Source of Production. The induction of estrus (see p.
93 ) or conditions simulating this state is a property of a relatively large number
of organic compounds. Because of this estrus-inducing power, they are spoken
of as estrogenic substances or estrogens. Estrogens are widely distributed in
nature. Two of the most potent natural estrogens are estradiol and estrone
(theelin). Both have been extracted from the mammalian ovary and are
regarded as primary estrogenic hormones. The most powerful estrogen is
estradiol, and it is regarded at present as the compound secreted by the ovary.
During pregnancy it also is found in the placenta. These structures are not
the only sources of estrogens, however, for it is possible to extract them from
urine after ovariectomy, and they occur in the urine of males as well as that
of females. The urine of the stallion is one of the richest sources of estrogens,
and the testis contains a high estrogenic content (Pincus and Thimann, ’48,
p. 381 ). Estrogens are found also in various plants, such as the potato, pussy
willow, etc.


b. Coagulation of the Semen


In many mammalian species, the semen tends to coagulate after its discharge from the male system. In the mouse, rat, guinea pig, opossum, rhesus
monkey, etc., the semen coagulates into a solid mass, the vaginal plug, once
it reaches the vagina of the female. The probable function of the vaginal
plug is to prevent the semen from seeping out of the vagina. The formation
of this plug may be due to a protein present in the contents of the seminal
vesicle which comes in contact with the enzyme, vesiculase. In the rat and
guinea pig this catalyst probably is produced by the “coagulating gland,” a
specialized structure associated with the seminal vesicles in these forms. Some
of it also may come from the prostate.


Coagulation of the seminal fluid also occurs in man, stallion, and boar but
The structural formulae of estradiol and of estrone are as follows:
it is entirely absent in the dog, bull, and many other animals. Human semen
coagulates immediately after discharge but liquefies a short time afterward.
This liquefaction may be due to the presence of two enzymes, fibrinogenase
and fibrinolysin, found in human semen and both derived from the prostate.
These enzymes are found also in dog semen. In the latter their property of
inhibiting blood coagulation may be of use where considerable amounts of
blood may be present in the female genital tract at the onset of full estrous
conditions. Another important contribution of the prostate gland is citric acid.
Its role is not clear but it may enter into the above coagulation-liquefaction
process (Mann, ’50, p. 348).


OH ()


c. Hyaluronidase


Various enzymes have been demonstrated to be present in the semen of
certain invertebrates and vertebrates. One such enzyme is hyaluronidase which
appears to be produced in the testes of the rat, rabbit, boar, bull, and man.
It is not found in the testes of vertebrates below the mammals. Its specific
function is associated with the dispersal of the follicle cells surrounding the
egg; in so doing it may aid the process of fertilization in mammals.


d. Accessory Sperm
Estradiol Estrone


One sperm normally effects a union with the egg in fertilization. Accessory
sperm may enter large-yolked eggs, but only one is intimately involved in
the union with the egg pronucleus. However, what is meant by accessory
sperm here is the large number of sperm which normally clusters around
the egg during the fertilization process in many animal species. A suggestion
of a function for these accessory sperm follows from the fact that hyaluronidase may be extracted from the semen, presumably from the sperm themselves. Rowlands (’44) and also Leonard and Kurzrok (’46) have shown
that a seminal fluid deficient in sperm numbers may fertilize if hyaluronidase
extracted from sperm (?) is added to such a weakened sperm suspension.
The implication is that the accessory sperm thus may act as “cupbearers”
for the one successful sperm in that they carry hyaluronidase which aids in
liquefying the follicle cells and other gelatinous coating material around the egg.


e. Fructose
2) The Ovary as the Normal Source of Estrogen in the Non-pregnant
 
Female. Aside from the fact that estradiol and estrone are readily extracted
An older concept in embryology maintained that sperm were unable to
from the ovary, certain experiments tend to focus attention on the ovary as
obtain or utilize nourishment after they departed from the testis. More recent
an important site of estrogen production. For example, the removal of the
investigation has shown, however, that sperm do utilize certain sugar materials,  
ovaries of a normal, adult female mammal causes the accessory reproductive
and that their survival depends upon the presence of a simple sugar in the  
organs to undergo profound atrophy. The administration of appropriate
medium in which they are kept. (See Mann, ’50.)  
amounts of estrogen will restore the accessories of such a female to the condition normal for the resting state. (Consult Pincus, ’50, in Pincus and
 
Thimann, Chap. I.) The injection of follicle-stimulating hormone with small
The sugar that is found normally in semen is fructose. It varies in quantity
amounts of the luteinizing hormone into the diestrous (i.e., sexually-resting)
from species to species, being small in amount in the semen of the boar or
female with intact ovaries results in follicular development within the ovaries,  
stallion but considerably larger in quantity in the seminal fluid of the bull,  
accompanied by hypertrophy of the accessory reproductive organs to the full
man, and rabbit. The seat of origin of this sugar appears to be the seminal
estrous condition (Nelsen and White, ’41 ; Pincus, ’50, in Pincus and Thimann) .  
vesicle, at least in man, although the prostate may also be involved, particularly in the rabbit and also in the dog. The dog, however, has but a small
These and similar experiments point to the ovary as the main site of estrogen
amount of fructose in the seminal discharge. The real function of seminal
formation in the body of the non-pregnant female.  
fructose “might be as a readily utilizable store of energy for the survival of
motile spermatozoa” (Mann, ’50, p. 360).  


f. Enzyme-protecting Substances
The exact structures of the ovary responsible for estrogen elaboration are
 
not easily determined. Estrogen is found in all parts of the ovary, but certain
Runnstrom (personal communication) and his co-workers have demonstrated that the fertilizing life of sea-urchin sperm is increased by certain substances found in the jelly coat of the sea-urchin egg. Presumably these
observations and experimental results suggest that it is formed in relation
substances are protein in nature, and, according to Runnstrom, they may
to the follicular tissues and also by the so-called interstitial tissue of the  
act to preserve the enzyme system of the sperm. Similarly, the seminal fluid
ovary. For example, when tumors occur within the thecal tissue of the egg
may act to preserve the enzyme system of the sperm, while en route to the  
follicle in women who have experienced the menopause, there is often an
egg, especially within the female genital tract.
accompanying hypertrophy of the accessory organs. This relationship suggests
 
that thecal gland tissue of the follicle may have the ability to elaborate estrogen (Geist and Spielman, ’43). On the other hand, the normal hypertrophy
===D. Internal and External Factors Influencing Activities of the Testis===
of the granulosa cells of the egg follicle during the normal reproductive cycle,
 
with the presence of follicular fluid containing estrogen in the antral space
Conditions which influence testicular activity are many. Many of the factors are unknown. Nevertheless, a few conditions which govern testis function
of the follicle, points to the granulosa cells as a possible source of estrogen.
have been determined, especially in certain mammalian species. The general
Also, it has been observed that tumorous growths of the granulosa cells of
results of experimental determination of some of the agents which affect
the follicle produce an excess of estrogenic substance (Geist and Spielman,
testicular function are briefly outlined below.
’43). Thus, these observations point to the granulosa cells of the egg follicle
 
of the ovary as being capable of estrogen formation. Another possible source
1. Internal Factors
of estrogen secretion in the ovary is the interstitial cells, derived in part
 
from theca interna tissue and atretic follicles. These cells are large polyhedral
a. Temperature and Anatomical Position of the Testis
epithelioid cells scattered between the follicles. Their growth appears to be
 
directly stimulated by the injection of pure luteinizing hormone (LH; ICSH) in hypophysectomized rats (fig. 40). A rapid production of estrogen results
It is well known that in those mammals which have a permanent scrotal
from such injections and this may mean that these cells are involved in  
residence of the testes failure of the testis or testes to descend properly into the scrotum results in a corresponding failure of the seminiferous tubules
estrogen production within the ovary (Evans and Simpson in Pincus and
to produce sperm. In these instances the testis may appear shriveled and  
Thimann, ’50).  
shrunken (fig. 18). However, such cryptorchid (ectopic) conditions in most
cases retain the ability to produce the sex hormone at least to some degree.
A question therefore arises relative to the factors which inhibit seminiferous
tubule activity within the cryptorchid testis.  
 
The failure of cryptorchid testes to produce viable sperm has been of  
interest for a long time. Observations have demonstrated that the more hidden
 
 
 
Fig. 18. Experimental unilateral cryptorchidism in adult rat. The animal's left testis
was confined within the abdominal cavity for six months, whereas the right testis was
pernfitted to reside in the normal scrotal position. Observe the shrunken condition of the
cryptorchid member. (After Turner: General Endocrinology, Philadelphia, Saunders.)


In the pregnant female mammal the placenta appears to be a source of
estrogen production (Pincus and Thimann, ’48, p. 380; Turner, ’48, p. 422).
This is suggested by the successful extraction of estrogen from the placenta
of the human and the mare and also by the fact that in these females removal
of the ovaries during the middle or latter phase of gestation does not result
in estrogen diminution in urinary excretion.


the testis (i.e., the nearer the peritoneal cavity) the less likely are mature
3) Pituitary Control of Estrogen Formation. The removal of the anterior
sperm to be formed. A testis, in the lower inguinal canal or upper scrotal
lobe of the pituitary gland of the female results in marked atrophy of ovarian
area is more normal in sperm production than one located in the upper
structures (figs. 40, 50) and of the accessory reproductive organs. Replacement therapy (i.e., the injections of the pituitary gonadotrophins, FSH and
inguinal canal or inside the inguinal ring. Studies made upon peritoneal and  
LH) produces a normal reconstitution of the ovarian and reproductive duct
scrotal temperatures of rats, rabbits, guinea pigs, etc., demonstrate a temperature in the scrotum several degrees lower than that which obtains in
tissues, effecting a normal appearance and functioning of these structures
the abdomen. These observations suggest that the higher temperature of the
non-scrotal areas is a definite factor in bringing about seminiferous tubule
injury and failure to produce sperm.


With this temperature factor in mind, Dr. Carl R. Moore (in Allen,
Danforth, and Doisy, ’39) and others performed experiments designed to
test its validity as a controlling influence. They found that confinement alone
of an adult guinea pig testicle in the abdomen led to marked disorganization
of all seminiferous tubules in seven days. After several months of such confinement the seminiferous tubules experience marked degenerative changes
and only Sertoli cells remain (fig. 19A, B). The interstitial tissue, however,
is not greatly impaired. If such a testis is kept not too long within the abnormal
position and once again is returned to the scrotum, spermatogenesis is rejuvenated (fig. 20A, B). In a second experiment, the scrotum of a ram was
encased loosely with insulating material; a rapid degeneration of the seminiferous tubules followed. Young (’27, ’29) in a third type of experiment found
that water 6 to 7° warmer than the body temperature applied to the external
aspect of the guinea-pig testis for a 15-minute period evoked degenerative






Fig. 19. Sections of experimental, cryptorchid, guinea-pig, seminiferous tubules and
Fig. 50. Follicular atresia in guinea pig ovary. (Redrawn from Asdell, ’46.) This atresia
interstitial tissue. (Modified from C. R. Moore in Sex & Internal Secretions, Williams &
is a sporadic but not uncommon event in the normal ovary of the mammal. However,  
Wilkins, Baltimore, 1939.) (A) Testis confined to abdomen for three months. (B)  
after removal of the pituitary gland, marked atresia and degeneration of the more mature
follicles occur. (A) Fragmentation of granulosa cells is shown. (B) Beginning invasion of the antral space by theca interna tissue is depicted. (Cf. fig. 40A.) (C) Late stage of atresia with invasion of the antral space by internal thecal cells.


Testis confined to abdomen for six months. Observe degenerate state of seminiferous
tubule after six months’ confinement. Interstitial tissue not greatly affected by confinement.




changes with temporary sterility (fig. 21). Recovery, however, is the rule in
Fig. 51. Effects of estradiol (estrogen) upon the female genital tract of the opossum.  
the latter instance. Summarizing the effects of such experiments involving
(After Risman, J. Morphol., 81.) (A) Reproductive tract of an ovariectomized female.  
temperature, Moore (in Allen, Danforth, and Doisy, ’39, p. 371) concludes:
“The injury developing from applied heat, although more rapidly effective,
is entirely similar to that induced by the normal body temperature when the
testicle is removed from the scrotum to the abdomen.”


The position of the scrotum and its anatomical structure is such as to
(B) Hypertrophied condition of a female experiencing the normal estrous changes. (C)
enhance its purpose as a regulator of testicular temperature (figs. 2, 6). When
Reproductive tract of an ovariectomized female injected with estradiol (0.9 mm.) 36
the surrounding temperature is cold, the contraction of the dartos muscle
days after the ovaries were removed.  
tissue of the scrotal skin contracts the scrotum as a whole, while the contraction of the cremaster muscle loops pulls the testes and the scrotum closer
to the body, thus conserving the contained heat. When the surrounding temperature is warm, these muscles relax, producing a more pendulous condition
to permit heat loss from the scrotal wall.  


In accordance with the foregoing description of the scrotum as a necessary
thermoregulator for the testis, it has been further shown for those mammals
which possess a scrotum that testis grafts fare much better when transplanted
to the scrotal wall or into the anterior chamber of the eye (Turner, C. D., '48). The anterior chamber of the eyeball possesses a temperature much
cooler than the internal parts of the body.


(fig. 40). This evidence suggests that the pituitary gonadotrophins, FSH and
LH, control the development of the ovary and, through their influence upon
the ovarian tissues, promote the secretion of estrogen with the subsequent
hypertrophy of the female accessory reproductive structures. It is to be observed that it is not at all clear that FSH in pure form is able to elicit estrogen
production without the presence of LH (ICSH). (See Evans and Simpson
in Pincus and Thimann, ’50, p. 355.)


4) Effect of Estrogen upon the Female Mammal. The changes in the
mammalian accessory reproductive organs produced by estrogen are marked.
An increase in vascularity and great hypertrophy of the accessory structures
result from its injection into ovariectomized females. (See figs. 51, 52, 53.)
Increased irritability and activity of the accessory structures also occur. This
increased activity appears to be an important factor in the transportation of
sperm upward within the female accessory organs to the region where the
egg awaits the sperm’s arrival.


The alterations in behavior of the female as a result of estrogen stimulation
may be considerable. Females actually seek the presence of a male during
the period of strong estrogenic influence. The long journey of the female fur
seal to the mating grounds in the Bering Sea, the bellowing and tireless search
of the cow moose, the almost uncontrollable demeanor of seeking the male
on the part of the female dog or of the cow in “heat” — these are a few illustrations of the regnant power of this stimulant upon the female mammal.


Fig. 20. Sections of testis during and after abdominal confinement. (Modified from
C. R. Moore in Sex & Internal Secretions, Williams & Wilkins, Baltimore, 1939.) (A)


Section of left testis to show degenerate state of seminiferous tubules after 24 days of  
The culmination of these changes in behavior, resulting in a receptive attitude
abdominal confinement. (B) Section of right testis 74 days after replacement in scrotum.  
toward the male, is reached at about the time when the egg is discharged
Observe spermatogenic activity in tubules.  
from the ovary in many mammalian species. In certain other mammals the
period of heat may precede the ovulatory phenomena.  


5) Effects of Estrogen in Other Vertebrates. In the hen, estrogenic hormone causes enlargement and functional activity of the oviduct. Estrogenic
substance, when injected into female chicks from the eighteenth to the fortieth
day, causes an enlargement of the oviduct to about 48 times the natural size.
Estrogen also has a profound effect upon the activities of the full-grown hen
and aids in egg production (Romanoff and Romanoff, ’49; Herrick, ’44).
Estrogen has a pronounced effect upon the oviducts of other vertebrate forms.




Fig. 21. Effect of higher temperature applied to external surface of guinea-pig testis.
b. Progesterone - The Hormone of the Corpus Luteum
Water, 47®, was applied to surface of scrotum for period of 10 minutes. Testis was
removed from animal 12 days after treatment. Seminiferous tubules are degenerate.
(Modified from Moore, ’39; see also Young, ’27, J. Exp. Zool., 49.)
 


1) Production of Progesterone. The luteinizing hormone, LH, of the anterior lobe of the pituitary gland is concerned not only with the development of the egg follicle, but also, after ovulation or the discharge of the egg from
the egg follicle, the remaining granulosa cells, and also, some of the theca
interna cells of the follicle are induced by the LH factor to form the corpus
luteum (figs. 30, 49). Corpora lutea also may be induced by estrogens. This,
however, appears to be an indirect stimulus aroused through estrogenic stimulation of the pituitary gland to secrete added amounts of the LH factor (Evans
and Simpson in Pincus and Thimann, ’50, p. 359).


Two types of seminiferous tubules are thus found in mammals. In a few
mammalian species (see p. 6) the temperature of the peritoneal cavity is
favorable to the well-being of the seminiferous tubule; in most mammalian
species, however, a lower temperature is required. On the other hand, the
activities of the interstitial tissue of the testis appear to be much less sensitive
to the surrounding temperature conditions, and the male sex hormone may
be produced when the testes are removed from the scrotum and placed within
the peritoneal cavity.


With regard to the functioning of the testis within the peritoneal cavity
of birds it has been suggested that the air sacs may function to lower the
temperature around the testis (Cowles and Nordstrom, ’46). In the sparrow,
Riley (’37) found that mitotic activity in the testis is greatest during the
early morning hours when the bird is resting and the body temperature is
lower, by 3 or 4° C.


b. Body Nourishment in Relation to Testicular Function
Fig. 52. Characteristic histological changes in the female reproductive tract under the
influence of estrogen and progesterone. (A-C) Vaginal cyclic changes in the rat. In
(A) is shown the condition of the vaginal wall in the diestrus (resting) condition; (B)
shows changes in vaginal wall structure during estrus. Observe cornification of outer layer
of cells; (C) shows vaginal wall tissue immediately following estrus, i.e., during metestrus.
The presence of progesterone tends to suppress the action of estrogen. (After Turner:
General Endocrinology, Philadelphia, Saunders.) (D, E) Cyclic changes of the Fallopian tube of the human female during the reproductive cycle. In (D) is shown the midinterval of the cycle, i.e,, at a time paralleling estrus in mammals in general; (E) shows
the cellular condition of the lining tissue of the Fallopian tube just before menstruation.
In (D) the tissue has responded to the presence of estrogen; (E) effect of progesterone
is shown. (After Maximow and Bloom: A Textbook of Histology, Philadelphia, Saunders.)
(F, G) Cyclic changes in the uterine-wall tissue during the reproductive cycle in the
human female. In (F) is shown general character of the uterine wall during the follicular
phase, i.e., responses to estrogen; (G) shows the general condition of the uterine wall
following ovulation. The uterus is now responding to the presence of progesterone added
to the follicular or estrogenic stimulation. (After Maximow and Bloom: A Textbook of
Histology, Philadelphia, Saunders.)


The testis is a part of, and therefore dependent upon, the well-being of
the body as a whole. However, as observed in the preceding pages the interstitial cells and their activities in the production of the male sex hormone
are less sensitive to the internal environment of the body than are the seminiferous tubules.


The separation of these two phases of testicular function is well demonstrated during starvation and general inanition of the body as a whole. A
falling off of sperm production is a definite result of starvation diets, although
the germinative cells do not readily lose their ability to proliferate even after
prolonged periods of starvation. But the interstitial cells and the cells of
Sertoli are not as readily affected by inadequate diets or moderate starvation
periods. Sex drive may be maintained in a starving animal, while his ability
to produce mature, healthy sperm is lost. On the other hand, long periods
of inanition also affect sex hormone production and the sexual interests of
the animal.


Aside from the abundance of food in a well-rounded dietary regime, adequate supplies of various vitamins have been shown to be essential. Vitamin
A further pituitary principle, however, seems to be involved in the functional behavior of the corpus luteum. This principle, referred to as luteotrophin
Bi is essential to the maintenance of the seminiferous tubules in pigeons.  
(LTH), is associated with the lactogenic-hormone complex produced by the
Pronounced degenerative changes in the seminiferous tubules of rats and
anterior lobe of the pituitary body; it induces the morphologically developed
other mammals occur in the absence of vitamins A and E (Mason, ’39).
corpus luteum to secrete progesterone. (Consult Evans and Simpson in Pincus
Prolonged absence of vitamin E produces an irreparable injury to the testis
and Thimann, ’50, pp. 359, 360; Turner, ’48, p. 379, for references.)
of rats; injury produced by vitamin A deficiency is reparable. The B-complex
of vitamins seems to be especially important for the maintenance of the  
accessory reproductive structures, such as the prostate, seminal vesicles, etc.
The absence of vitamin C has a general body effect, but does not influence the testis directly. Spme of these effects may be mediated through the pituitary
gland. As vitamin D is intimately associated with the mineral metabolism of
the body, it is not easy to demonstrate its direct importance.  


c. The Hypophysis and Its Relation to Testicular Function
The structural formula of progesterone is as follows:


The word “hypophysis” literally means a process extending out below.  
2) Effects of Progesterone. Progesterone reduces the irritability of the accessory structures and stimulates the mucosa of the uterus to undergo further
The early anatomists regarded the hypophysis cerebri as a process of the  
development. This increased developmental and functional condition of the  
brain more or less vestigial in character. It was long regarded as a structure
through which waste materials from the brain filtered out through supposed
openings into the nasal cavity. These wastes were in the form of mucus or
phlegm, hence the name “pituitary,” derived from a Latin word meaning
“mucus.” The word pituitary is often used synonymously with the word
hypophysis.


The hypophysis is made up of the pars anterior or anterior lobe, pars
intermedia or intermediate lobe, and a processus infundibuli or posterior
lobe. The anterior lobe is a structure of great importance to the reproductive
system; its removal (ablation) results in profound atrophic changes throughout the entire reproductive tract.


The importance of the pituitary gland in controlling reproductive phenomena was aroused by the work of Crowe, Cushing, and Homans (TO)
Fig. 53. Relationship of the pituitary gonadotrophins and ovarian hormones to the developing Graafian follicle and reproductive-duct change in a polyestrous female mammal.  
and by Aschner (’12) who successfully removed the hypophysis of young
dogs. One of the first fruits of this work was a demonstration of the lack of
genital development when this organ was removed. Since that time many


the other cohabitants of man — rats, mice, cats, rabbits, etc. — have been
The Graafian follicle responds to the pituitary gonadotrophins, FSH and LH, with the
hypophysectomized, and in all cases a rapid involution and atrophy of the  
subsequent growth and ultimate rupture of the follicle and ovulation. Ovulation terminates the follicular phase of the cycle. Under the influence of the LH factor the corpus
genital structures results from pituitary removal. The testis undergoes profound shrinkage and regression following hypophysectomy, the degree of  
luteum is established. The latter becomes functional as a result of stimulation by the
change* varying with the species. In the rooster and monkey, for example,
luteotrophic (lactogenic) hormone. The progestational hormone (progesterone) then is
regressive changes are more marked than in the rat. (Consult Smith, ’39, for
elaborated by the luteal cells. The activity of the latter together with estrogen controls
data and references.)
the luteal phase of the cycle.  
 
A striking demonstration of the influence of the hypophysis upon the  
genital tract is the result of its removal from a seasonal-breeding species,
such as the ferret. Ablation of the pituitary in this species during the nonbreeding season causes slight if any change in the testis and accessory reproductive organs. However, when it is removed during the breeding season,
a marked regression to a condition similar to that present during the nonbreeding season occurs (Hill and Parkes, ’33).  


The experimental result of hypophysectomy on many animal species thus
The rising level of estrogen in the blood suppresses FSH secretion, and together possibly with small amounts of progesterone stimulates LH secretion. Estrogen and small
points directly to this structure as the site of hormonal secretion, particularly
amounts of progesterone also probably stimulate the secretion of large quantities of LTH,  
to the anterior lobe (Smith, ’39). The initial work on the relation of pituitary
and the latter stimulates the secretion of progesterone from the recently formed corpus
hormones and the gonad was done upon the female animal. The results of  
luteum. When the estrogen level falls, FSH again is secreted.  
these studies aroused the question whether one or two hormones were responsible. The latter alternative was suggested by the work of Aschheim and
Zondek (’27) and Zondek (’30) who concluded that two separate substances
appeared to be concerned with the control of ovarian changes.  


Nevertheless, for a time the concept of only one gonad -con trolling (gonadotrophic) hormone was produced by the pituitary, continued to gain attention, and some workers suggested that the two ovarian elfects of follicular
When the estrogen level rises, the endometrium of the uterus and vaginal mucosa are
growth and luteinization of the follicle were due to the length of time of  
stimulated. The presence of progesterone suppresses vaginal development, but the uterine
administration of one hormone and not to two separate substances. However, this position soon was made untenable by research upon the gonadotrophic substances derived from the pituitary gland. Studies along this line
mucosa is stimulated to greater activity. Observe that the involution of the endometrial
by Fevold, Hisaw, and Leonard (’31) and Fevold and Hisaw (’34) reported
lining in most mammals is gradual but in primates it is precipitous and violent, resulting
the fractionation, from pituitary gland sources, of two gonadotrophic substances, a follicle-stimulating factor or FSH and a luteinization factor or LH.  
in menstruation (Cf. fig. 59). (The diestrous period on this chart is shown as a relatively brief period compared to the other aspects of the reproductive cycle. However,  
This work has been extensively confirmed. It should be observed in passing
it may be very long in females which do not experience a polyestrous condition and in
that the male pituitary gland contains large amounts of FSH, although, as
some species it may last a good portion of a year.) (Compiled from various sources in  
mentioned below, the function of the testis and the male reproductive system
the literature. The portion of the chart showing pituitary and gonadal hormonal relationships is based on data obtained from The Schering Corporation, Bloomfield, N. J.)  
relies to a great extent upon the luteinizing factor. Some investigators refer
to the LH factor as the interstitial-cell-stimulating hormone, ICSH. (See Evans,
’47; and also Evans and Simpson in Pincus and Thimann, ’50.)  


The action of these two hormones upon testicular tissue, according to
present information, is somewhat as follows: If pure follicle-stimulating hormone, FSH, which produces only FSH effects in the female, is injected in
low doses into hypophysectomized male rats, the seminiferous tubules are
stimulated and spermatogenesis occurs. Under these conditions, the interstitial
tissue remains unstimulated and the accessories continue in an atrophic state.
It has further been demonstrated that slight amounts of the luteinizing gonadotrophic hormone, LH (ICSH), added to the above injections of FSH,
effects a much better stimulation of the spermatogonial tissue, and the interstitial tissue also develops well.


On the other hand, when pure LH (ICSH) is given alone in small doses,
accessory reproductive structures added normally to the estrogenic effects
spermatogenesis is stimulated with slight or no effect upon the male accessory  
during the reproductive cycle constitutes the luteal phase of the cycle. In this
structures. However, when larger doses of the LH (ICSH) factor alone are
phase of the cycle the uterine glands elongate and begin secretion, and the  
injected, the interstitial tissue is greatly stimulated, and the testicular weight
uterus as a whole is prepared for gestation as a result of the action of the  
increases much more than when FSH alone is given. Furthermore, the accessory reproductive structures are stimulated and become well developed, suggesting the elaboration of the male sex hormone. In agreement with these
progestational hormone, progesterone, associated with estrogen. (See figs.
results, the administration alone of testosterone, the male sex hormone, increases the weight and development of the accessory structures in hypophysectomized animals and it also maintains spermatogenesis. It appears, therefore, that the effects of the LH substance upon the seminiferous tubules and
53, 59.)
the accessory organs occur by means of its ability to arouse the formation of
the male sex hormone.  


A summary of the actions of the pituitary gonadotrophic hormones upon
==F. Reproductive State and Its Relation to the Reproductive Cycle in Female Vertebrates==
testicular tissue may be stated as follows:


( 1 ) Pure FSH in small doses stimulates the seminiferous tubules and
The changes in the female reproductive organs resulting in structural growth
spermatogenesis with little or no effect upon the interstitial tissue or
and development referred to above (70-74, 85-88) are consummated in the  
the accessory reproductive structures, such as the seminal vesicles or  
ability of the female to fulfill the reproductive functions. The phase of the reproductive events characterized by the ability to reproduce is known as the reproductive climax. This period of culmination remains for a brief period, to be
prostate gland;
followed by recession and involution once again to a resting condition. This
developmental progression to a state of reproductive climax followed by regression to a resting condition constitutes a cycle of changing events. When
conditions again are right, the cycle is repeated. Each of these cyclic periods
is known as a reproductive or sexual cycle (figs. 53-59). The reproductive
life of all female vertebrates is characterized by this series of cyclic changes.


(2) Small doses of pure LH also stimulate spermatogenesis with little
In most vertebrate species, the female experiences one sexual cycle per
or no stimulation of the accessory structures;  
year, which corresponds to the seasonal cycle in the male. However, in various
mammals and in certain birds, such as the domestic hen, several or many
reproductive cycles may occur during the year. The male, under these conditions, is a continuous breeder; that is, he produces sperm continuously throughout the year.


(3) Pure LH (ICSH) in larger doses stimulates the development of the  
1. Sexual Cycle in the Female Mammal
interstitial tissue with the subsequent secretion of the male sex hormone and hypertrophy of the accessory reproductive organs;
a. Characteristics and Phases of the Reproductive Cycle


(4) The male sex hormone in some way aids or stimulates the process
The estrous cycle in mammals is a complex affair composed of a number
of spermatogenesis, suggesting that the action of LH occurs through
of integrated subcycles. The changes occurring in the ovary are called the
the medium of the sex hormone (fig. 22).  
ovarian cycle; the cellular changes in the uterine (Fallopian tube) form a
cycle; the responses in the mammary glands constitute the mammary cycle;
the cyclic events in the uterus make up the uterine cycle, while those in the  
vagina form the vaginal cycle (figs. 53, 54, 57).  


(Consult Evans and Simpson in Pincus and Thimann, ’50, for data and
The entire estrous cycle may be divided by ovarian changes into two main
references; also Turner, C. D., ’48.)
phases: the follicular phase and the luteal phase (fig. 53). The former is under
the immediate influence of the enlarging Graafian follicle, which in turn is
stimulated by the follicle-stimulating and luteinizing hormones of the pituitary
gland, with the subsequent production of estrogen. It is probable that the
luteinizing hormone, LH, is mainly responsible for estrogen secretion. (See
Evans and Simpson in Pincus and Thimann, ’50, p. 355.) The luteal phase on the other hand is controlled by the activities of the corpus luteum, which
has replaced the Graafian follicle under the influence of the luteinizing hormone. The production of progesterone by the corpus luteum is effected as
stated previously by the pituitary hormone, luteotrophin (LTH). Ovulation
is the pivotal point interposed between these two phases. The follicular phase
may occur without ovulation, but the true luteal phase of a normal or fertile
reproductive cycle is dependent upon the ovulatory phenomena. Certain luteal
conditions may be elaborated in an anovulatory cycle, but we are here concerned with the normal events of the fertile reproductive cycle.  


The foregoing results of the action of the FSH and LH upon testicular
The follicular phase includes that portion of the reproductive cycle known
function might suggest that the LH substance alone is essential in the male
as proestrus and a considerable part of estrus. Proestrus is the period of  
animal. However, it should be observed that without the presence of FSH,
rapid follicular growth and elaboration of the estrogenic substance which
LH is not able to maintain the tubules in a strictly normal manner, the  
precedes the period of estrus. Estrogen stimulates developmental changes in  
tubules showing a diminution of size. Also, in extreme atrophic conditions
the cellular structure of the accessory reproductive organs, particularly the  
of the tubules, pure FSH stimulates spermatogenesis better than similar quantities of LH. It is probable that FSH and LH (ICSH) work together to effect
vagina and the uterus (figs. 52, 53). Estrus represents the climax of the follicular phase. As such, it is a period of sexual receptivity of the male, and,
complete normality in the male. This combined effect is known as a synergistic effect. It also is of interest that the injection of small doses of testosterone
in spontaneously ovulating forms, of ovulation. During other periods of the  
propionate into the normal male, with the pituitary gland intact, results in  
cycle the female is indifferent or even antagonistic to the male. The period
inhibition of the seminiferous tubules, probably due to the suppression of  
of estrus is often called period of heat, or period of rut. Estrus is followed
pituitary secretion by the increased atnount of the male sex hormone in the
by pregnancy if mating is allowed and is successful, or, in many species, by
blood. However, high doses, while they likewise inhibit the pituitary, result
a period of pscudopregnancy if mating is not permitted or if the mating is  
in a level of androgen which stimulates the seminiferous tubules directly
sterile (figs. 53-57). In some animals, such as the dog, pseudopregnancy is  
(Ludwig, ’50).  
a prolonged normal event even if mating does not occur, continuing over a
 
period almost as long as that of normal pregnancy (fig. 54). In other animals,  
Aside from the above actions upon testicular tissue by the luteinizing hormone (LH;ICSH) certain other functions of this substance should be mentioned (see fig. 22). One of these is the apparent dependence of the Sertoli
such as the opossum, pseudopregnancy forms but a brief episode.  
cells upon the presence of the interstitial cells (Williams, ’50). Interstitial
tissue behavior and development in turn relies mainly upon LH (ICSH)
(Fevold, ’39; Evans and Simpson in Pincus and Thimann, ’50). As the sperm
are intimately associated with the Sertoli elements during the latter phases
of spermatogenesis in which they transform from the spermatid into the form
of the adult sperm, a very close association and reliance upon the presence
of the luteinizing hormone thus appears to be established in sperm development.  
 
A further study of the LH factor is associated with the maintenance of  
the seminiferous tubules themselves. In aged males, the interstitial tissue and
the seminiferous tubules normally involute and regress with accumulation
of large amounts of connective tissue material. In testicular grafts made into
the rabbit’s ear, Williams (’50) found, when interstitial tissue was present
in the grafts, the seminiferous tubules were more nearly normal; when absent,  
the tubules underwent fibrosis.
 
Another function of the LH substance apparently is concerned with release
of the sperm from the Sertoli cells. De Robertis, et al. (’46), showed that
anterior pituitary hormones possibly cause release of sperm from the Sertoli
cells in the toad by the production of vacuoles and apical destruction of
the cytoplasm of the Sertoli elements. In testicular grafts Williams (’50) accumulated evidence which suggests that vacuoles and secretion droplets in
the Sertoli cells occurred as a result of LH administration. The combined
results of these investigators suggest that sperm release from the Sertoli cell
is dependent, in some way, upon LH (ICSH) activity.
 
A final function is concerned with the physiological maturing of sperm
in the reproductive duct, at least in many vertebrate species. The well-being
of the epididymis and vas deferens is dependent upon the presence of the
male sex hormone (Creep, Fevold, and Hisaw, ’36). As the male sex hormone results from stimulation of the interstitial cells by the interstitial-cellstimulating substance, LH (ICSH), the connection between this substance
and the physiological maturation of the sperm cell is obvious.  


2. External Environmental Factors and Testis Function
Pseudopregnancy is, generally speaking, intermediate in duration between
that of a normal luteal phase of the cycle and that of gestation. In those female
mammals where it does not occur normally, it is aroused by such procedures
as sucking of the nipples, stimulation of the vagina and cervix by the natural
mating process, or by artificially stimulating these structures. In some forms,
such as the rabbit, pseudopregnancy is aroused by mere handling or even by
sight of a male. (For discussion, see Selye, ’48, p. 813.)


As we have seen above, the anterior lobe of the hypophysis acts as the
The general changes of growth and development of the accessory organs
main internal environmental factor controlling the testes and, through them,
which occur during pregnancy and pseudopregnancy are controlled largely
the reproductive ducts. It has been observed also that food, vitamins, and
by the secretions of the corpus luteum. The conditions thus imposed by the
anatomical position of the testis are important influences in regulating testicular function. Furthermore, general physiological conditions such as health
corpus luteum comprise the luteal or progestational phai^e of the cycle (fig. 57).  
or disease have an important bearing upon the gonads (Mills, ’19). All of the above conditions are contained within the body of the organism, and as
such represent organismal conditions.  


In most mammals, if pregnancy does not occur, the ovary and accessory organs again gradually return to the sexually-resting condition known
as diestrus (fig. 53). In man and other primates the changes within the uterus
are not gradual but are precipitous, and most of the endometrial lining, together with considerable amounts of blood, is discharged to the outside (figs.
53, 59). This phenomenon is called menstruation. The causes of menstruation
are largely problematical; it is related to the fall of the level of either or both of the ovarian hormones, progesterone and estrogen. Why certain mammals
should experience violent endometrial changes evident in menstruation and
others a gradual involution and resorption is a question for the future. The
general period of change following estrus in a non-fertile cycle is known as
metestrus (fig. 53). In the rat and mouse, metestrus is short, about one or
two days; in the human and opossum it occupies approximately ten days to
two weeks of the cycle; in the dog, about 40 to 50 days, depending upon
the pseudopregnant conditions experienced in different females. The word
anestrus is applied to a prolonged diestrus or sexual quiescence between two
sexual cycles. However, the involution experienced by the sexual organs in
anestrus is somewhat more profound than that prevailing during a brief
diestrus. The term lactational diestrus is used to refer to the prolonged diestrous condition in forms such as the rat, wherein estrus is suppressed in the
mother while suckling the young.


Fio. 22. Chart showing the effects of the hypophyseal anterior lobe upon the developing gametes. It also suggests the various factors influencing pituitary secretion of the  
The length of the sexual cycle varies with the species. When females of
gonadotrophic hormones, FSH and LH. Observe that the primitive gamete in the cortex
the rat or mouse are kept away from a male, the estrous or sexual cycle will
of the ovary is subjected to the cortical environment and develops into an oocyte, whereas
repeat itself every 4 to 5 days. In the sow it occurs every 17 to 20 days. In
in the medullary or testicular environment it develops into a spermatocyte. Experiments
the opossum there is a prolonged anestrous period during the summer and  
upon sex reversal have demonstrated that the medullary and cortical portions of the
autumn months followed by a polyestrous period during the winter and spring
gonad determine the fate of the germ cell. In the male area or medulla, the germ cell
when the estrous cycle reoccurs about every 28 days. In the human female,  
differentiates in the male direction, while in the cortex, the differentiation is in the
the sexual cycle occupies about 28 days, and there arc probably about ten
direction of the female gamete or oocyte, regardless of the innate sex-chromosome constitution of the primitive germ cell. The fate of the germ cell thus is influenced by four
normal ovulatory cycles in a year. Some human females may have more,  
main sets of factors: (1) Internal and external environmental factors, controlling the
while others experience a slightly smaller number of true ovulatory cycles
secretions of the pituitary body, (2) Fnvironment of the testicular tissue (medulla) and  
per year.  
possible humoral substances produced in this tissue, (3) Environment of the ovarian
tissue (cortex) and possible humoral substances elaborated there, and (4) Secretions of  
the anterior lobe of the pituitary body.  
 
 
 
 
The following question naturally arises: Do factors or conditions external
to the body impinge themselves in such a way as to control pituitary and
gonadal function?
 


a. Light as a Factor
Many mammals have one estrous cycle per year. This condition, known as  
 
monestrus, is true of most wild mammals, such as the deer, wolf, fox, moose,  
Aside from the supply of nutritive substances or the collision of the many
and coyote. In the shrew, mink, and ferret the moncstrous period may be
nervous stimuli with the individual which may arouse or depress the sexual
prolonged if the female is kept away from the male.  
activities, two of the most important obvious external factors are temperature
and light. Research on the reproductive behavior of many animal species,  
during the past twenty years, has shown that both of these factors have great
significance on the reproductive activities of many vertebrate species. Bissonnette (’30, ’32, ’35, a and b) has accumulated evidence which demonstrates
that light is a potent factor in controlling the reproductive behavior of the
European starling (Sturnus vulgaris) and also of the ferret (Putorius vulgaris).  
In the starling, for example, the evidence shows that green wave lengths of
the spectrum inhibit testicular activity, while red rays and white light arouse
the reproductive function (fig. 23). The addition of electric lighting to each
day’s duration produced a total testis size in midwinter which surpassed the
normal condition in the spring. In the ferret artificially increased day length
beginning at the first part of October brings the testis to maximum size and
activity coupled with a normal mating impulse as early as November and
December (fig. 24). Under normal conditions the male ferret is able to breed
only during February and early March,
 
These findings relative to the influence of light on the reproductive periodicity of animals confirm a fact which has been known for a long time,
namely, that seasonal breeders brought from the northern hemisphere to the
southern hemisphere reverse their breeding season. For example, ferrets which
normally breed from spring to summer in the northern hemisphere shift their
breeding habits to the September-February period when moved to the southern
hemisphere. Inasmuch as the hypophysis is instrumental in bringing about
secretion of the gonadotrophic hormones responsible for the testicular activity,
it is highly probable that light coming through the eyes (see Hill and Parkes,
’33) influences the nervous system in some way arousing the hypophysis and
stimulating it to secrete these substances in greater quantity. However, one
must keep in mind the caution given by Bissonnette, that light is not the only
factor conditioning the sexual cycles of ferrets and starlings.
 
While numerous animals, such as the migratory birds, ferret, mare, many
fish, frogs, etc., normally are brought into a breeding condition during the
period of light ascendency, a large number of animals experience a sexual
resurgence only during the time of year when the light of day is regressing
in span. This condition is found in some sheep, goats, buffalo in nature.  


Various types of polyestrous conditions exist. In the female dog, for example, there are two or three estrous periods per year about 4 to 6 months
apart. In the cat there are several cycles about two weeks apart during the
autumn, winter, and spring. In the domestic sheep there is a polyestrous period
from September to February in which the cycles occur about every 17 days,
followed by an anestrous period from early March to September. In the mare
in North America, estrous cycles of about 19 to 23 days occur from March
to August. In South America the breeding season is reversed, corresponding
to the reversed seasonal conditions south of the equator. In England many
mares breed in autumn and winter (Asdell, ’46).


In some mammals estrus may follow immediately after parturition or birth
of the young. This may occur occasionally in the rat. Under normal conditions
in the fur seal, the female lactates and gestates simultaneously. It is not a
common procedure.


It should be observed that there are two aspects of the female reproductive cycle of the mammal relative to fertilization or the bringing together of the
male and female reproductive cell. One aspect is the sexual receptivity of
the female; the other is the time of ovulation of the egg. In most female mammals sexual receptivity and ovulation are intimately associated and occur
spontaneously in the cycle; in others the two events may be separated. In
the former group, the development of “heat” and the maturing of the egg
follicle are closely associated, while in the latter the conditions favoring sexual
receptivity or heat are developed considerably in advance of the maturation
of the follicle, as noted in the table below.


b. Relation of Estrus and Ovulation in Some Common Mammals




1) Spontaneously Ovulating Forms (Sexual Receptivity of Male Occurs at
or near Time of Ovulation):






Fig. 23. Sections of testis of the starling (Sturnus vulgaris), showing the effect of  
Length of Estrus or Period
electric lighting added to the bird’s normal daily duration of light during the autumn.
of Heat
(After Bissonnette, Physiol. Zool., 4.) (A) Inside young control bird — no light added


— kept inside as control for (B) from November 9 to December 13. (B) Inside young
Time of Ovulation


experimental bird, receiving additional light from “25 watt” bulb from November 9 to
Dog
December 13. Total treatment, 34 davs.


True period of heat about
5-10 days in the middle of
a 21 -day estrous period


Variable: 1st day; 2nd day; 5th day;
etc., of true period of heat


Guinea pig


Fig. 24. Sections of testis and epididymis, showing modification of sexual cycle in the
6-1 1 hrs.  
ferret, Putorius vulgaris, by exposure to increasing periods of light. (After Bissonnette,
’35b.) (A) Seminiferous tubules from normal male over 1 year old, made on October


3, no lighting. (B) Epididymis of normal male on October 3, no lighting. (C) Seminiferous tubules of experimental male on November 7, 36 days of added lighting. (D)
Views vary: 1-2 hrs. after heat or
Epididymis of experimental males on Nov Tiber 7, 36 days of added lighting.
estrus begins; 10 hrs. after; at end
of estrus


Man


deer, some fish, etc. Bissonnette (’41) working with goats found that: “Increasing daily light periods from January 25 to April 5 — followed by diminishing periods until July 5, while temperatures remained normal for the seasons,
Receptivity not always related
with four Toggenburg female goats and one male Toggenburg and one Nubian
to cyclic events
female — led to cessation of breeding cycles in February instead of March,
followed by initiation of breeding cycles in May and June instead of September.” In the ewe, Yeates (’47) also found that a change from increasing
daylight to decreasing length of day induced reproductive activity. In a similar
manner. Hoover and Hubbard (’37) were able to modify the sexual cycle
in a variety of brook trout which normally breeds in December to a breeding
season in August.


12-17 days after onset of preceding menstruation; average around
14th day


b. Temperature Influences
Mare


In the case of the animals mentioned above, temperature does not appear
2-11 days; average length 5-6
to be a major factor in inducing reproductive activity. However, in many
days
animals temperature is vitally influential in this respect. For example, in the
thirteen-lined spermophile (ground squirrel) Wells (’35) observed that breeding males kept at 40° F. continued in a breeding condition throughout the
year. Under normal conditions this rodent hibernates during the winter months
and comes forth in the spring ready to breed; sperm proliferation and general
reproductive development take place during the period of hibernation. As
the temperature rises during the spring and summer, testicular atrophy ensues,
followed by a period of spermatogenesis and reproductive activity when the
lowered temperatures of autumn and winter come again. Light, seemingly, is
not a factor in this sexual cycle. Another instance of temperature control
occurs in the sexual phase of the common red newt, Triturus viriciescens. Here
it is the rising temperature of the summer which acts as the inducing agent,
and sperm thus produced are discharged into the accessory ducts during the
fall and winter to be used when copulation occurs in early spring. However,
if this species is kept at a relatively low temperature of 8 to 12° C. during
the summer months, spermatogenesis is inhibited and the testis regresses. In
the stickleback, Gasterosteus aculeatus, as reported by Craig-Bennett (’31),
spermatogenesis occurs during July to early September and appears to be
conditioned by a rising temperature, whereas the interstitial tissue and the
appearance of secondary sexual features reach their greatest development
under increased light conditions and slowly rising temperatures (fig. 15).
Bissonnette, in his work on ferrets, also observed a difference in the behavior
of these two testicular components; the interstitial tissue responds to large
increases of daily light periods, whereas the seminiferous tubules are stimulated by small, gradually increasing periods of light.


The above examples emphasize the importance of a single environmental
About 1-2 days before end of estrus; best breeding about 3 days
factor on the pituitary-gonadal relationship. However, in the hedgehog,
after heat begins
Allanson and Deansley (’34) emphasize temperature, lighting, and hormone
injections as factors modifying the sexual cycles, while Baker and Ransom
(’32, ’33, a and b) show that light, food, temperature, and locality affect
the sexual cycles and breeding habits of the field mouse. In some vertebrates,
therefore, a single factor may be the dominant one, whereas in others, numerous factors control the action of the pituitary and reproductive system.


E. Internal Factors Which May Control Seasonal and Continuous Types
Sheep
of Testicular Function


In endeavoring to explain the differences in response to external environmental factors on the part of seasonal and continuous breeders, one must
About 36 hrs.
keep in mind the following possibilities:


(1) The anterior lobe of the hypophysis in some forms (e.g., ferret)
Late in estrus or just after estrus
cannot be maintained in a secretory condition after it has reached its
climax; that is, it apparently becomes insensitive to the light factor. As a
result, regression of the pituitary and testis occurs (Bissonnette, ’35b).


(2) In the starling, the anterior hypophysis may be maintained by the
lighting, but the testis itself does not respond to the presence of the
hypophyseal hormones in the blood (Bissonnette, ’35b). The possibility in this instance may be that testicular function wanes because
the body rapidly eliminates the hormone in some way (see Bachman,
Collip, and Selye, ’34).


(3) Consideration also must be given to the suggestion that the activities
ends; presumably about 20-36
of the sex gland by the secretion of the sex hormone may suppress
hrs. after estrus begins
anterior lobe activity (Moore and Price, ’32).  


We may consider two further possibilities relative to continuous testicular
function :


(4) If the “brake actions” mentioned above are not present or present
Sow
only in a slight degree, a degree not sufficient to interrupt the activities
of the anterior lobe or of the sex gland, a more or less continuous
function of the testis may be maintained.


(5) When several or many environmental factors are concerned in producing testicular activity, a slight altering of one factor, such as light,
Silver fox
may prove insufficient to interrupt the pituitary-germ-gland relationship, and a continuous breeding state is effected in spite of seasonal
changes.


Underlying the above possibilities which may control testicular function is
Rat
the inherent tendency or hereditary constitution of the animal. In the final
analysis, it is this constitution which responds to environmental stimuli, and
moreover, controls the entire metabolism of the body. In other words, the
above-mentioned possibilities tend to oversimplify the problem. The organism as a whole must be considered; reproduction is not merely an environmentalpituitary-sex gland relationship.


F. Characteristics of the Male Reproductive Cycle and Its Relation to
15 days
Reproductive Conditions in the Female


As indicated above, reproduction in the male vertebrate is either a continuous process throughout the reproductive life of the individual or it is a
1-5 days; occurs once a year
discontinuous, periodic affair. In the continuous form of reproduction the
in February
activities of the seminiferous tubules and the interstitial or hormone-producing
tissues of the testis function side by side in a continuous fashion. In the
discontinuous, periodic type of testicular function, the activities of the seminiferous tubules and of the interstitial tissue do not always coincide. The
activities of the seminiferous tubules, resulting in the production of sperm
for a particular reproductive cycle, tend to precede, in some species by many
months, the activities of the sex-hormone-producing tissue. Evidently, the
output of the FSH and LH substances from the pituitary gland are spread
out over different periods of the year to harmonize with this activity of the
testicular components.


It will be seen in the next chapter that a continuous breeding faculty is
One determination estimates
not present in the female comparable to that of the male. All females are
estrus to be 9-20 hrs.; most  
discontinuous breeders. In some species, the cycles follow each other with
receptive to male about first
little rest between each cycle unless the female becomes pregnant or “broody.”
Some have a series of cycles over one part of the year but experience sexual
quiescence over the remaining portion of the year. However, in most female
vertebrates there is but one reproductive cycle per year.


In harmony with the above conditions, the continuous variety of testicular
3 hrs. of heat. Another determination estimates estrus
function is always associated with the condition in the female where more
to be 12-18 hrs.  
than one reproductive cycle occurs per year. Continuous reproductive conditions in the male, therefore, are adapted to serve one female two or more
times per year or several different females at intervals through the year.
Furthermore, the complicated, highly glandular, greatly extended type of
male-reproductive-duct system is adapted to conditions of (1) continuous
breeding, or (2) service to more than one female during one breeding season
of the year, whereas the simple type of reproductive duct is adapted to the
type of service where all or most of the genital products are discharged during
one brief period. In other words, the entire male reproductive system and reproductive habits are adapted to the behavior of female reproductive activities.  


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About 1-3 days after onset of estrus
1st or 2nd day of estrus


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. 1935b. Modifications of mammalian sexual cycles. III. Reversal of
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About 30 hrs. after mating
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De Robertis, E., Burgos, M. H., and
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involution occurs, and an anestrous interlude is established. Anestrus in the
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common rabbit, Oryctolagus cuniculus, occurs from October to March, but
of toad spermatozoa. Proc. Soc. Exper.
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our knowledge of the anterior pituitary
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and Simpson, M. E. 1950. Chap.  
Not all of the cyclic changes referred to above in those species which normally experience spontaneous ovulation are related to definite egg discharge.
Some cycles occur, more or less abortively, without ovulation of the egg. This
may happen in the human or in other mammals, such as the dog and monkey.  
Cycles without ovulations are called non-ovulatory cycles. Menstruation may
follow non-ovulatory cycles in the human female.  


VI. Physiology of the gonadotrophins in  
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The Hormones, II, by Pincus and Thimann. Academic Press, Inc., New York.


Felix, W. 1912. The development of the  
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urinogental organs in Manual of Human
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Embryology, by Keibal and Mall. J. B.
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Fevold, H. L. 1939. Chap. XVII in Allen,
(1) external environmental factors, such as light and temperature,  
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and Hisaw, F. L. 1934. Interactions of gonad-stimulating hormones in
(2) external factors governing food supply, and  
ovarian development. Am. J. Physiol.
109:655.


, , and Leonard, S. L. 1931.  
(3) internal factors resulting from an interplay of the activities of the pituitary gland, the ovary, general body health, and of the particular
hereditary constitution of the animal.  


The gonad-stimulating and the luteinizing hormones of the anterior lobe of  
These factors should be considered not alone in terms of the immediate
the hypophysis. Am. J. Physiol. 97:291.  
production of fertile conditions in the parent, but rather, in view of the total
end to be achieved, namely, the production of a new individual of the species.
For example, the reproductive cycle in the deer reaches its climax or estrus
in the autumn after a long period of lush feeding for the mother. The young
are born the next spring amid favorable temperatures, followed by another
period of bountiful food supply for the mother during lactation and for the  
fawn as it is weaned. A receding light factor in the late summer and early
fall thus may be correlated with the period of heat, which in turn proves to
be an optimum time of the year for conception with the resulting birth the  
following spring. Similarly, light ascendency is a factor in producing fertility in many birds. Here the incubation period for the young is short and a
plentiful supply of food awaits the parents and young when it is needed. In
other words, the factors which induce the onset of the reproductive state
are correlated with the conditions which enhance the end to be achieved,
namely, the production of a new individual.  


Glass, F. M. and Rugh, R. 1944. Seasonal
Let us consider next the internal factors which induce the breeding state
study of the normal and pituitary stimulated frog (Rana pipiens). 1. Testis and  
in the female mammal. The commonly held theory regarding the pituitaryovarian relationship governing the control of the reproductive periods in the
thumb pad. J. Morphol. 74:409.
mammal which ovulates spontaneously is as follows (figs. 53 and 59) :  


Creep, R. O., Fevold, H. L., and Hisaw,  
( 1 ) FSH of the pituitary gland stimulates later follicular growth. This factor
F. L. 1936. Effects of two hypophyseal
probably is aided by small amounts of the luteinizing factor, LH, to
gonadotrophic hormones on the reproductive system of the male rat. Anat.
effect an increased production by the ovarian tissues of the estrogenic
Rec. 65:261.
hormone. Early follicle growth probably occurs without FSH.  
 
Guthrie, M. J. 1933. The reproductive
cycles of some cave bats. J. Mammalogy.
14:199.  


Hammond, J. and Asdell, S. A. 1926. The
(2) Estrogen output by the ovary rises steadily during the period previous
vitality of the spermatozoa in the male
to ovulation.  
and female reproductive tracts. Brit. J.
Exper. Biol. 4:155.  


Henle, G. and Zittle, C. A. 1942. Studies
(3) Old corpora lutea or other ovarian tissue possibly secrete minimal
of the metabolism of bovine epididymal
amounts of progesterone under the influence of lutcotrophin, LTH.  
spermatozoa. Am. J. Physiol. 136:70.  


Hill, E. C. 1907. On the gross development and vascularization of the testis.
(4) As the quantity of estrogen rises in the blood stream, it inhibits the  
(Excellent figures showing migration of  
production of FSH and together with small quantities of progesterone,
the testes in the pig.) Am. J. Anat.  
increases the output of LH from the pituitary gland. This combination
6:439.  
also may cause an increased outflow of the luteotrophic factor.  


Hill, M. and Parkes, A. S. 1933. Studies
(5) An increased amount of LH aids in effecting ovulation and the subsequent luteinization of the follicle. As the follicle becomes converted
on the hypophysectomized ferret. Proc.
into the corpus luteum, the presence of the luteotrophic factor brings
Roy. Soc., London, s. B. 116:221.  
about the formation of increased quantities of progesterone and maintains for a time the corpus luteum and the functional luteal phase of
the cycle.  


(6) In those mammals possessing a scries of repeating sexual cycles, it
is assumed that the fall of estrogen in the blood stream after ovulation
suppresses the LH outflow and permits a fresh liberation of FSH
from the anterior lobe of the pituitary gland, thus starting a new cycle.
The lowering of the estrogen level may be particularly and immediately effective in forms such as the rat and mouse, which have a
short metestrus or luteal phase in the estrous cycle.


Hoover, E. E. and Hubbard, H. F. 1937.
e. Reproductive Cycle in Lower Vertebrate Females
Modification of the sexual cycle of trout
by control of light. Copeia. 4:206.  


Koch, F. C. 1942. Biol. Symp., The excretion and metabolism of the male sex
While the words estrus, heat, or rut are generally applied to the mammalian
hormone in health and disease. Jaques
groups, the recurrent periods of sexual excitement in lower vertebrates are
Cattell Press. 9:41.  
fundamentally the same sort of reaction, although the changes in the reproductive tract associated with ovarian events are not always the same as in
mammals. However, similar cyclic changes in the ovary and reproductive tract
are present in the lower vertebrates, and their correlation with the activities of the pituitary gland is an established fact. Consequently, the words estrus,
rut, sex excitement, and heat basically designate the same thing throughout
the vertebrate series — namely, a period during which the physiology and  
metabolism of the parental body is prepared to undertake the reproductive
functions. In this sense, the words estrus, anestrus, heat, etc. also may be
applied to the male as well as to the female when the male experiences periodic expressions of the sexual state.  


Leonard, S. L. and Kurzrok, R. 1946. Inhibitors of hyaluronidase in blood sera
Although the reproductive cycle in all vertebrates represents basically a
and their effect on follicle cell dispersal.
periodic development of the reproductive functions, there is a marked difference between the estrous cycle in the female mammal and the reproductive
Endocrinology. 39:85.  
cycle in most of the other female vertebrates with the exception of viviparous
forms among the snakes, lizards, and certain fishes. This difference is due
to the absence of a true luteal phase in the cycle. The follicular phase and
elaboration of estrogen appears to be much the same in birds, amphibia, and  
fishes as in the mammals, but the phase of the cycle governed by progesterone
secretion, associated with a gestational condition in the accessory reproductive
organs, is found only among those vertebrates which give birth to their  
young alive.  


Ludwig, D. J. 1950. The effect of androgens on spermatogenesis. Endocrinology.  
The reproductive cycles in certain vertebrates may be changed by selective
46:453.  
breeding and domestication. For example, the domestic hen is derived from
the wild jungle fowl. The jungle fowl conform to the general stimuli of nature
as do most wild birds, and the reproductive cycle is associated with a particular season of the year. However, domestication and selection by man of
certain laying strains have altered the original hereditary pattern of seasonal
laying. Consequently, good layers will lay eggs over an extended period of
the year, although there is a strong tendency to follow the ancestral plan by
laying most of the eggs during the spring and summer months; during the
fall and winter months, a smaller number of eggs are laid. Some of the varieties of the domestic hen conform more closely to the ancestral condition
than do other strains. Similar changes may be produced in the buffalo, which
in nature breeds in middle to late summer but in captivity has estrous periods
three weeks apart throughout the year (Asdell, ’46).  


Mann, T. 1949. Metabolism of semen.
G. Role of the Ovary in Gestation (Pregnancy)
Adv. in Enzymology. 9:329.


Marshall, F. H. A. 1911. The male generative cycle in the hedgehogs, etc. J.
1. Control of Implantation and the Maintenance of
Physiol. 43:247.
Pregnancy in Mammals


Mason, K. E. 1939. Chap. XXII in Allen,  
The ruling power of the ovary over the processes involved in pregnancy
et al.. Sex and Internal Secretions. 2d
is absolute, particularly during its earlier phases. In the first place, the corpusluteum hormone, progesterone, is necessary to change the uterus already conditioned by the estrogenic hormone into a functionally active state. The latter
ed.. The Williams & Wilkins Co., Baltimore.
condition is necessary for the nutrition and care of the embryo. A second
 
change which the gestational hormone imposes upon the genital tract of the
Matthews, S. A. 1938. The seasonal cycle
female is to quiet the active, irritable condition aroused by the estrogenic
in the gonads of Fiinditlus. Biol. Bull.  
factor. Progesterone thus serves to neutralize or antagonize the effects of
75:66.
the estrogenic hormone. A placid condition of the uterus must be maintained
 
during the period immediately following copulation if the fertilized egg is to
Mills, R. G. 1919. The pathological
be cared for within the uterine structure. Large doses of estrogens injected
changes in the testes in epidemic pneumonia. J. Exper. Med. 30:505.  
into mammals shortly after copulation prevent implantation of the embryo
 
in all species thus far studied. (See Selye, ’48, p. 822.)
Mitchell, G. A. G. 1939. The condition
of the peritoneal vaginal processes at
birth. J. Anat. 73:658.  


Moore, C. R. 1926. The biology of the  
A third effect of the presence of progesterone is the inhibition of the
mammalian testis and scrotum. Quart.  
copulatory responses. Immediately following estrus and ovulation, the female
Rev. Biol. 1:4.  
dog will fight off the aggressiveness of the male — an aggressiveness which
she invited a day or two previously. This change in behavior is introduced
by the development of the corpora lutea and the initiation of the luteal phase
of the reproductive cycle. Similar anaphrodisiac changes are sometimes mentioned in the behavior of the human female during the luteal phase of the
cycle. Progesterone injections also inhibit the copulatory responses in the  
ferret (Marshall and Hammond, ’44). All of the above-mentioned activities
of progesterone thus inhibit or antagonize the condition aroused by estrogenic
stimulation.  


. 1928. On the properties of the  
However, aside from these immediate metestrous and post-ovulatory changes
in behavior induced by progesterone, one of its most essential aetivities is
concerned with the maintenance of gestation or pregnancy. Ovariectomy or
the removal of the ovaries at any time during the gestational period in the
rat, mouse, and goat results in death and abortion of the embryo. During
the first part of pregnancy in the rabbit, the ovaries must be left intact but
may be removed in the closing phase without endangering the gestational
process. In the human female, and also in the mare, cat, dog, guinea pig,
and monkey, the ovaries may be removed during the latter half of pregnancy
without danger to the offspring. However, ovariectomy performed in the  
early stages of pregnancy in these animals, as well as in all other mammals
thus far studied, produces abortion (Pincus, ’36; Selye, ’48, p. 820). The
corpus luteum hormone, therefore, is essential in the early phases of gestation
in all mammals, and it appears to be necessary during most of the pregnant
period in many other mammals.


gonads as controllers of somatic and
It is highly probable that the placenta takes over the elaboration of progesterone in those mammals where ovariectomy is possible after the first part
psychical characteristics. J. Exper. Zool.  
of pregnancy has elapsed. In the human female the corpus luteum normally
50:455.  
involutes at about the third month of pregnancy, but progesterone may be
extracted from the placenta after this period.  


. 1939. Chap. VII, Part V, in Allen,
Although certain effects of the estrogenic hormone appear to be neutralized
(or antagonized) by progesterone during the early phases of reproduction,
other effects of estrogen in relation to progesterone are important for the
maintenance of the pregnant condition. In this connection the estrogenic
hormone appears to suppress some of the growth-promoting effects of progesterone. The two hormones thus work together to promote a gradual development of the uterine tissue and maintain a regulated, balanced condition
throughout pregnancy. The placenta, through its ability to elaborate progesterone and estrogen during the latter phases of pregnancy, is an important
feature regulating pregnancy in some mammals.


et al.. Sex and Internal Secretions. 2d
It should be emphasized in connection with the above statements that the
ed.. The Williams & Wilkins Co.. Baltimore.  
presence of the fertilized egg and its subsequent development in some manner
affects the maintenance of the corpus luteum. The mechanism by which this
influence is conveyed to the ovary is unknown.  


. 1942. Physiology of the Testis in
2. Gestation Periods, in Days, of Some Common Mammals*


Glandular Physiology and Therapy. 2d
* Adapted from Asdell, ’46; Cahalane, ’47; Kenneth, ’43.  
ed.. Am. M. A. Council on Pharmacy
and Chemistry. Chicago.  


and McGee, L. C. 1928. On the


effects of injecting lipoid extracts of bull
Armadillo (Dasypus novemcinctus)
testes into castrated guinea pigs. Am. J.
Physiol. 87:436.


and Price, D. 1932. Gonad hormone functions and the reciprocal influence between gonads and hypophysis with its bearing on the problem
150
of sex hormone antagonism. Am. J.
Anat. 50:13.


Pincus, G. and Thimann, K. V. 1950. The
Bear, black (Ursiis americanus)
Hormones, Vol. II. Academic Press, Inc.,
New York.


Rasmussen, A. T. 1917. Seasonal changes
210
in the interstitial cells of the testis in the
woodchuck (Marmota monax). Am. J.
Anat. 22:475.


Riley, G. M. 1937. Experimental studies
Bear, polar (Thalarctos maritimus)  
on spermatogenesis in the house sparrow, Passer dornesticus (Tinnaeus). Anat.
Rec. 67:327.


Robson, J. M. 1940. Recent Advances in
240
Sex and Reproductive Physiology. J. &
A. Churchill, Ltd., London.


Rowlands, J. W. 1944. Capacity of hyaluronidase to increase the fertilizing power
Beaver, Canadian (Castor canadensis)
of sperm. Nature, London. 154:332.


Sehulte, T. L. 1937. The genito urinary
94-100
system of the Elephas indie us male. Am.
J. Anat. 61:131.


Schwenk, E. 1944. Synthesis of the steroid
Bison (Bison bison)
hormones. Page 129 in The chemistry
and physiology of hormones. Publication
of Am. A. Adv. Sc.


Smith, P. E. 1939. Chap. XVI in Allen,
276
et al.. Sex and Internal Secretions. 2d
ed.. The Williams & Wilkins Co., Baltimore.


Turner, C. D. 1948. Chap. 12 in General
Cat, domestic (Felis catus)
Endocrinology. W. B. Saunders Co.,
Philadelphia.


Turner, C. L. 1919. The seasonal cycle in
60
the spermary of the perch. J, Morphol.
32:681.


van Oordt, G. J. 1923. Secondary sex
Cattle (Bos taurus)  
characters and testis of the ten spined
stickleback (Gasterosteus pungitius).
Proc. Kon. Akad. Wetensch., Amsterdam. 26:309.


Weber, M. 1928. Die Saiigetiere. Gustav
282
Fischer, Jena.


Wells, L. J. 1935. Seasonal sexual rhythm
Chimpanzee (Pan satyrus)  
and its modification in the experimental
male of the thirteen-lined ground squirrel
(Citellus tridecemlineatus). Anat. Rec.
62:409.


. 1943. Descent of the testis: anatomical and hormonal considerations.
250
Surgery. 14:436.
 
Deer, Virginian (Odocoileus virginianus)
 
160-200


Dog, domestic (Canis familiaris)


Williams, R. G. 1950. Studies of living
58-65
interstitial cells and pieces of seminiferous tubules in autogenous grafts of testis.
Am. J. Anat. 86:343.


Wislocki, G. B. 1933. Location of the
Donkey, domestic (Eqiius asinus)
testes and body temperature in mammals. Quart. Rev. Biol. 8:385.


. 1943a. Studies on the growth of
365-380


deer antlers: 1. On the structure and
Elephant (Elephas africanus)  
histogenesis of the antlers of the Virginia
deer (Odocoileus virginianus borealis).
Am. J. Anat. 71:371.


. 1943b. Studies on growth of deer
641


antlers: 11. Seasonal changes in the male
Elephant (Elephas indicus)  
reproductive tract of the Virginia deer
(Odocoileus virginianus borealis); with
a discussion of the factors controlling
antler-gonad periodicity. Essays in Biology In Honor of Herbert H. Evans. The
University of California Press, Berkeley
and Los Angeles.


. et al, 1947. The effects of gona
607-641
dectomy and the administration of testosterone propionate on the growth of
antlers in male and female deer. Endocrinology. 40:202.


Yeates, N. T. M. 1947. Influence of variation in length of day upon the breeding season in sheep. Nature, London.
Elk (A Ices alces)
160:429.


Young, W. C. 1929. The influence of high
250
temperature on the reproductive capacity
of guinea pig spermatozoa as determined
by artificial insemination. Physiol. Zodl.
2 : 1 .


1931. A study of the functions of the epididymis. 111. Functional changes
Ferret (Putorius faro)
undergone by spermatozoa during their
passage through the epididymis and vas
deferens of the guinea pig. Brit. J. Exper.
Biol. 8:151.


Zondek, B. 1930. Uber die Hormone des
42
Hypophysenvorderlappens. 1. Wachstumshormon, Follikelreifungshormon
(Prolan A). Luteinisierungshormon
(Prolan B) Stoffwechselhormon? Klin.
Wchnschr. 8:245.


==The Vertetrate Ovary and Its Relationship to Reproduction==
Fox, arctic (Alopex lagopus)
===A. The Ovary and Its Importance===


One of the editions of the treatise on development, “Exercitationes de
60
Generatione Animalium,” by William Harvey (1578-1657) contains a picture of Jupiter on a throne opening an egg from which various animals,
including man, are emerging (fig. 25). Upon the egg (ovum) are engraved
the words ovo omnia.'' At the heading of chapter 62 of this work Harvey
placed a caption which explains the phrase ex ovo omnia more explicitly.
This heading reads: “Ovum esse primordium commune omnibus animalibus”
— the egg is the primordium common to all animals. Published in 1651, this
statement still maintains its descriptive force.


Many individual animals arise by asexual reproduction, that is, through
Fox, red (Vulpes vulpes and V. fulva)  
a process of division or separation from a parent organism. In the phylum
Chordata asexual reproduction is found among the Urochordata, where new individuals may arise by budding from a stolon -like base of the parent (fig.  
27). This process often is called gemmation, the formation of a new individual by a protrusion of a mass of cells from the parental body followed by
its partial or complete separation. It is a prominent method of reproduction
among the lower Metazoa, particularly the coelenterates and sponges. Nevertheless, all animal species among the Metazoa ultimately utilize an egg as
the primordium from which the new individual arises. Sexual reproduction,
generally associated with the fertilization of an egg by a sperm element, appears
to be a needful biological process.


52-63


Giraffe (Giraffa Camelopardalis)


450


Fig. 25. Copy of the engraved title appearing in one edition of Harvey’s dissertation
Goat, domestic (Capra hircus)
on generation as shown on p. 139 of Early Theories of Sexual Generation by E. J. Cole.
Observe the words “ex ovo omnia” upon the egg which Jupiter is opening. Various animals
are emerging from the egg.


Fig. 26. Copy of Hartsoeker’s figure of human spermatozoan, containing the homonculus or “little man,” published in 1694. This figure represents a marked preformationist
140-160
conception of development. However, it is to be noted that Hartsoeker later abandoned
the preformationist concept as a result of his studies on regeneration.


Guinea pig (Cavia porcellus)


68-71


Horse (Equus cabaltus)


True as the general statement made by Harvey may be, it is not clear what
330-380
is meant by the word ovum or egg. We know certain of its characteristics,
but, for the most part, it must be accepted as an accomplished fact enshrouded
in mystery. To Harvey the egg was an indefinite, unorganized association of
substance plus a “primordial generative principle” (see Cole, F. J., ’30, p.
140), Other minds have conceived of other meanings. Nevertheless, descriptive
and experimental embryology has forced the conclusion that the egg, during
its development within the ovary, experiences a profound process of differentiation, resulting in the formation of an invisible organization. Although this organization is invisible, it is imbued with an invincibility which, when
set in motion at the time of fertilization, drives the developmental processes
onward until final fulfillment is achieved in the fully formed body of the
adult organism.


Man (Homo sapiens)
270-295
Lion (Felis leo)


106


Fig, 27. Forms of asexual reproduction in the subphylum Urochordata 9 #
Lynx (Lynx canadensis)


Chordata. (From MacBride: Textbook of Embryology, Vol. 1, Londo/rt', ^
63


(A) Budding from "stolon of Perophora listeri, from MacBride after (jR) , (C)  
Marten, American (Martes americana)  


Two stages of budding in an ascidian, from MacBride after Pizon
267-280


Mink (Mustela vison)


42-76


Beyond the fundamental changes effected in the developing egg while in
Mole (Talpa europaea)
the ovary, the latter structure has still other roles to maintain. Through the
mediation of the hormones produced within the confines of the ovarian substance, the female parent is prepared to assume the responsibilities of reproduction. In addition, in many vertebrates the further responsibility of taking
care of the young during the embryonic period stems from the hormones
produced in the ovary. In some vertebrates, the instinct of parental care of
the young after hatching or after birth indirectly is linked to ovarian-pituitary
relationships. Because of these profound and far-reaching influences which
the ovary possesses in producing the new individual, it must be regarded as
the dynamic center of reproduction for most animal species.


===B. Preformationism, Past and Present===
30


The above statement relative to the importance of ovarian influences and
Monkey, macaque (Macaca mulato)  
of the female parent is a position far removed from that held by some in the
 
past. An ancient belief elevated the male parent and his “seed” or semen.
160-179
As Cole, F. J., ’30, p. 38, so aptly places the thinking of certain learned
sources during the 16th century: “The uterus is regarded as the ‘till’d ground
for to sow the seeds on’ — a popular idea, based obviously on the analogy
with plants, which prevailed long before and after this period. The seed of
the male is therefore the chief agent in generation, but cannot produce an
embryo without the cooperation of the female, and whether the result is male
or female depends on which side of the uterus the seed falls, the time of the
year, temperature, and the incidence of menstruation.” Or, in reference to
the Leeuwenhoek’s belief in an intangible preformationism, Cole, F. J., ’30,
p. 57, states: “He asserts that every spermatic animalcule of the ram contains
a lamb, but it does not assume the external appearance of a lamb until it has
been nourished and grown in the uterus of the female.” This statement of
A. van Leeuwenhoek (1632-1723) was made as a criticism of N. Hartsoeker
(1656-1725) whose extreme adherence to a seminal preformationism led
him to picture the preformed body of the human individual, the homonculus,
encased within the head of the spermatozoon (fig. 26). Hartsoeker, however,
later abandoned this idea.


In fairness it should be observed that the egg during these years did not
Mouse, house (Mas rnusculus)  
lack champions who extolled its importance. While the Animalculists considered the sperm cell as the vital element in reproduction, the Ovists, such as
Swammerdam (1637-80), Haller (1708-77), Bonnet (1720-93) and Spallanzani (1729-99) believed that the pre-existing parts of the new individual
were contained or preformed within the egg.


20-21


An extreme form of preformationism was advocated by certain thinkers
Opossum (Didelphis virginiana)
during this period. For example, Bonnet championed the idea of encasement
or “emboitement.” To quote from Bonnet:


The term “emboitement” suggests an idea which is not altogether correct. The
13
germs are not enclosed like boxes or cases one within the other, but a germ forms
 
part of another germ as a seed is a part of the plant on which it develops. This
Pig (Sus scrofa)
seed encloses a small plant which also has its seeds, in each of which is found a
 
plantule of corresponding smallness. This plantule itself has its seeds and the latter
115-120
bears plantules incomparably smaller, and so on, and the whole of this ever
diminishing series of organized beings formed a part of the first plant, and thus
arose its first growths. (Cole, ’30, p. 99.)


On the other hand, there were those who maintained that for some animals,
Rabbit (Lepus; Sylvilagus; Oryctolagus)  
neither the sperm nor the egg were important as “many animals are bred
without seed and arise from filth and corruption, such as mice, rats, snails,
shell fish, caterpillars, moths, weevils, frogs, and eels” (Cole, ’30, p. 38).
This concept was a part of the theory of spontaneous generation of living
organisms -a theory ably disproved by the experimental contributions of
three men: Redi (1626-97); Spallanzani; and Louis Pasteur (1822-95).


Modern embryology embraces a kind of preformationism, a preformationism which does not see the formed parts of the new individual within
30-43
the egg or sperm but wi.ich does see within the egg a vital, profound, and
highly complex physiochemical organization capable of producing a new individual by a gradual process of development. This organization, this selfdetermining mechanism, is resident in the nucleus with its genes and the
organized cytoplasm of the fully developed oocyte or egg. However, as shown
later, this organization is dependent upon a series of activating agencies or
substances for its ultimate realization. Some of these activating substances
come from without, but many of them are produced within the developing
organism itself.


===C. General Structure of the Reproductive System of the Vertebrate Female===
Rats (Various species)


====1. General Structure of the Ovary====
21-25


Morphologically, the ovary presents a series of contrasts in the different
Seal, fur (Callorhinus sp.)  
vertebrate classes. In teleost fishes the size of the ovary is enormous compared
to the body of the female (fig. 28), while in the human (fig. 29), cow, sow,
etc., it is a small structure in comparison to the adult body. Again, it may
contain millions of mature eggs in the ling, cod and conger, during each breeding season, whereas only a single egg commonly is matured at a time in the
cow, elephant, or human. During the reproductive season the ovary may
assume a condition of striking colored effects as in the bird, reptile, shark,
and frog, only to recede into an appearance drab, shrunken, and disheveled
in the non-breeding season.


340-350


Sheep, domestic (Ovis aries)


Fig. 28. Dissection of female specimen of the common flounder, Limanda ferruginea.
144-160
It particularly shows the ovary with its laterally placed ovarian sinus. Observe that the
ovary, during the breeding season, is an elongated structure which extends backward into
the tail. There are two ovaries, one on either side of the hemal processes of the caudal
vertebrae.


Its shape, also, is most variable in different species. In mammals it is a
Skunk, common (Mephitis mephitis)
flattened ovoid structure in the resting condition, but during the reproductive
phase it may assume a rounded appearance, containing mound-like protrusions.
In birds and reptiles it has the general form of a bunch of grapes. In the
amphibia it may be composed of a series of lobes, each of which is a mass
of eggs during the breeding season, and in teleost and ganoid fishes it is
an elongated structure extending over a considerable area of the body.


Regardless of their many shapes and sizes, the ovaries of vertebrates may
63
be divided morphologically into two main types, namely, compact and saccular
forms. The compact type of ovary is found in teleost, elasmobranch, cyclostome, ganoid, and dipnoan fishes, as well as in reptiles, birds and mammals.
It has the following regions (figs. 30, 31):


( 1 ) the medulla, an inner zone containing relatively large blood and lymph
Squirrel, red (Tamiasciurus sp.) 30-40
vessels;


(2) the cortex, an area outside of and surrounding the medulla (except
Tiger (Felis tigris) 106
at the hilus), containing many ova in various stages of development;


(3) a tunica albuginea or connective-tissue layer surrounding the cortex;
Whale (Various species) 334-365
and


(4) the germinal epithelium or the covering epithelium of the ovary.
Wolf (Canis lupus) 63


The germinal epithelium is continuous with the mesovarium, the peritoneal
Woodchuck (Marmota monax) 35-42
support of the ovary, and the particular area where the mesovarium attaches
to the ovary is known as the hilus. Within the mesovarium and passing
through the hilus are to be found the blood and lymph vessels which supply
the ovary (fig. 30).


The ovary of the teleost fish is a specialized, compact type of ovary adapted
Zebra, mountain (Equus zebra) 300-345
to the ovulation of many thousands, and in pelagic species, millions of eggs
at one time. It has an elongate hilar aspect which permits blood vessels to
enter the ovarian tissue along one surface of the ovary, whereas the opposite
side is the ovulating area. In many teleosts the ovulating surface possesses
a special sinus-like space or lumen (fig. 28) which continues posteriad to
join the very short oviduct. At the time of ovulation the eggs are discharged
into this space and move caudally as the ovarian tissue contracts. In other
teleosts this ovulatory space is not a permanent structure but is formed only
at the time of ovulation. In Tilapia macrocephala, for example, the ovulatory
lumen is formed on the side of the ovary opposite the area where the blood
vessels enter. The formation of this space at the time of ovulation is described
by Aronson and Holz-Tucker (’49) as a rupture of the elastic follicles during
ovulation whereupon the follicle walls shrink toward the ovarian midline.




3. Maintenance of Pregnancy in Reptiles and Other
Vertebrates


Fig. 29. Diagrammatic representation of a midsagittal section of the reproductive
In certain viviparous species of the genera Storeria, Matrix and Thamnophis,
organs of the human female. (Slightly modified from Morris: Human Anatomy, Philadelphia, Blakiston.)
Clausen (’40) reports that ovariectomy during gestation results in resorption
 
of the embryo when performed during the earlier phases of gestation and
abortion during the middle of gestation, but during the terminal portion of  
pregnancy the process is unaffected and the young are born normally. These
results are similar to those obtained from the rabbit as noted previously.  


While experimental evidence is lacking in other vertebrate groups which
give birth to the young alive, the evidence obtained from reptilian and mammalian studies suggests that hormones are responsible for the maintenance
of pregnancy. In harmony with this statement, it may be pointed out that
in the viviparous elasmobranch fishes (e.g., sharks) corpora lutea are developed in the ovaries.


Fig. 30. Schematic three-dimensional representation of the cyclic changes which occur in the mammalian ovary.
H. Role of the Ovary in Parturition or Birth of the Young


The real factors bringing about parturition are not known, and any explanation of the matter largely is theoretical. However, certain aspects of
the subject have been explored. For example, it was observed above that
progesterone appears to antagonize the action of estrogen with the result
that the uterus stimulated to irritability and contractility under the influence
of estrogen is made placid by the action of progesterone. In harmony with
this action studies have shown that estrogen tends to increase during the
final stages of normal gestation, while progesterone appears to decrease, accompanied by an involution of the corpora lutea. Consequently, the foregoing
facts have suggested the “estrogen theory,” which postulates that activities
of the uterine musculature are increased by the added amounts of estrogen
in the presence of decreasing amounts of progesterone during the latter phases
of pregnancy. In confirmation of this theory, it has been shown that progesterone injected into a pregnant rabbit near the end of the gestation period
will tend to prolong gestation. A second theory of parturitional behavior
assumes that the posterior lobe of the pituitary gland elaborates oxytocin
which induces increased uterine activity, resulting in birth contractions
(Waring and Landgrebe in Pincus and Thimann, ’50). Again, a third concept
emphasizes Ihe possibility that the placenta may produce substances which
bring about contractions necessary for the expulsion of the young (Turner,
’48, p. 428). Oxytocic substances have been extracted from the placenta,
which suggests the validity of this theory.


carrying the interstitial tissue and immature ova. This shrinking away of the
tissues of the ovary leaves a space between these tissues and the outside
ovarian wall. A lumen thus is formed along the lateral aspect of the ovary
which is continuous with the oviduct. Many teleosts have two ovaries (e.g.,
flounder); in others there is but one (e.g., perch).


The amphibia possess a true saccular ovary (fig. 32). It has a cortex and  
Fig. 54. Changes occurring in the reproductive organs and mammary glands of the  
germinal epithelium somewhat similar to the compact ovarian variety, but
bitch during the reproductive cycle. The student is referred to Asdell (’46), pp. 150-156
the area which forms the medulla in the compact ovary is here represented
and Dukes (’43), pp. 678-682, for detailed description and references pertaining to the  
by a large lymph space. During early development, the amphibian ovary is
data supporting this chart. The gestation period is based upon data supplied by Kenneth
a compact structure, but later there is a hollowing out and disappearance of
(’43) and the author’s personal experience with dogs.  
the compact medullary portion, and the cortical area remains as a relatively
thin, peripheral region (Burns, ’31; Humphrey, ’29).  
 
Histologically the vertebrate ovary is composed of two general cellular
groups, namely:


(1) germ cells, and


(2) general tissue cells of various kinds, such as epithelium, connective
Fig. 55. Reproductive and pregnancy cycles in the sow. (Modified from data supplied
tissue, smooth muscle fibers, and the complex of elements comprising the vascular system of the ovary (figs. 30, 32). Some of the general
by Corner, Carnegie Inst., Washington, pub. 276, Contrib. to Embryol., 13; the parturition
cells form the so-called interstitial tissue of the ovary.  
data derived from Kenneth, ’43.)


The germ cells differ from the general cells in that each of them has a
latent potency for developing a new individual. This latent condition is converted into active potentiality during the differentiation of the primitive germ
cell into the mature egg or ovum.


===2. General Structure of the Accessory Reproductive Organs===
The specific functions of the ovary in parturition probably are more pronounced in those forms where it is essential throughout most of the gestational period, such as the viviparous snakes, and among the mammals, such
forms as the opossum, rat, mouse, and rabbit. The waning of corpus-luteum
activity in these species may serve to lower the level of progesterone in the
body and thus permit some of the other factors, such as estrogen or the
pituitary principle, to activate the uterus.


The accessory reproductive structures of the female vertebrate may be
Another factor associated with the ovary and parturition is the hormone
separated into three general types, viz.:
relaxin. This substance was first reported by Hisaw and further studied by
this investigator and his associates (Hisaw, ’25, ’29; and Hisaw, et al., ’44).  


( 1 ) the total absence of or the presence of a pair of short funnel-like
structures which convey the eggs from the peritoneal cavity through




Fig. 56. Reproductive and pregnancy cycles in the mare. (Parturition period based
upon data supplied by Kenneth (’43); other data supplied by Asdell (’46) and Dukes
(’43).) It is to be noted that the first corpus luteum of pregnancy degenerates after
about 35 days; the second “crop of corpora lutea” (Asdell) degenerate by 150 days. The
ovaries may be removed after 200 days of pregnancy without causing abortion of young.


Fig. 31 . Three-dimensional representation of the bird ovary together with the funnel
Relaxin aids in the production of a relaxed condition of the pelvic girdle, a
portion (infundibulum) of the oviduct. Recently ovulated egg is shown in the process of  
necessity for the formation of a normal birth passageway for the young.  
engulfment by the infundibulum. Various stages of developing eggs are shown.  
Relaxin somehow is associated in its formation with the presence of progesterone in the blood stream and also with the intact reproductive system.
Relaxin together with estrogen and progesterone establishes a relaxed condition of the tissues in the pubic area of the pelvic girdle.  


I. Importance of the Ovary in Mammary-Gland Development
and Lactation


Fig. 32. Anterior half of the saccular ovary of Necturus maculosus.
Estrogen and progesterone together with the lactogenic hormone, luteotrophin, of the pituitary gland are necessary in mammary-gland development.  
The entire story of the relationship of these and of other factors in all mammals or in any particular mammal is not known. However, according to one
theory of mammary-gland development and function, the suggestive roles
played by these hormones presumably are as follows (fig. 58): Estradiol and
other estrogens bring about the development of the mammary-gland ducts;
as a result a tree-like branching of the ducts is effected from a simple im


an opening into the urogenital sinus and thence to the outside as in
cyclostome fishes,


(2) a short sinus-like tube attached to each ovary and to the urogenital
Fig. 57. Reproductive and pregnancy cycles in the cow. (Parturition period based upon
sinus or to a separate body opening as in many teleost fishes (fig.
data supplied by Kenneth (’43), also by Asdell (’46), Other data for chart derived from
28), and
Asdell (’46).


(3) two elongated oviducal tubes variously modified (figs. 29, 33, 34,  
Three main characteristics of heat or estrous period are evident: (1) A duration of
35, 36, 37).  
heat of only about 10 to 18 hours; (2) abundant secretion during heat of a “stringy
mucus,’’ derived from mucoid epithelium of vagina and from sealing plug of cervix when
cow not in estrus (Asdell); and (3) ovulation occurs from 13Vi to 15Vi hours after termination of estrus (Asdell), Variation in time of ovulation may be considerable, from
2 hours before end of estrus to 26 hours after (Asdell).
 
mature pattern established during earlier development (fig. 5 8 A, A', B). The
male mammary gland may remain similar to the condition shown in fig. 58A.
The maturing of the egg follicles within the ovary and the concomitant formation of estrogen which accompanies sexual maturity is linked with the
more complex state of the mammary-gland system shown in fig. 58B.
 
The next step of mammary-gland development is carried out under the
influence of progesterone. Progesterone is necessary for the development
of the terminal glandular tissue or alveoli associated with these ducts (fig.
58C, D). Finally, the pituitary lactogenic hormone (luteotrophin [LTH];
prolactin) stimulates the actual secretion of milk (fig. 58E). Recent research
also has shown that the lactogenic hormone collaborates in some way with
estrogen and progesterone in the development of the mammary-gland tissue.  


Except in the teleost fishes the cephalic end of each oviduct generally is
open and is placed near the ovary but not united directly with it (figs. 29,
33) although in some species, such as the rat, it is united with an ovarian
capsule (fig. 37). In some vertebrates the anterior orifice of the oviduct may
be located a considerable distance from the ovary, as in frogs, toads, and
salamanders. In many vertebrates, as in birds and snakes, there is but one
oviduct in the adult.


In some vertebrates the oviduct is an elongated glandular tube, as in certain
urodele amphibia (fig. 33) and in ganoid fishes; in others, such as frogs,
birds or mammals, it is composed of two main parts: ( 1 ) an anterior glandular
structure and (2) a more caudally placed uterine portion. The latter may
unite directly with the cloaca, as in the frog (fig. 38) or by means of a third
portion, the vaginal canal or vagina located between the uterus and the
cloaca, as in elasmobranch fishes, reptiles, and birds, or between the uterus
and the external urogenital sinus, as in mammals (figs. 35, 36, 37). The
vaginal canal may be single, as in eutherian mammals, or double, as in metatherian mammals (figs. 35, 36). In metatherian (marsupial) mammals it
appears that a third connection with the oviducts is made by the addition
of a birth passageway. This birth canal represents a secondary modification
of a portion of the vaginal canals and associated structures (figs. 34, 35, 114).
(See Nelsen and Maxwell, ’42.) One of the main functions of the vagina or
vaginal canal is to receive the intromittent organ of the male during copulation.




The anterior opening of the oviduct is the ostium tubae abdominale, a  
Fig. 58. Mammary gland changes in relation to reproduction. (Figures are a modification of a figure by Corner: Hormones in Human Reproduction, Princeton, Princeton
funnel-shaped aperture generally referred to as the infundibulum. In the  
University Press. The figure in the latter work was based on a figure by C. D. Turner:
transport of the egg from the ovary to the oviduct the infundibulum, in  
Chap. XI of Sex and Internal Secretions, by Allen, et al., Baltimore, Williams & Wilkins,
many species, actually engulfs and swallows the egg.  
1939.) Factors involved in mammary gland development and secretion are somewhat as
follows: (A, A') Condition of the young, infantile gland. (B) Development from a
simple, branched, tubular gland of the immature animal (A') into a compound tubular
gland presumably under the direct stimulation of estrogen, according to one theory, or
by the action of estrogen upon the pituitary gland which then releases mammogen I,
producing these changes, according to Turner, et al.: Chap. XI, Sex and Internal Secretions, by Allen, et al., Baltimore, Williams & Wilkins. (C) Transformation of the compound tubular gland into a compound tubulo-alveolar gland under the influence of progesterone, during the first part of pregnancy, or, according to Turner, et al., by the influence
of estrogen plus progesterone which causes the pituitary to release a second mammogen
which produces the alveolar transformation. (D) Effect of the latter part of pregnancy
is to bring about a development of the cells of the acini of the acinous or alveolar system.
The unit shown in (D) represents a simple, branched, acinous gland, in which there are
six alveoli or acini associated with the duct. (E) Affect of parturition is to release the
lactogenic hormone (prolactin; luteotrophin) from the pituitary gland which brings about
milk secretion. During pregnancy the high levels of estrogen presumably inhibit milk
secretion. However, following pregnancy the level of estrogen is lowered permitting
lactogenic-hormone action upon the alveoli of the gland.  


The portion of the oviduct anterior to the uterus often is called the convoluted glandular part; it is highly twisted and convoluted in many species.  
The removal of the placenta and embryo at any time during gestation permits milk
In amphibians, reptiles, birds, and in some mammals the glandular portion
flow, provided the mammary glands are sufficiently developed. In the human, any remains
of the placenta after birth inhibit milk secretion, probably because the estrogenic hormone
is elaborated by the placental remnants. (See Selye, ’48, p. 829.)


In the rabbit, estrogen and progesterone are necessary for the elaboration of the duct
and secretory acini; in the guinea pig and goat, and to some extent in the primates,
including the human female, estrogen alone is capable of producing the development of
the entire duct and acinous system. (See Turner, ’48, p. 430.)




Fig. 33. Diagrammatic representation of the reproductive structures of female urodele,
During pregnancy, the actual secretion of milk is inhibited by the estrogenic
hormone produced by the ovary and the placenta. The role of estrogen as
an inhibitor of lactation is suggested by the fact that, after lactation has started
following normal parturition, it is possible in the cow and human to suppress
milk flow by the administration of estrogens. After parturition, however,
estrogen is no longer present in^sufflcient amounts to suppress the secretion
of milk, and the mammary gland begins to function. (In the fur seal a postpartum estrus with ovulation follows a short time after parturition. However,
the amount of estrogen produced by this reproductive cycle is not sufficient
to curb lactation.) The neurohumoral reflex, or “suckling reflex,” produced
by the sucking young appears to maintain the flow of milk over a period of
time. Probably this reflex causes a continuous discharge of the lactogenic hormone from the anterior lobe of the hypophysis.


Necturus maculosus.
Another theory of mammary-gland development maintains that estrogen
 
stimulates the anterior pituitary gland to release mammogen, which causes
 
development of the duct system, and estrogen plus progesterone induce a
Fig. 34. Diagrammatic lateral view of female reproductive system of the opossum,  
second mammogen which stimulates lobule-alveolar development. The lactogenic hormone produces the actual secretion of milk. The ovary thus assumes considerable importance in controlling the (morphological) development of the mammary glands in mammals, particularly in those forms in
showing pseudo-vaginal birth canal.  
which the functional condition of the ovary is maintained throughout most of the gestational period, e.g., rat, rabbit, dog, etc. In other species, such as
the human, mare, etc., the placenta through its ability to duplicate the production of the ovarian hormones, assumes a role during the latter phase of
pregnancy. (For further details, consult Folley and Malpress in Pincus and
Thimann, ’48; Selye, ’48, pp. 828-832; and Turner, ’48, pp. 428-448.)






Fig. 35. Reproductive structures of female opossum shown from the ventral view. Observe that the ovary and infundibular portion of the Fallopian tube lie dorsal to the horn
Fig. 59. Stages in the reproductive cycle of the human female and its pituitary-ovarianendometrial relationships (Cf. fig. 53). (Compiled from various sources in the literature.)
of the uterus.  
(a) As shown at the extreme right of the figure, a fall in the level of estrogen and progesterone in the blood stream, either or both, is associated with endometrial necrosis, bleeding, and discharge (menstruation), (b) The lowering of the estrogen level is associated
with a new outflow of the follicle-stimulating hormone (FSH), as shown at the right of
the figure, (c) In the left side of the figure, the influence of FSH induces egg follicles,
probably several, to grow. Antral spaces appear and enlarge. The presence of a small
amount of the luteinizing hormone (LH) together with FSH stimulates the secretion of
estrogen by the ovarian tissues, possibly by the follicles and interstitial tissue between
the follicles, (d) In consequence, the estrogen level rises in the blood stream, and
menstruation subsides by the fourth day. (e) The continued influence of estrogen produces endometrial growth, and probably increases the outflow of LH from the pituitary
(fig. 53). It is probable, also, that the increased estrogen level stimulates a release of
the luteotrophic hormone from the pituitary, which in turn stimulates the formation of
a small quantity of progesterone by either the interstitial tissue of the ovary or in old
corpora lutea. (f) Some of the developing egg follicles degenerate, while one continues
to develop, (g) The elevation of estrogen suppresses the outflow of FSH as indicated
by the heavy broken line to the left, (h) The elevated level of estrogen together possibly
with small amounts of progesterone evokes an increased outflow of LH and LTH as
indicated by the heavy broken line to the right, (i) LH and FSH bring about ovulation
at about the fourteenth day. (j) LH causes development of corpus luteum. (k) LTH
elicits secretion of progesterone by corpus luteum. Possibly some estrogen is secreted
also by corpus luteum. (1) Progesterone and estrogen stimulate added development of
endometrium, (m) In the absence of fertilization of the egg, the corpus luteum regresses,
with a subsequent fall of progesterone and estrogen levels in the blood stream, terminating
the cycle and permitting a new menstrual procedure.  


functions to secrete an albuminous coating which is applied to the egg during
its passage through this region. In amphibians, reptiles, and birds it forms
the major portion of the oviduct, but in mammals it is much reduced in size
and extent. In the latter group it is referred to as the uterine or Fallopian tube.


The uterus is a muscular, posterior segment of the oviduct. Like the  
In the dog or opossum during each reproductive cycle, the mammary glands
anterior glandular portion of the oviduct, it also has glandular functions, but
are stimulated to grow and may even secrete milk (dog). These changes
these are subservient to its more particular property of expanding into an
closely parallel the ovarian activities, particularly the luteal phase of the cycle.  
enlarged compartment where the egg or developing embryo may be retained.  
In the human, functional growth changes occur in pregnancy, but, pending
The protection and care of the egg or of the embryo during a part or all of
the events of the ordinary cycle, alterations in the duct system are slight although the breasts may be turgid due to increased blood flow and connectivetissue development.  
its development, is the main function of the uterus in most vertebrates. In the  
frogs and toads, however, this structure seems to be concerned with a “ripening” process of the egg. Large numbers of eggs are stored in the uterine sac
of the frog for a period of time before spawning.  


Various degrees of union between the uterine segments of the two oviducts are found in mammals. In the primates they fuse to form a single
J. Other Possible Developmental Functions Produced by the Ovary
uterine compartment with two anterior uterine tubes (fig. 29). In carnivores,
there is a caudal body of the uterus with two horns extending forward to
unite with the uterine tubes (fig. 36). In the rat and mouse, the uterine segments may be entirely separate, coming together and joining the single vaginal
chamber (fig. 37). In the opossum the uterine segments are entirely separated,
joining a dual vaginal canal system posteriorly (figs. 34, 35, 114).


As the eggs of the opossum and rabbit travel through the uterine (Fallopian) tube toward the uterus, they are coated with an albuminous, jelly-like
coating. Similar jelly coatings are added to the eggs of the bird, reptile, frog,
toad, and salamander. These coatings or membranes added to the egg as it
travels through the oviduct are known as tertiary egg membranes.


===D. Dependency of the Female Reproductive System on General Body===
In the toad, the secretion of the protective jelly by the oviduct can be
elicited by the lactogenic hormone present in beef pituitary glands. The secretion of the albuminous jelly coatings around the eggs of frogs, salamanders,
reptiles, and birds may be related to this hormone. The formation of the
crop milk of pigeons has been shown by Riddle and Bates (’39) to be dependent upon the presence of the lactogenic hormone.


Conditions
The function of the ovary in influencing the outflow of the lactogenic hormone from the pituitary, if present in the above cases of glandular secretion,
must be an indirect one. Evans and Simpson in Pincus and Thimann (’50)
ascribe the outflow of the “lactogenic hormone (luteotrophic hormone)” of
the mammalian pituitary to estrin produced by the ovary. It is possible that
in the salamanders, frogs, toads, and the birds an indirect ovarian influence
may similarly induce secretion of the lactogenic hormone which in turn governs the elaboration of the albuminous jelly deposited around the egg in
transit through the oviduct.


1. Inanition
K. Determinative Tests for Pregnancy  
 
In the immature female mammal continued underfeeding results in general
retardation of sexual development. The younger follicles may develop, but
the later stages of follicular development are repressed. In the adult female,
inanition produces marked follicular degeneration and atresia as shown by
many records of retarded sexual development, reduced fertility, even cessation
of the cyclic activities of menstruation and estrus occurring in man and
domestic animals during war-produced or natural famine (Mason in Allen,
Danforth, and Doisy, ’39, p. 1153). The ovary thus seems to be especially
susceptible to starvation conditions, even more so than the testis. As the
condition and well-being of the secondary reproductive structures are dependent upon proper ovarian function, this part of the reproductive system
suffers marked changes as a result of ovarian dysfunction during prolonged
starvation.
 
 
 
Fig. 36. Schematic representation of reproductive organs of the female cat. On the left
side of the illustration, the body of the uterus and uterine horn have been cut open, and
the Fallopian tube and ovary are highly schematized. Observe the partial ovarian capsule
around the ovary shown on the right and the relatively fixed condition of the infundibular
opening of the oviduct lateral to the ovary.
 
 
 
 
Fig. 37. Diagrammatic representation of the reproductive organs of the female rat,
showing the bursa ovarica around each ovary. Observe that uteri open directly into the
vagina. (Modified from Turner, ’48.)
 
Fig. 38. Diagrammatic representation of reproductive structures of the female frog.
Observe that the ostium of the oviduct is not an open, mouth-like structure. It remains
constricted until the egg starts to pass through.
 
 
2. Vitamins
 
a. Vitamin A
 
The ovary is not immediately sensitive to a lack in vitamin A in the diet
but general epithelial changes in the reproductive tract occur which may aid
in producing sterility (Mason, ’39).
 
b. Vitamin B
 
Ovarian and uterine atrophy occur as a result of deficiency of this vitamin
in monkey, rabbit, mouse and rat (Mason, ’39). This effect may be mediated,
at least partly, through the effect of B-deficiency upon the pituitary gland.
 
c. Vitamin C
 
During the earlier stages reproductive activity is maintained, but advanced
stages of C-deficiency produce regressive effects (Mason, ’39).
 
 
 
d. Vitamin E
 
E-deficiency in the female rat does not upset the ovarian and general reproductive behavior. However, established pregnancies are disturbed and are
terminated by resorption of the embryo (Mason, ’39). In the domestic fowl,
unless sufficient amount of vitamin E is present in the egg, embryonic death
occurs during early incubation periods of the egg.
 
3. The Hypophysis (Pituitary Gland)
 
The ovaries experience pronounced atrophy as a result of hypophysectomy
in mammals and non-mammalian species. The earlier stages of follicle formation in the higher mammalian ovary up to the stage of beginning antrum
formation are not so much affected, but later follicular development and interstitial tissue growth are inhibited (Smith, P. E., ’39). (See fig. 40.)
 
===E. Activities of the Ovary in Producing the Reproductive State===
 
====1. The Ovary as a "Storehouse"of Oogonia====
 
The cortex of the ovary contains many young ova in various stages of development. In the human ovary shortly after birth, the number of oogonia
in the cortex of each ovary has been estimated to reach a number as high
as 300,000. This figure should not be taken too literally, as the amount of
variability in the ovary from time to time is great and degeneration of ova
is a common episode. Haggstrdm (’21 ) estimated that each ovary of a 22-yearold woman contained 200,000 young ova. In the ovaries of young rats, Arai
(’20, a and b) estimated that there were on the average around 5,000 ova
under 20 /x in diameter.
 
Without entering into the controversy (Chap. 3) relative to the rhythmic
origin of germ cells in the ovary, one must accept the conclusion that the
normal ovary has within it at all times during its reproductive life large numbers of oogonia in various stages of development. Thus the ovary, aside from
its other activities, functions as a storehouse and nursery for young oogonia.
Relatively few of these oogonia develop into mature eggs in the mammals.
For example, the reproductive life of the human female occurs from about
the age of 10 or 14 years to about 48 years. If one egg per monthly cycle
is discharged from the ovary which is functional during that cycle, only about
400 eggs would be matured in this way. The number would be less if pregnancies intervened. If one accepts the figures given by Haggstrom, an enormous number of eggs of the human ovary never reach their potential goal.
Similarly, according to Corner (’43): “The most prolific egg producer among
mammals, the sow, might possibly shed a total of 3,000 to 3,500 eggs, allowing ten years of ovarian activity not interrupted by pregnancy, and assuming
the very high average of 20 eggs at each three weekly cycle, but she has vastly
more than this in the ovaries at birth.”
 
 
====2 . Position Occupied by the Primitive Female Germ Cells in the Ovarian Cortex====
 
Within the cortex the definitive germ cells or oogonia are found in or near
the germinal epithelium (figs. 39, 64). Some authors regard the oogonium
as originating from the cells of the germinal epithelium. (See Chap. 3, section
on “germ cell origin.”) The definitive germ cell soon becomes associated
with small epithelial cells (fig. 41). This complex of a germ cell with its
associated epithelial cells is found somewhat deeper in the cortex, within or
below the tunica albuginea. As the oogonium begins to experience the changes
propelling it toward a state of maturity, it is regarded as an oocyte (Chap. 3).
 
Characteristics of the primitive oocyte are:
# an enlargement of the nucleus,
# changes within the chromatin material of the nucleus pertaining to meiosis (Chap. 3), and
# a growth and increase in the cytoplasmic substances (fig. 41).
 
 
 
Fig. 40. Effects produced by hypophysectomy on the rat ovary and of replacement
therapy utilizing injections of pituitary gonadotrophins. (After Evans, Simpson, and
Penchaez: Symposia of Quantitative Biology, Vol. 5, 1937. The Biological Laboratory,
Cold Spring Harbor, L. 1., N. Y.) (A) Ovary of hypophysectomized animal. Observe
 
that Graafian follicles are small. They do not proceed further in their development than
the beginning of antral vacuole formation unless replacement therapy is applied. (B)
Ovarian condition of hypophysectomized animal receiving replacement therapy in the
form of injections of the LH (ICSH) gonadotrophic factor of the anterior lobe of the
hypophysis. Interstitial tissue is well developed. (C) Ovarian condition of hypophysectomized animal receiving the FSH gonadotrophic factor. Note follicular growth and antral
vacuole formation; interstitial tissue between the follicles remains somewhat deficient.
(D) Ovarian condition of hypophysectomized animal receiving injections of FSH plus
LH. Corpora lutea are evident (as well as enlarged follicles not shown in the figure).
Interstitial tissue remains deficient.
 
 
 
Fig. 41. Development of primary condition of the Graafian follicle in the opossum
ovary. (A) Young oocyte with associated epithelial (granulosa) cells which in (B)
have encapsulated the oocyte. (C) Encapsulating granulosa cells have increased in
number and are assuming a cuboidal shape. (D) Fully developed condition of the
primary Graafian follicle. Cf. secondary condition shown in fig. 42.
 
 
 
Fig. 42. Secondary conditions of the Graafian follicle in the opossum ovary. Cf. that of the rat ovary in fig. 40.
 
 
As these changes are initiated, the associated epithelial cells increase in
number and eventually encapsulate the oocyte (fig. 41B). This complex of
the oocyte with its surrounding layer of follicle cells is known as an egg follicle.
 
====3. Primary, Secondary, and Tertiary Follicles of de Graaf====
 
In the mammalian ovary the developing egg with its associated cells is
called the Graafian follicle, so named after the Dutch scientist, Reinier de
Graaf (fig. 1), who first described this structure in mammals in 1672-1673.
De Graaf was in error, partly, for he believed that the whole follicular complex was the egg. The mammalian egg as such was first described in 1827 by Karl Ernst von Baer (1792-1876). The following statement is taken from
de Graaf relative to egg follicles.
 
We may assert confidently that eggs are found in all kinds of animals, since
they may be observed not only in birds, in fishes, both oviparous and viviparous,
but very clearly also in quadrupeds and even in man himself. Since it is known to
everyone that eggs are found in birds and fishes, this needs no investigation; but
also in rabbits, hares, dogs, swine, sheep, cows, and other animals which we have
dissected, those structures similar to vesicles exhibit themselves to the eyes of the
dissectors like the germs of eggs in birds. Occurring in the superficial parts of
the testicles, they push up the common tunic, and sometimes shine through it, as
if their exit from the testis is impending. (See fig. 48; also Corner, ’43, page 128.)
 
The mammalian egg with a single layer of epithelial cells surrounding it
is known as a primary Graafian follicle (fig. 41B-D). As the egg and follicle
grow, the number of epithelial cells increase and eventually there are several
 
 
 
Fig. 43. Tertiary conditions of the Graafian follicle in the opossum ovary. Similar conditions are found in other mammalian ovaries. (A) Follicle in which the antral vacuoles
are beginning to form. (B) This is a follicle in which the antral vacuoles are more
numerous and are beginning to coalesce. (C) Condition of the Graafian follicle in the
opossum ovary approaching maturity. Observe that the antral space is large and is filled
with fluid, the liquor folliculi, while the egg and its surrounding cumulus cells are located
at one end of the follicle. The thecal tissue around the follicle is well developed.
 
 
 
 
Fig. 44. Cellular wall of the mature Graafian follicle in the opossum.
 
layers of epithelial or granulosa cells surrounding the egg. It may now be
regarded as a secondary Graafian follicle (fig. 42 A, B). When a stage is reached
where the granulosa cells form a layer five to seven or more cells in thickness
extending outward from the egg to the forming thecal layers, small antral
vacuoles begin to appear among the granulosa cells. The latter follicle, which
is capable of forming antral vacuoles, may be regarded as a tertiary Graafian
follicle (fig. 43A).
 
====4. Hormonal Factors Concerned with the Development of Egg Follicles====
 
The ovary with its contained egg follicles is greatly affected by the gonadotrophic hormones produced in the pituitary body. The removal of the pituitary body (hypophysectomy) causes profound regression of the ovary and
accessory reproductive structures. Accordingly, the response of the ovarian
tissues to these hormonal substances produced by the hypophysis is responsible
for development of the Graafian follicle beyond the early tertiary stage. (See
fig. 40 A.) The relationships between the pituitary hormones and the ovary
have been studied most intimately in the mammals; the pituitary and eggfollicle relationship in lower vertebrates is more obscure, and probably varies
with the particular group.
 
a. Effects Produced by the Gonadotrophic Hormones on the Development of the Mammalian Egg Follicle
 
The follicle-stimulating hormone, FSH, appears to increase the number
of oogonia and to aid the growth and differentiation of the older follicles. It
is possible that some of the effects of FSH upon follicular growth are mediated through its ability, together with small amounts of the luteinizing hormone, LH (ICSH), to cause the formation of estrogen or the female sex hormone, although some investigators believe that estrogen production depends mainly upon the action of LH (ICSH). (See Evans and Simpson in
Pincus and Thimann, ’50, p. 355.) In harmony with the idea that estrogen
is involved in follicular growth there is some evidence which suggests that
introduction of estrogens into the peritoneal cavities of fishes and mammals
results in a stimulation of mitotic activity in the germinal epithelium of the
ovary. It also has been shown that estrogenic substances retard ovarian atrophy
in hypophysectomized immature rats.
 
When the Graafian follicles of the mammalian ovary reach the proper
morphological and physiological conditions (i.e., when they reach the tertiary
follicular stage) an increased sensitivity of the follicle cells to FSH occurs.
As a result, antral vacuoles filled with fluid appear among the granulosa cells;
these eventually coalesce and form the large antral cavity typical of the
mature Graafian follicle of the mctatherian and eutherian mammal (fig. 43).
The presence of LH (ICSH) is necessary to augment the action of FSH
during the latter part of follicle development. The beneficial action of FSH
and LH together in later follicular development is shown by the fact that the
injection of pure FSH alone is incapable of stimulating growth of the follicle
to its full size or to initiate an increased secretion of estrogen. LH aids the
maturing process of the follicle only when present in very minimal amounts
during the early stages of follicle development and in larger amounts during
the later stages of follicular growth. Large amounts of LH in the earlier phases
of the follicle’s development bring about a premature luteinization of the
follicle with ultimate atresia. A proper quantitative balance of these hormones,
therefore, is necessary, with FSH being in the ascendency during the earlier
phases of follicle development, followed by increased amounts of LH with
decreasing amounts of FSH as the follicle reaches maturity (figs. 22, 53, 59).
(For references, consult Evans and Simpson, ’50; Turner, ’48.)
 
h. Stimulating Effects of the Pituitary Gonadotrophins on the Ovaries of Other Vertebrates
 
The hormonal control of the developing follicle of other vertebrate ovaries
follows similar principles to those outlined above for the mammalian ovary,
although data obtained from studies upon other vertebrates in no way compares with the large quantity of information obtained in mammalian studies.
In the hen, FSH and LH injected together cause a rapid development of the
follicles and premature discharge of the egg from the ovary (Fraps, Olsen,
and Neher, ’42). However, in the pigeon. Riddle (’38) reports that another
pituitary hormone, prolactin, appears to decrease the production of these
hormones and stops egg production with a subsequent atrophy of the ovary.
This may be a special means which reduces the number of eggs laid at each
nesting period. In regard to accessory reproductive structures, an estrogenic
hormone is produced in the ovary of the hen which has profound stimulating effects upon the growth of the oviduct (Romanoff and Romanoff, ’49, pp.
242-244). In the frog, Rana pipiens, mammalian pituitary gonadotrophins
are able to effect ovulation (Wright and Hisaw, ’46). Pituitary gonadotrophins
have been shown also to have profound stimulative effects on the ovaries of
fishes, salamanders, and reptiles.
 
====5. Structure of the Vertebrate, Mature Egg Follicle====
 
As a result of the differentiation and growth induced by the gonadotrophic
hormones of the anterior lobe of the hypophysis described in the preceding
paragraphs, the egg follicle reaches a state of maturity (fig. 43C). This state
is achieved when the follicle is about to rupture with the resultant discharge
of the egg. The size of the mature egg follicle varies greatly in different metatherian and eutherian mammals, although the size of the follicle is not related
to the size of the egg. On the other hand the size of the mature egg follicle
in prototherian mammals and in other vertebrate species shows great divergences, being dependent in this group upon the size of the egg at the time
of ovulation (fig. 46).
 
a. Structure of the Mature Follicle in Metatherian and Eutherian
Mammals"'^
 
The structural pattern of the mature Graafian follicle in the human is
strikingly similar to the follicles in other members of this group. It is a vesicular
structure with a diameter approximating five millimeters. Externally, the follicle is composed of two connective-tissue layers, an inner cellular layer containing blood capillaries, the theca interna, and an external, fibrous layer,
the theca externa (figs. 43C, 44). These two layers are not clearly separable.
Passing inward from the theca interna is the basement membrane. Resting
upon this membrane are several layers of epithelial cells comprising the
membrana granulosa. The latter membrane borders the cavity or antrum of
the follicle, which is filled with the liquor folliculi. This liquid is under considerable pressure in the follicle at the time of egg discharge or ovulation.
 
Projecting inward into the antrum on one side is a small, mound-like
mass of granulosa cells, the cumulus oophorus (fig. 43C). Within this hillock
of epithelium, is the egg, which measures in the human about 130 /x to 140 fx
in diameter. In the opossum, the fully developed Graafian follicle is about
1.25 by 2 mm. in diameter, while the slightly oval egg approximates 120 by
135 ii. The egg of the rat and mouse is small, having a diameter of 75 ju,
while that of the dog is about 140 /x; sow, 120 to 140 /x; rabbit, 120 to 130 /x;
monkey, 110 to 120 /x; deer, 115 /x; cat, 120 to 130 (x\ mare, 135 /x; armadillo, 80 /X (Hartman, ’29).
 
* According to Strauss, ’39, the mature Graafian follicle of Erkulus is not a vesicular
structure, as in other higher mammals, but is filled with a loose meshwork of granulosa
cells.
 
 
 
While one Graafian follicle in only one ovary is generally developed in
the human, monkey, cow, ewe, elephant, etc., at each reproductive period,
a multiple condition is found in many other mammals. Each ovary in the
opossum may ripen seven or more follicles, in the bitch (female dog) from
2 to 7 follicles, and in the sow from 4 to 10 follicles at each reproductive period.
 
b. Structure of the Prototherian Egg Follicle
 
The follicle of the prototherian mammals contains a relatively large egg,
while the surrounding fluid and follicular tissue in comparison is small in
quantity (fig. 46). In these mammals the egg fills most of the follicular cavity,
with the exception of a small fluid-filled space intervening between it and
the zona pellucida which lies contiguous to the granulosa cells. Internal and
external thecal tissues surround the granulosa cells as in the Graafian follicle
of the higher mammals.
 
c. Egg Follicles of Other Vertebrates
 
The fully-developed egg follicle in most vertebrates is similar to that found
in the prototherian mammals in that the egg tends to fill the entire follicle.
The general structural relationships also are similar (figs. 45, 47).
 
====6. Ovulatory Process; Possible Factors Controlling Ovulation====
 
The following description of the ovulatory process in the mammal and in
other vertebrates should not be construed as a description of the mechanism,
as the exact mechanism is unknown. However, a certain amount of general
information has been obtained concerning ovulation and the factors involved.
Much of this information has been obtained from studies of the ovulatory
 
 
 
Fig. 45. (A) Young egg follicle of Cryptobranchus alleganiensis, a urodele. (From
Noble: “Biology of the Amphibia,” New York, McGraw-Hill, after Smith.) (B) Diagrammatic representation of ovarian events in the frog resulting in egg discharge. (From Turner: “General Endocrinology,” Philadelphia, W. B. Saunders, slightly modified.)
 
 
Fig. 46. Diagrammatic representation of the egg of the prototherian mammal. Echidna.
 
 
 
Fig. 47. Diagrammatic drawings of the pendent egg follicle in the ovary of the hen.
(A) Low magnification of the entire egg follicle. (B) More detailed view of the blastodisc portion of the egg, nearing maturity, in relation to the pedicle. The latter supports
the follicle and permits the blood vessels to pass into and out of the follicle. Compiled
from sections of the developing ovary of the hen.
 
 
process in higher mammals, especially the rabbit. Among other vertebrates
ovulation in the hen and frog have been the objects of considerable study.
 
a. Process of Ovulation in Higher Mammals
 
1) Changing Tissue Conditions Cuhninating in Egg Discharge from the
Ovary. As the Graafian follicle enlarges and matures under the influence of the follicle-stimulating and luteinizing hormones, it moves closer to the ovarian
surface (fig. 30). The surface of the ovary over the ripening follicle bulges
outward, forming a mound-like protuberance (fig. 30). In the rabbit as shown
by Walton and Hammond (’28) and Hill, Allen, and Cramer (’35) the central part of the original protuberance pushes out still further and forms a
papilla-like swelling (fig. 48A-D). As the papilla develops, it becomes avascuiar, and the underlying tissues become thin and greatly distended. The
tunica albuginea of the ovary and the two thecal layers of the follicle also
are involved in this thinning-out process. As the distended papillary area
continues to grow thinner, a small amount of blood followed by some of the
follicular fluid containing the egg emerges from the follicle and passes into
the surrounding area in close proximity to the infundibulum of the Fallopian
tube (fig. 48 E, F). The entire process is a gradual one and may be described
as gently but not violently explosive (Hill, Allen, and Cramer, ’35). It is of
interest and significance to observe that Burr, Hill, and Allen (’35) were able
to detect a change in electromotive force preceding and during the known
period of ovulation.
 
 
 
 
Fig. 48. Process of ovulation in the rabbit. (A-C) Early external changes of the
surface of the ovary overlying the bulging Graafian follicle. (D) Formation of a secondary papilla. (E) Rupture of the secondary papilla with discharge of egg and follicular fluid, the latter oozing down over ovarian surface of the follicle. (F) Area of
rupture with oozing follicular fluid and egg greatly magnified. (G) Follicle after egg
discharge. (A-E and G, slightly modified from Walton and Hammond, Brit. J. Exp.
Biol., 6; F, modifier from Hill, Allen, and Kramer, Anat. Rec., 63.)
 
 
 
The process of papillary rupture in the rabbit occupies about five seconds;
egg discharge with the surrounding liquor folliculi occurs in approximately
30 to 60 seconds. After the egg has emerged, the follicle as a whole may
collapse. The slit-like opening through which the egg and follicular fluid
passed during ovulation soon is filled with a clot composed of coagulated
blood and follicular fluid (fig. 48G).
 
While the foregoing processes, visible on the ovarian surface, are consummated, certain internal changes occur which form a part of the ovulatory procedure. These changes arc as follows: At about the time the egg is to be
extruded, the follicular fluid reaches its maximum in quantity. This increase
produces considerable follicular turgidity which may be associated with an
endosmotic effect due to an increase in the salt content of the contained fluid.
Shortly before the surface of the follicle ruptures, the cumulus begins to disintegrate, and the egg lies free in the antral fluid. At about this time the first
maturation division of the oocyte occurs in the majority of mammals, and
the first polar body is extruded.
 
Concerning the internal changes accompanying rupture of the mammalian
follicle, passing mention should be made of the theory that bursting blood
vessels discharge their contents into the follicular fluid and thus cause sufficient pressure to rupture the follicle (Heape, ’05). Considerable blood discharge into the follicle seems to be present in some forms, e.g., the mare,
quite absent in others such as the human, and present slightly in the opossum.
 
2) Hormonal Control of the Ovulatory Process. The hormonal mechanism
involved in ovulation in the spontaneously-ovulating mammals probably is as
follows: The follicle-stimulating hormone causes the growth and development
of the follicle or follicles. Estrogen is released by the growing follicles and
possibly by other ovarian tissues due to the presence of small amounts of LH,
and, in consequence, the estrogenic hormone reaches a higher level in the
blood stream (figs. 53; 59).
 
In the meantime, it is probable that the corpus luteum hormone, progesterone, is produced in small amounts. The exact source of this hormone is
not clear. It may be produced by old corpora lutea or by the interstitial tissue of the ovary under the influence of luteotrophin, LTH. The presence of
progesterone, in small quantities together with increasing amounts of estrogen, stimulates the anterior lobe to discharge increased amounts of the luteinizing hormone, LH (ICSH). (See figs. 22, 53, 59.) The elevated level of
estrogen, according to this theory also causes a decreased output of FSH until
it reaches a minimal level at the period shortly before egg discharge (figs.
53, 59). As a result, the increased quantity of LH together with FSH has an
added effect upon the follicle which brings about the chain of events leading
to egg discharge. Evans and Simpson in Pincus and Thimann (’50) give the
proportion of 10 parts of FSH to 1 of LH (ICSH) as the proper hormonal
balance in effecting ovulation in the hypophysectomized rat.
 
In those mammalian species where ovulation is dependent upon the act of
copulation, a nervous stimulus is involved which increases the output from
the pituitary gland of the gonadotrophic factors, particularly LH.
 
b. Ovulation in Vertebrate Groups Other Than the Higher Mammals
 
The physical mechanism involved in the ovulatory procedure in the lower
vertebrate classes is different from that found in higher mammals. Two forms,
the hen and the frog, have been studied in detail. These two animals represent
somewhat different types of ovulatory behavior.
 
1) Hen. As the hen’s egg develops in the ovary, it gradually pushes the
ovarian surface outward; it ultimately becomes suspended from the general
surface of the ovary by means of a narrowing stalk, the pedicle (figs. 31, 47).
When the ovulatory changes are initiated, the musculature of the ovarian
wall overlying the outer surface of the egg appears to contract, and an elongated narrow area along this outer surface becomes avascular. This avascular
area represents the place where the ovarian surface eventually ruptures to
permit the egg to leave the ovary; it is called variously, the rupture area,
stigma, or cicatrix. Gradually, the cicatrix widens and finally a slit-like opening is formed by a tearing apart of tissues in the central region of the cicatrix.
Contractions of the smooth muscle fibers appear to be responsible for this
tearing procedure (Phillips and Warren, ’37). The egg eventually is expelled
through the opening and in many instances it rolls into the infundibular funnel
of the oviduct which at this time is actively engaged in an endeavor to engulf
or “swallow” the egg (fig. 31).
 
2) Frog. The egg of the frog projects into the ovarian cavity within the
ovary and is attached to the ovarian wall by means of a broad area or stalk
(fig. 45B). As the egg enlarges, it tends to push the ovarian surface outward,
and the egg and its follicle thus forms a mound-like protuberance from the
ovarian surface (figs. 45A, B; 72F). The egg and the surrounding ovarian
tissue thus lies exposed on one aspect to the outer surface of the ovary. The
outer surface of exposure is the stigma or area of rupture, and in the older
follicles this area does not contain blood vessels (fig. 72F). As ovulation
approaches, an opening suddenly appears in the area of rupture. The musculature within the theca interna around the follicle then contracts, and the
egg rolls out through the opening in the rupture area like a big ameba (fig.
45B). As the egg passes through the aperture, it may assume an hourglass
shape (Smith, B. G., T6). After the egg is discharged, the follicle contracts
to a much smaller size (fig. 45B). It has been suggested that the rupture of
the external surface of the follicle might be produced by a digestive enzyme
(Rugh, ’35, a and b).
 
3) Hormonal Control of Ovulation in Lower Vertebrates. The hormonal
mechanism regulating ovarian rupture and egg discharge in the lower vertebrate groups has not been as thoroughly explored in all of the vertebrate
groups as it has in the mammals. However, sufficient work has been done to
demonstrate that pituitary hormones are responsible in all of the major vertebrate groups, including the fishes. Amphibian pituitary implants under the
skin or macerated anterior-lobe pituitary tissue injected into the peritoneal
cavity of various amphibia have been effective in producing ovulatory phenomena (Rugh, ’35a). More recently, purified mammalian follicle-stimulating
hormone, FSH, and luteinizing hormone, LH, have been used to stimulate
egg discharge in frog ovarian fragments, as well as in normal and hypophysectomized females. However, the follicle-stimulating hormone alone will not
elicit ovulation (Wright, ’45; Wright and Hisaw, ’46). Accordingly, both
factors are necessary in the frog, as in mammals. In the hen, these two pituitary hormones have been shown to bring about ovulation when injected
intravenously (Fraps, Olsen, and Ncher, ’42; Romanoff and Romanoff, ’49,
pp. 208-215). Also, Neher and Fraps (’50) present evidence which suggests
that progesterone plays a part in the physiological chain which elicits ovulation
in the hen. A close relationship between the physiological procedures effecting
ovulation in the hen and the mammal thus appears to exist.
 
c. Comparison of the Immediate Factors Effecting Egg Discharge in the
 
Vertebrate Group
 
In the vertebrates thus far studied contraction of muscle tissue of the follicle following the rupture of surface tissues presumably is the main factor
which brings about egg expulsion. In higher mammals, associated with muscle
contracture, there also may be an increase in follicular turgidity due to endosmotic phenomena associated with the contained follicular fluid (Walton and
Hammond, ’28). In the frog, hen, and mammal the changes involved in the
surface tissues leading to their rupture are associated with the following sequence of events:
 
( 1 ) avascularity of the surface tissues,
 
(2) a thinning of the surface tissues, and finally
 
(3) a rupture of these tissues.
 
====7. Internal Conditions of the Ovary as an Ovulatory Factor====
 
Internal conditions of the ovary undoubtedly are important in controlling
follicular growth and ovulation. For example, in the Northern fur seal,
Callorhinus ur sinus, the female begins to breed at the age of two years. These
seals travel north once a year to the Pribilof Islands in the Bering Sea where
they go on land to give birth to the single young and also to breed. Most of
the cows arrive between the middle of June and the middle of July. Heavy
with young, the females give birth to their offspring within a few hours or
days after their arrival. Breeding again takes place about six days after parturition. However, lactation continues, and the young are taken care of during
the summer months.
 
Accordingly, these seals mate each year and it appears that for any particular year the mating behavior and ovulation of the egg are controlled by
the ovary, which does not have a corpus luteum. As the corpus luteum, which
forms after ovulation in the site of the Graafian follicle, from which the egg
is discharged, remains intact for a considerable portion of the year, the ovary
which does not have the corpus luteum develops the Graafian follicle for the
next summer period. The following year the other ovary will function, and
so on, alternating each year (Enders, et al., ’46). Thus, the corpus luteum
appears to function as a suppressor of follicular growth within the ovary in
which it lies. In the human female, one ovary functions to produce an egg
one month, while the following month the other ovary ovulates its single egg.
It is possible that here also the large corpus luteum suppresses follicular growth
within the particular ovary concerned.
 
During gestation, the presence of the corpus luteum and its hormone,
progesterone, suppresses follicle growth and ovulation in most of the mammalian group. (The placenta may be the source of progesterone during the
later phases of pregnancy in forms such as the human.) On the other hand,
in the mare, according to Cole, Howell, and Hart (’31 ), ovulation may occur
during pregnancy. Species differences, therefore, exist relative to the control
of ovulation by the corpus luteum and its hormone, progesterone.
 
====8. Number of Eggs Produced by Different Vertebrate Ovaries====
 
The number of eggs produced during the lifetime of the female varies with
the species and is correlated generally with the amount of care given to the
young. In many fishes which experience little or no parental care, enormous
numbers of eggs may be produced, as for example, in the cod where several
millions of eggs are spawned in one season. However, in many of the elasmobranch fishes (i.e., the shark group) the eggs develop within the oviduct,
and the young are born alive. Therefore, only six to a dozen eggs produced
each reproductive period is sufficient to keep the shark species plentiful. In
the hen, where careful breeding and selection have been carried out with a view
to egg production, a good layer will lay from 250 to 300 eggs a year. The deer, moose, fur seal, etc., ovulate one egg per year over a life span of a
few years. As stated previously, the human female might ovulate as many
as 400 eggs in a lifetime. In some species the reproductive life is brief. For
example, in the Pacific salmon (Oncorhynchus) females and males die after
their single spawning season, and a similar demise occurs in the eel (Anguilla).
 
====9. Spontaneous and Dependent Ovulation in the Mammals and in Other Vertebrates====
 
Spontaneous ovulation without apparent stimulation from external sources
occurs commonly throughout the vertebrate series. However, dependent ovulation conditioned by psychic or other nervous stimuli also is found extensively. In certain mammals ovulation has been shown to be dependent upon
the stimulus induced by copulation, as, for example, the ferret, mink, rabbit,
cat, shrew, etc. The stimulus, carried through the nervous system, affects in
some way the anterior lobe of the pituitary gland which then produces increased amounts of LH in addition to FSH. These females experience estrus
spontaneously, but later follicle growth and egg discharge are dependent upon
the added stimulation afforded by copulation.
 
The element of nervous stimulation has a fundamental relationship to the
ovulatory phenomena in the vertebrates. Dependent ovulation occurs in certain birds, such as the pigeon, where mating provides a psychic or nervous
stimulation which effects ovulation. The presence of two eggs in the nest tends
to suppress ovulation. The removal of these eggs will arouse the ovulatory
procedures. However, the pigeon may sometimes lay eggs without the presence
of a male. In wild birds in general, the mating reaction is linked to the
stimulus for egg laying. The hen, on the other hand, is not dependent upon
copulation, but in many of the domestic varieties the presence of a number
of eggs in the nest appears to suppress egg laying. In the lower vertebrates
nervous stimuli also appear to have an influence upon ovulation. The mating
antics of many fish and amphibia may be connected with ovulatory phenomena.
 
====10. Egg Viability after Discharge from the Ovary====
 
The length of time that the egg may survive and retain its capacity for
fertilization after leaving the ovary depends upon the nature of the egg and
its membrane and the surrounding environment. In the urochordate, Styela,
the egg may remain for 3 to 4 hours after it is discharged into the sea water
and still be capable of fertilization. In the elasmobranch fishes, reptiles, and
birds the conditions of the oviduct are such that fertilization must take place
in the upper part of the oviduct within a few seconds or minutes after the
egg reaches the infundibular portion. In Fundulus hetewclitus and possibly
many other teleost fishes, the egg must be fertilized within 15 to 20 minutes
after spawning. In the frog, the egg passes to the uterus at the lower end of
the oviduct shortly after it leaves the ovary. Under ordinary reproductive temperatures which obtain in the spring, the egg may remain there for 3 to 5
days without producing abnormalities. If kept at very cool temperatures,
the period may be extended. Among the mammals the viability after ovulation
varies considerably. In the mare, fertilization must occur within about 2 to 4
hours; rabbit, 2 to 4 hours (Hammond and Marshall, ’25); rat, about 10
hours; mouse, 12 to 24 hours (Long, ’12; Charlton, ’17); opossum, probably
within the first hour or so because of the deposition of the albuminous coating
in the oviduct; fox, probably only a few hours; sow, about 24 hours or less;
man, probably 24 hours or less. In the guinea pig, functional degeneration
may begin within 4 to 8 hours after ovulation (Blandau and Young, ’39) .
 
====11. History of the Egg Follicle after Ovulation====
a. Follicles Which Do Not Develop a Post-ovulatory Body
 
The changes which occur within the egg follicle after the egg has departed
are most variable in different vertebrate species. In most of the fish group
the ovary as a whole shrinks to a fraction of its previous size, and many
very small, immature eggs, interstitial tissue, and collapsed, contracted, empty
follicles make up its composition. Similarly, in frogs, toads, and salamanders
the collapsed follicle which follows ovulation does not develop an organized
structure. The thecal tissue contracts into a small rounded form within which
are a few follicle cells (fig. 45B). These bodies soon disappear.
 
In many snakes and in turtles, the follicle collapses after ovulation, and it
is questionable whether organized bodies develop in the site of the ovulated
follicle. A similar condition appears to be the case in birds. However, Pearl
and Boring (’18) described an abbreviated form of a corpus luteum in the
hen in both discharged and atretic follicles. Also, Rothschild and Traps (’44)
found that the removal of the recently ruptured follicle or of this follicle together with the oldest maturing follicle, at a time when the egg which originated from the ruptured follicle is in the oviduct, retarded the laying of the
egg from 1 to 7 days. Removal of other portions of the ovary in control
hens “practically never” resulted in egg-laying retardation. The ruptured follicle, therefore, is believed, by these investigators, to have some influence on
the time of lay of the egg. Whether the hormone progesterone or something
similar to it may be produced by the ruptured follicle of the hen is questionable, although present evidence appears to suggest that it does (Neher
and Traps, ’50).
 
b. Follicles Which Develop a Post-ovulatory Body; Formation of the
 
Corpus Luteum
 
Post-ovulatory bodies or corpora lutea (yellow bodies) develop in the
ovaries of elasmobranch fishes which give birth to their young alive. Also
in viviparous snakes of the genera Natrix, Storeria, and Thamnophis, it has been shown that the removal of the ovaries with their corpora lutea invariably
results in resorption of the young during the first part of gestation and abortion
of the young during the midgestational period, while their removal during
the close of gestation permits normal birth to occur (Clausen, ’40). The
differentiation of the corpus luteum in the snake involves the granulosa cells
of the follicle and possibly the theca interna. The differentiated organ appears
similar to that of the mammal (Rahn, ’39).
 
The function of the corpus luteum which develops in the site of the ruptured follicle in all mammals, including the Prototheria (fig. 49), has been
the subject of a long series of studies. (See Brambell, ’30, Chap. 9; Corner,
’43, Chap. V.) Its function during the reproductive period of the female
mammal is described below under the section of the ovarian hormones.
The events leading to the formation of the corpus luteum in the mammalian
ovary may be described as follows: After the discharge of the egg, the follicle
collapses. The opening of the follicle at the ovarian surface through which
the egg emerged begins to heal. A slight amount of blood may be deposited
within the antrum of the follicle during the ovulation process in some mammals. If so, the follicle in this condition is known as the corpus hemorrhagicum.
 
 
Fig. 49. (A) Luteal cells of the corpus luteum of the opossum. The cellular conditions
in other higher mammals are similar. The centsal core has not yet been invaded and resorbed by the phagocytes accompanying the ingrowing luteal cells and blood vessels. This
central core is composed of coagulated blood, blood cells, and connective tissue fibrils.
(B) Corpus luteum of the platypus (Ornithorhynchiis).
 
 
Then, under the influence of the luteinizing hormone, LH, the granulosa cells
of the follicle and also cells from the theca interna, together with blood capillaries, proliferate and grow inward into the antral space (figs. 22, 30, 49).
Phagocytes remove the blood clot within the antral space if present, during
the inward growth of these structures. As the ingression of cells and capillaries into the follicle continues, the granulosa cells begin to form large, polyhedral lutein cells, while the epithelioid cells of the theca interna form a
mass of smaller cells which resemble the true lutein cells; the latter are formed
in the peripheral area of the corpus luteum and are called paralutein cells.
The small spindle-shaped cells of the theca interna, together with blood capillaries, become dispersed between the lutein cells, forming a framework for
the latter.
 
If the egg is fertilized, the corpus luteum persists and is known as the
corpus luteum of pregnancy; if fertilization does not take place, it is called
the corpus luteum of ovulation. The latter body soon degenerates. Histologically, both types of corpora are identical when first formed. Eventually the
corpus luteum undergoes involution, and its site becomes infiltrated with
connective tissue. The latter structure is sometimes referred to as the corpus
albicans.
 
====12. Hormones of the Ovary and Their Activities in Effecting the Reproductive Condition====
 
The ovary produces two important hormones which have a profound effect
upon the reproductive process. These two hormones are the female sex hormone, estrogen, and the gestational hormone, progesterone.
 
a. Estrogenic Hormone
 
1) Definition and Source of Production. The induction of estrus (see p.
93 ) or conditions simulating this state is a property of a relatively large number
of organic compounds. Because of this estrus-inducing power, they are spoken
of as estrogenic substances or estrogens. Estrogens are widely distributed in
nature. Two of the most potent natural estrogens are estradiol and estrone
(theelin). Both have been extracted from the mammalian ovary and are
regarded as primary estrogenic hormones. The most powerful estrogen is
estradiol, and it is regarded at present as the compound secreted by the ovary.
During pregnancy it also is found in the placenta. These structures are not
the only sources of estrogens, however, for it is possible to extract them from
urine after ovariectomy, and they occur in the urine of males as well as that
of females. The urine of the stallion is one of the richest sources of estrogens,
and the testis contains a high estrogenic content (Pincus and Thimann, ’48,
p. 381 ). Estrogens are found also in various plants, such as the potato, pussy
willow, etc.
 
 
 
The structural formulae of estradiol and of estrone are as follows:
 
OH ()
 
 
 
Estradiol Estrone
 
 
2) The Ovary as the Normal Source of Estrogen in the Non-pregnant
Female. Aside from the fact that estradiol and estrone are readily extracted
from the ovary, certain experiments tend to focus attention on the ovary as
an important site of estrogen production. For example, the removal of the
ovaries of a normal, adult female mammal causes the accessory reproductive
organs to undergo profound atrophy. The administration of appropriate
amounts of estrogen will restore the accessories of such a female to the condition normal for the resting state. (Consult Pincus, ’50, in Pincus and
Thimann, Chap. I.) The injection of follicle-stimulating hormone with small
amounts of the luteinizing hormone into the diestrous (i.e., sexually-resting)
female with intact ovaries results in follicular development within the ovaries,
accompanied by hypertrophy of the accessory reproductive organs to the full
estrous condition (Nelsen and White, ’41 ; Pincus, ’50, in Pincus and Thimann) .
These and similar experiments point to the ovary as the main site of estrogen
formation in the body of the non-pregnant female.
 
The exact structures of the ovary responsible for estrogen elaboration are
not easily determined. Estrogen is found in all parts of the ovary, but certain
observations and experimental results suggest that it is formed in relation
to the follicular tissues and also by the so-called interstitial tissue of the
ovary. For example, when tumors occur within the thecal tissue of the egg
follicle in women who have experienced the menopause, there is often an
accompanying hypertrophy of the accessory organs. This relationship suggests
that thecal gland tissue of the follicle may have the ability to elaborate estrogen (Geist and Spielman, ’43). On the other hand, the normal hypertrophy
of the granulosa cells of the egg follicle during the normal reproductive cycle,
with the presence of follicular fluid containing estrogen in the antral space
of the follicle, points to the granulosa cells as a possible source of estrogen.
Also, it has been observed that tumorous growths of the granulosa cells of
the follicle produce an excess of estrogenic substance (Geist and Spielman,
’43). Thus, these observations point to the granulosa cells of the egg follicle
of the ovary as being capable of estrogen formation. Another possible source
of estrogen secretion in the ovary is the interstitial cells, derived in part
from theca interna tissue and atretic follicles. These cells are large polyhedral
epithelioid cells scattered between the follicles. Their growth appears to be
directly stimulated by the injection of pure luteinizing hormone (LH; ICSH) in hypophysectomized rats (fig. 40). A rapid production of estrogen results
from such injections and this may mean that these cells are involved in
estrogen production within the ovary (Evans and Simpson in Pincus and
Thimann, ’50).
 
In the pregnant female mammal the placenta appears to be a source of
estrogen production (Pincus and Thimann, ’48, p. 380; Turner, ’48, p. 422).
This is suggested by the successful extraction of estrogen from the placenta
of the human and the mare and also by the fact that in these females removal
of the ovaries during the middle or latter phase of gestation does not result
in estrogen diminution in urinary excretion.
 
3) Pituitary Control of Estrogen Formation. The removal of the anterior
lobe of the pituitary gland of the female results in marked atrophy of ovarian
structures (figs. 40, 50) and of the accessory reproductive organs. Replacement therapy (i.e., the injections of the pituitary gonadotrophins, FSH and
LH) produces a normal reconstitution of the ovarian and reproductive duct
tissues, effecting a normal appearance and functioning of these structures
 
 
 
 
Fig. 50. Follicular atresia in guinea pig ovary. (Redrawn from Asdell, ’46.) This atresia
is a sporadic but not uncommon event in the normal ovary of the mammal. However,
after removal of the pituitary gland, marked atresia and degeneration of the more mature
follicles occur. (A) Fragmentation of granulosa cells is shown. (B) Beginning invasion of the antral space by theca interna tissue is depicted. (Cf. fig. 40A.) (C) Late stage of atresia with invasion of the antral space by internal thecal cells.
 
 
 
Fig. 51. Effects of estradiol (estrogen) upon the female genital tract of the opossum.
(After Risman, J. Morphol., 81.) (A) Reproductive tract of an ovariectomized female.
 
(B) Hypertrophied condition of a female experiencing the normal estrous changes. (C)
Reproductive tract of an ovariectomized female injected with estradiol (0.9 mm.) 36
days after the ovaries were removed.
 
 
(fig. 40). This evidence suggests that the pituitary gonadotrophins, FSH and
LH, control the development of the ovary and, through their influence upon
the ovarian tissues, promote the secretion of estrogen with the subsequent
hypertrophy of the female accessory reproductive structures. It is to be observed that it is not at all clear that FSH in pure form is able to elicit estrogen
production without the presence of LH (ICSH). (See Evans and Simpson
in Pincus and Thimann, ’50, p. 355.)
 
4) Effect of Estrogen upon the Female Mammal. The changes in the
mammalian accessory reproductive organs produced by estrogen are marked.
An increase in vascularity and great hypertrophy of the accessory structures
result from its injection into ovariectomized females. (See figs. 51, 52, 53.)
Increased irritability and activity of the accessory structures also occur. This
increased activity appears to be an important factor in the transportation of
sperm upward within the female accessory organs to the region where the
egg awaits the sperm’s arrival.
 
The alterations in behavior of the female as a result of estrogen stimulation
may be considerable. Females actually seek the presence of a male during
the period of strong estrogenic influence. The long journey of the female fur
seal to the mating grounds in the Bering Sea, the bellowing and tireless search
of the cow moose, the almost uncontrollable demeanor of seeking the male
on the part of the female dog or of the cow in “heat” — these are a few illustrations of the regnant power of this stimulant upon the female mammal.
 
 
The culmination of these changes in behavior, resulting in a receptive attitude
toward the male, is reached at about the time when the egg is discharged
from the ovary in many mammalian species. In certain other mammals the
period of heat may precede the ovulatory phenomena.
 
5) Effects of Estrogen in Other Vertebrates. In the hen, estrogenic hormone causes enlargement and functional activity of the oviduct. Estrogenic
substance, when injected into female chicks from the eighteenth to the fortieth
day, causes an enlargement of the oviduct to about 48 times the natural size.
Estrogen also has a profound effect upon the activities of the full-grown hen
and aids in egg production (Romanoff and Romanoff, ’49; Herrick, ’44).
Estrogen has a pronounced effect upon the oviducts of other vertebrate forms.
 
 
b. Progesterone - The Hormone of the Corpus Luteum
 
1) Production of Progesterone. The luteinizing hormone, LH, of the anterior lobe of the pituitary gland is concerned not only with the development of the egg follicle, but also, after ovulation or the discharge of the egg from
the egg follicle, the remaining granulosa cells, and also, some of the theca
interna cells of the follicle are induced by the LH factor to form the corpus
luteum (figs. 30, 49). Corpora lutea also may be induced by estrogens. This,
however, appears to be an indirect stimulus aroused through estrogenic stimulation of the pituitary gland to secrete added amounts of the LH factor (Evans
and Simpson in Pincus and Thimann, ’50, p. 359).
 
 
 
Fig. 52. Characteristic histological changes in the female reproductive tract under the
influence of estrogen and progesterone. (A-C) Vaginal cyclic changes in the rat. In
(A) is shown the condition of the vaginal wall in the diestrus (resting) condition; (B)
shows changes in vaginal wall structure during estrus. Observe cornification of outer layer
of cells; (C) shows vaginal wall tissue immediately following estrus, i.e., during metestrus.
The presence of progesterone tends to suppress the action of estrogen. (After Turner:
General Endocrinology, Philadelphia, Saunders.) (D, E) Cyclic changes of the Fallopian tube of the human female during the reproductive cycle. In (D) is shown the midinterval of the cycle, i.e,, at a time paralleling estrus in mammals in general; (E) shows
the cellular condition of the lining tissue of the Fallopian tube just before menstruation.
In (D) the tissue has responded to the presence of estrogen; (E) effect of progesterone
is shown. (After Maximow and Bloom: A Textbook of Histology, Philadelphia, Saunders.)
(F, G) Cyclic changes in the uterine-wall tissue during the reproductive cycle in the
human female. In (F) is shown general character of the uterine wall during the follicular
phase, i.e., responses to estrogen; (G) shows the general condition of the uterine wall
following ovulation. The uterus is now responding to the presence of progesterone added
to the follicular or estrogenic stimulation. (After Maximow and Bloom: A Textbook of
Histology, Philadelphia, Saunders.)
 
 
 
A further pituitary principle, however, seems to be involved in the functional behavior of the corpus luteum. This principle, referred to as luteotrophin
(LTH), is associated with the lactogenic-hormone complex produced by the
anterior lobe of the pituitary body; it induces the morphologically developed
corpus luteum to secrete progesterone. (Consult Evans and Simpson in Pincus
and Thimann, ’50, pp. 359, 360; Turner, ’48, p. 379, for references.)
 
The structural formula of progesterone is as follows:
 
2) Effects of Progesterone. Progesterone reduces the irritability of the accessory structures and stimulates the mucosa of the uterus to undergo further
development. This increased developmental and functional condition of the
 
 
Fig. 53. Relationship of the pituitary gonadotrophins and ovarian hormones to the developing Graafian follicle and reproductive-duct change in a polyestrous female mammal.
 
The Graafian follicle responds to the pituitary gonadotrophins, FSH and LH, with the
subsequent growth and ultimate rupture of the follicle and ovulation. Ovulation terminates the follicular phase of the cycle. Under the influence of the LH factor the corpus
luteum is established. The latter becomes functional as a result of stimulation by the
luteotrophic (lactogenic) hormone. The progestational hormone (progesterone) then is
elaborated by the luteal cells. The activity of the latter together with estrogen controls
the luteal phase of the cycle.
 
The rising level of estrogen in the blood suppresses FSH secretion, and together possibly with small amounts of progesterone stimulates LH secretion. Estrogen and small
amounts of progesterone also probably stimulate the secretion of large quantities of LTH,
and the latter stimulates the secretion of progesterone from the recently formed corpus
luteum. When the estrogen level falls, FSH again is secreted.
 
When the estrogen level rises, the endometrium of the uterus and vaginal mucosa are
stimulated. The presence of progesterone suppresses vaginal development, but the uterine
mucosa is stimulated to greater activity. Observe that the involution of the endometrial
lining in most mammals is gradual but in primates it is precipitous and violent, resulting
in menstruation (Cf. fig. 59). (The diestrous period on this chart is shown as a relatively brief period compared to the other aspects of the reproductive cycle. However,
it may be very long in females which do not experience a polyestrous condition and in
some species it may last a good portion of a year.) (Compiled from various sources in
the literature. The portion of the chart showing pituitary and gonadal hormonal relationships is based on data obtained from The Schering Corporation, Bloomfield, N. J.)
 
 
accessory reproductive structures added normally to the estrogenic effects
during the reproductive cycle constitutes the luteal phase of the cycle. In this
phase of the cycle the uterine glands elongate and begin secretion, and the
uterus as a whole is prepared for gestation as a result of the action of the
progestational hormone, progesterone, associated with estrogen. (See figs.
53, 59.)
 
===F. Reproductive State and Its Relation to the Reproductive Cycle in Female Vertebrates===
 
The changes in the female reproductive organs resulting in structural growth
and development referred to above (70-74, 85-88) are consummated in the
ability of the female to fulfill the reproductive functions. The phase of the reproductive events characterized by the ability to reproduce is known as the reproductive climax. This period of culmination remains for a brief period, to be
followed by recession and involution once again to a resting condition. This
developmental progression to a state of reproductive climax followed by regression to a resting condition constitutes a cycle of changing events. When
conditions again are right, the cycle is repeated. Each of these cyclic periods
is known as a reproductive or sexual cycle (figs. 53-59). The reproductive
life of all female vertebrates is characterized by this series of cyclic changes.
 
In most vertebrate species, the female experiences one sexual cycle per
year, which corresponds to the seasonal cycle in the male. However, in various
mammals and in certain birds, such as the domestic hen, several or many
reproductive cycles may occur during the year. The male, under these conditions, is a continuous breeder; that is, he produces sperm continuously throughout the year.
 
1. Sexual Cycle in the Female Mammal
a. Characteristics and Phases of the Reproductive Cycle
 
The estrous cycle in mammals is a complex affair composed of a number
of integrated subcycles. The changes occurring in the ovary are called the
ovarian cycle; the cellular changes in the uterine (Fallopian tube) form a
cycle; the responses in the mammary glands constitute the mammary cycle;
the cyclic events in the uterus make up the uterine cycle, while those in the
vagina form the vaginal cycle (figs. 53, 54, 57).
 
The entire estrous cycle may be divided by ovarian changes into two main
phases: the follicular phase and the luteal phase (fig. 53). The former is under
the immediate influence of the enlarging Graafian follicle, which in turn is
stimulated by the follicle-stimulating and luteinizing hormones of the pituitary
gland, with the subsequent production of estrogen. It is probable that the
luteinizing hormone, LH, is mainly responsible for estrogen secretion. (See
Evans and Simpson in Pincus and Thimann, ’50, p. 355.) The luteal phase on the other hand is controlled by the activities of the corpus luteum, which
has replaced the Graafian follicle under the influence of the luteinizing hormone. The production of progesterone by the corpus luteum is effected as
stated previously by the pituitary hormone, luteotrophin (LTH). Ovulation
is the pivotal point interposed between these two phases. The follicular phase
may occur without ovulation, but the true luteal phase of a normal or fertile
reproductive cycle is dependent upon the ovulatory phenomena. Certain luteal
conditions may be elaborated in an anovulatory cycle, but we are here concerned with the normal events of the fertile reproductive cycle.
 
The follicular phase includes that portion of the reproductive cycle known
as proestrus and a considerable part of estrus. Proestrus is the period of
rapid follicular growth and elaboration of the estrogenic substance which
precedes the period of estrus. Estrogen stimulates developmental changes in
the cellular structure of the accessory reproductive organs, particularly the
vagina and the uterus (figs. 52, 53). Estrus represents the climax of the follicular phase. As such, it is a period of sexual receptivity of the male, and,
in spontaneously ovulating forms, of ovulation. During other periods of the
cycle the female is indifferent or even antagonistic to the male. The period
of estrus is often called period of heat, or period of rut. Estrus is followed
by pregnancy if mating is allowed and is successful, or, in many species, by
a period of pscudopregnancy if mating is not permitted or if the mating is
sterile (figs. 53-57). In some animals, such as the dog, pseudopregnancy is
a prolonged normal event even if mating does not occur, continuing over a
period almost as long as that of normal pregnancy (fig. 54). In other animals,
such as the opossum, pseudopregnancy forms but a brief episode.
 
Pseudopregnancy is, generally speaking, intermediate in duration between
that of a normal luteal phase of the cycle and that of gestation. In those female
mammals where it does not occur normally, it is aroused by such procedures
as sucking of the nipples, stimulation of the vagina and cervix by the natural
mating process, or by artificially stimulating these structures. In some forms,
such as the rabbit, pseudopregnancy is aroused by mere handling or even by
sight of a male. (For discussion, see Selye, ’48, p. 813.)
 
The general changes of growth and development of the accessory organs
which occur during pregnancy and pseudopregnancy are controlled largely
by the secretions of the corpus luteum. The conditions thus imposed by the
corpus luteum comprise the luteal or progestational phai^e of the cycle (fig. 57).
 
In most mammals, if pregnancy does not occur, the ovary and accessory organs again gradually return to the sexually-resting condition known
as diestrus (fig. 53). In man and other primates the changes within the uterus
are not gradual but are precipitous, and most of the endometrial lining, together with considerable amounts of blood, is discharged to the outside (figs.
53, 59). This phenomenon is called menstruation. The causes of menstruation
are largely problematical; it is related to the fall of the level of either or both of the ovarian hormones, progesterone and estrogen. Why certain mammals
should experience violent endometrial changes evident in menstruation and
others a gradual involution and resorption is a question for the future. The
general period of change following estrus in a non-fertile cycle is known as
metestrus (fig. 53). In the rat and mouse, metestrus is short, about one or
two days; in the human and opossum it occupies approximately ten days to
two weeks of the cycle; in the dog, about 40 to 50 days, depending upon
the pseudopregnant conditions experienced in different females. The word
anestrus is applied to a prolonged diestrus or sexual quiescence between two
sexual cycles. However, the involution experienced by the sexual organs in
anestrus is somewhat more profound than that prevailing during a brief
diestrus. The term lactational diestrus is used to refer to the prolonged diestrous condition in forms such as the rat, wherein estrus is suppressed in the
mother while suckling the young.
 
The length of the sexual cycle varies with the species. When females of
the rat or mouse are kept away from a male, the estrous or sexual cycle will
repeat itself every 4 to 5 days. In the sow it occurs every 17 to 20 days. In
the opossum there is a prolonged anestrous period during the summer and
autumn months followed by a polyestrous period during the winter and spring
when the estrous cycle reoccurs about every 28 days. In the human female,
the sexual cycle occupies about 28 days, and there arc probably about ten
normal ovulatory cycles in a year. Some human females may have more,
while others experience a slightly smaller number of true ovulatory cycles
per year.
 
Many mammals have one estrous cycle per year. This condition, known as
monestrus, is true of most wild mammals, such as the deer, wolf, fox, moose,
and coyote. In the shrew, mink, and ferret the moncstrous period may be
prolonged if the female is kept away from the male.
 
Various types of polyestrous conditions exist. In the female dog, for example, there are two or three estrous periods per year about 4 to 6 months
apart. In the cat there are several cycles about two weeks apart during the
autumn, winter, and spring. In the domestic sheep there is a polyestrous period
from September to February in which the cycles occur about every 17 days,
followed by an anestrous period from early March to September. In the mare
in North America, estrous cycles of about 19 to 23 days occur from March
to August. In South America the breeding season is reversed, corresponding
to the reversed seasonal conditions south of the equator. In England many
mares breed in autumn and winter (Asdell, ’46).
 
In some mammals estrus may follow immediately after parturition or birth
of the young. This may occur occasionally in the rat. Under normal conditions
in the fur seal, the female lactates and gestates simultaneously. It is not a
common procedure.
 
It should be observed that there are two aspects of the female reproductive cycle of the mammal relative to fertilization or the bringing together of the
male and female reproductive cell. One aspect is the sexual receptivity of
the female; the other is the time of ovulation of the egg. In most female mammals sexual receptivity and ovulation are intimately associated and occur
spontaneously in the cycle; in others the two events may be separated. In
the former group, the development of “heat” and the maturing of the egg
follicle are closely associated, while in the latter the conditions favoring sexual
receptivity or heat are developed considerably in advance of the maturation
of the follicle, as noted in the table below.
 
b. Relation of Estrus and Ovulation in Some Common Mammals
 
 
1) Spontaneously Ovulating Forms (Sexual Receptivity of Male Occurs at
or near Time of Ovulation):
 
 
 
Length of Estrus or Period
of Heat
 
Time of Ovulation
 
Dog
 
True period of heat about
5-10 days in the middle of
a 21 -day estrous period
 
Variable: 1st day; 2nd day; 5th day;
etc., of true period of heat
 
Guinea pig
 
6-1 1 hrs.
 
Views vary: 1-2 hrs. after heat or
estrus begins; 10 hrs. after; at end
of estrus
 
Man
 
Receptivity not always related
to cyclic events
 
12-17 days after onset of preceding menstruation; average around
14th day
 
Mare
 
2-11 days; average length 5-6
days
 
About 1-2 days before end of estrus; best breeding about 3 days
after heat begins
 
Sheep
 
About 36 hrs.
 
Late in estrus or just after estrus
 
 
ends; presumably about 20-36
hrs. after estrus begins
 
 
Sow
 
Silver fox
 
Rat
 
15 days
 
1-5 days; occurs once a year
in February
 
One determination estimates
estrus to be 9-20 hrs.; most
receptive to male about first
 
3 hrs. of heat. Another determination estimates estrus
to be 12-18 hrs.
 
About 1-3 days after onset of estrus
1st or 2nd day of estrus
 
8 -11 hrs. after beginning of heat
 
2) Dependent Ovulatory Forms (Sexual Receptivity (Heatl Occurs Previous to Time of Ovulation);
 
 
Length of Estrus or Period
of Heat
 
Time of Ovulation
 
Cat
 
2-3 days
 
Time of ovulation uncertain but is
 
 
dependent upon copulation
 
 
 
 
 
Length of Estrus or Period
of Heat
 
Time of Ovulation
 
Rabbit (tame)
 
Estrus prolonged indefinitely
during the breeding season
from spring to summer; a
series of different sets of
egg follicles matured; each
series lasts about a week,
then becomes atretic
 
Ovulation 10-14 hrs. after mating
 
Shrew
 
Estrus prolonged
 
About 55 -70 hrs. after mating
 
Ferret
 
Estrus prolonged
 
About 30 hrs. after mating
 
 
If ovulation and subsequent pregnancy are not permitted by mating, ovarian
involution occurs, and an anestrous interlude is established. Anestrus in the
common rabbit, Oryctolagus cuniculus, occurs from October to March, but
is not absolute.
 
 
c. Non-ovulatory (Anovulatory) Sexual Cycles
 
Not all of the cyclic changes referred to above in those species which normally experience spontaneous ovulation are related to definite egg discharge.
Some cycles occur, more or less abortively, without ovulation of the egg. This
may happen in the human or in other mammals, such as the dog and monkey.
Cycles without ovulations are called non-ovulatory cycles. Menstruation may
follow non-ovulatory cycles in the human female.
 
d. Control of the Estrous Cycle in the Female Mammal
 
In the control of a reproductive cycle in the vertebrate animal, three main
categories of factors appear to influence its appearance and course. These are:
 
(1) external environmental factors, such as light and temperature,
 
(2) external factors governing food supply, and
 
(3) internal factors resulting from an interplay of the activities of the pituitary gland, the ovary, general body health, and of the particular
hereditary constitution of the animal.
 
These factors should be considered not alone in terms of the immediate
production of fertile conditions in the parent, but rather, in view of the total
end to be achieved, namely, the production of a new individual of the species.
For example, the reproductive cycle in the deer reaches its climax or estrus
in the autumn after a long period of lush feeding for the mother. The young
are born the next spring amid favorable temperatures, followed by another
period of bountiful food supply for the mother during lactation and for the
fawn as it is weaned. A receding light factor in the late summer and early
fall thus may be correlated with the period of heat, which in turn proves to
be an optimum time of the year for conception with the resulting birth the
following spring. Similarly, light ascendency is a factor in producing fertility in many birds. Here the incubation period for the young is short and a
plentiful supply of food awaits the parents and young when it is needed. In
other words, the factors which induce the onset of the reproductive state
are correlated with the conditions which enhance the end to be achieved,
namely, the production of a new individual.
 
Let us consider next the internal factors which induce the breeding state
in the female mammal. The commonly held theory regarding the pituitaryovarian relationship governing the control of the reproductive periods in the
mammal which ovulates spontaneously is as follows (figs. 53 and 59) :
 
( 1 ) FSH of the pituitary gland stimulates later follicular growth. This factor
probably is aided by small amounts of the luteinizing factor, LH, to
effect an increased production by the ovarian tissues of the estrogenic
hormone. Early follicle growth probably occurs without FSH.
 
(2) Estrogen output by the ovary rises steadily during the period previous
to ovulation.
 
(3) Old corpora lutea or other ovarian tissue possibly secrete minimal
amounts of progesterone under the influence of lutcotrophin, LTH.
 
(4) As the quantity of estrogen rises in the blood stream, it inhibits the
production of FSH and together with small quantities of progesterone,
increases the output of LH from the pituitary gland. This combination
also may cause an increased outflow of the luteotrophic factor.
 
(5) An increased amount of LH aids in effecting ovulation and the subsequent luteinization of the follicle. As the follicle becomes converted
into the corpus luteum, the presence of the luteotrophic factor brings
about the formation of increased quantities of progesterone and maintains for a time the corpus luteum and the functional luteal phase of
the cycle.
 
(6) In those mammals possessing a scries of repeating sexual cycles, it
is assumed that the fall of estrogen in the blood stream after ovulation
suppresses the LH outflow and permits a fresh liberation of FSH
from the anterior lobe of the pituitary gland, thus starting a new cycle.
The lowering of the estrogen level may be particularly and immediately effective in forms such as the rat and mouse, which have a
short metestrus or luteal phase in the estrous cycle.
 
e. Reproductive Cycle in Lower Vertebrate Females
 
While the words estrus, heat, or rut are generally applied to the mammalian
groups, the recurrent periods of sexual excitement in lower vertebrates are
fundamentally the same sort of reaction, although the changes in the reproductive tract associated with ovarian events are not always the same as in
mammals. However, similar cyclic changes in the ovary and reproductive tract
are present in the lower vertebrates, and their correlation with the activities of the pituitary gland is an established fact. Consequently, the words estrus,
rut, sex excitement, and heat basically designate the same thing throughout
the vertebrate series — namely, a period during which the physiology and
metabolism of the parental body is prepared to undertake the reproductive
functions. In this sense, the words estrus, anestrus, heat, etc. also may be
applied to the male as well as to the female when the male experiences periodic expressions of the sexual state.
 
Although the reproductive cycle in all vertebrates represents basically a
periodic development of the reproductive functions, there is a marked difference between the estrous cycle in the female mammal and the reproductive
cycle in most of the other female vertebrates with the exception of viviparous
forms among the snakes, lizards, and certain fishes. This difference is due
to the absence of a true luteal phase in the cycle. The follicular phase and
elaboration of estrogen appears to be much the same in birds, amphibia, and
fishes as in the mammals, but the phase of the cycle governed by progesterone
secretion, associated with a gestational condition in the accessory reproductive
organs, is found only among those vertebrates which give birth to their
young alive.
 
The reproductive cycles in certain vertebrates may be changed by selective
breeding and domestication. For example, the domestic hen is derived from
the wild jungle fowl. The jungle fowl conform to the general stimuli of nature
as do most wild birds, and the reproductive cycle is associated with a particular season of the year. However, domestication and selection by man of
certain laying strains have altered the original hereditary pattern of seasonal
laying. Consequently, good layers will lay eggs over an extended period of
the year, although there is a strong tendency to follow the ancestral plan by
laying most of the eggs during the spring and summer months; during the
fall and winter months, a smaller number of eggs are laid. Some of the varieties of the domestic hen conform more closely to the ancestral condition
than do other strains. Similar changes may be produced in the buffalo, which
in nature breeds in middle to late summer but in captivity has estrous periods
three weeks apart throughout the year (Asdell, ’46).
 
G. Role of the Ovary in Gestation (Pregnancy)
 
1. Control of Implantation and the Maintenance of
Pregnancy in Mammals
 
The ruling power of the ovary over the processes involved in pregnancy
is absolute, particularly during its earlier phases. In the first place, the corpusluteum hormone, progesterone, is necessary to change the uterus already conditioned by the estrogenic hormone into a functionally active state. The latter
condition is necessary for the nutrition and care of the embryo. A second
change which the gestational hormone imposes upon the genital tract of the
female is to quiet the active, irritable condition aroused by the estrogenic
factor. Progesterone thus serves to neutralize or antagonize the effects of
the estrogenic hormone. A placid condition of the uterus must be maintained
during the period immediately following copulation if the fertilized egg is to
be cared for within the uterine structure. Large doses of estrogens injected
into mammals shortly after copulation prevent implantation of the embryo
in all species thus far studied. (See Selye, ’48, p. 822.)
 
A third effect of the presence of progesterone is the inhibition of the
copulatory responses. Immediately following estrus and ovulation, the female
dog will fight off the aggressiveness of the male — an aggressiveness which
she invited a day or two previously. This change in behavior is introduced
by the development of the corpora lutea and the initiation of the luteal phase
of the reproductive cycle. Similar anaphrodisiac changes are sometimes mentioned in the behavior of the human female during the luteal phase of the
cycle. Progesterone injections also inhibit the copulatory responses in the
ferret (Marshall and Hammond, ’44). All of the above-mentioned activities
of progesterone thus inhibit or antagonize the condition aroused by estrogenic
stimulation.
 
However, aside from these immediate metestrous and post-ovulatory changes
in behavior induced by progesterone, one of its most essential aetivities is
concerned with the maintenance of gestation or pregnancy. Ovariectomy or
the removal of the ovaries at any time during the gestational period in the
rat, mouse, and goat results in death and abortion of the embryo. During
the first part of pregnancy in the rabbit, the ovaries must be left intact but
may be removed in the closing phase without endangering the gestational
process. In the human female, and also in the mare, cat, dog, guinea pig,
and monkey, the ovaries may be removed during the latter half of pregnancy
without danger to the offspring. However, ovariectomy performed in the
early stages of pregnancy in these animals, as well as in all other mammals
thus far studied, produces abortion (Pincus, ’36; Selye, ’48, p. 820). The
corpus luteum hormone, therefore, is essential in the early phases of gestation
in all mammals, and it appears to be necessary during most of the pregnant
period in many other mammals.
 
It is highly probable that the placenta takes over the elaboration of progesterone in those mammals where ovariectomy is possible after the first part
of pregnancy has elapsed. In the human female the corpus luteum normally
involutes at about the third month of pregnancy, but progesterone may be
extracted from the placenta after this period.
 
Although certain effects of the estrogenic hormone appear to be neutralized
(or antagonized) by progesterone during the early phases of reproduction,
other effects of estrogen in relation to progesterone are important for the
maintenance of the pregnant condition. In this connection the estrogenic
hormone appears to suppress some of the growth-promoting effects of progesterone. The two hormones thus work together to promote a gradual development of the uterine tissue and maintain a regulated, balanced condition
throughout pregnancy. The placenta, through its ability to elaborate progesterone and estrogen during the latter phases of pregnancy, is an important
feature regulating pregnancy in some mammals.
 
It should be emphasized in connection with the above statements that the
presence of the fertilized egg and its subsequent development in some manner
affects the maintenance of the corpus luteum. The mechanism by which this
influence is conveyed to the ovary is unknown.
 
2. Gestation Periods, in Days, of Some Common Mammals*
 
* Adapted from Asdell, ’46; Cahalane, ’47; Kenneth, ’43.
 
 
Armadillo (Dasypus novemcinctus)
 
150
 
Bear, black (Ursiis americanus)
 
210
 
Bear, polar (Thalarctos maritimus)
 
240
 
Beaver, Canadian (Castor canadensis)
 
94-100
 
Bison (Bison bison)
 
276
 
Cat, domestic (Felis catus)
 
60
 
Cattle (Bos taurus)
 
282
 
Chimpanzee (Pan satyrus)
 
250
 
Deer, Virginian (Odocoileus virginianus)
 
160-200
 
Dog, domestic (Canis familiaris)
 
58-65
 
Donkey, domestic (Eqiius asinus)
 
365-380
 
Elephant (Elephas africanus)
 
641
 
Elephant (Elephas indicus)
 
607-641
 
Elk (A Ices alces)
 
250
 
Ferret (Putorius faro)
 
42
 
Fox, arctic (Alopex lagopus)
 
60
 
Fox, red (Vulpes vulpes and V. fulva)
 
52-63
 
Giraffe (Giraffa Camelopardalis)
 
450
 
Goat, domestic (Capra hircus)
 
140-160
 
Guinea pig (Cavia porcellus)
 
68-71
 
Horse (Equus cabaltus)
 
330-380
 
Man (Homo sapiens)
 
270-295
 
Lion (Felis leo)
 
106
 
Lynx (Lynx canadensis)
 
63
 
Marten, American (Martes americana)
 
267-280
 
Mink (Mustela vison)
 
42-76
 
Mole (Talpa europaea)
 
30
 
Monkey, macaque (Macaca mulato)
 
160-179
 
Mouse, house (Mas rnusculus)
 
20-21
 
Opossum (Didelphis virginiana)
 
13
 
Pig (Sus scrofa)
 
115-120
 
Rabbit (Lepus; Sylvilagus; Oryctolagus)
 
30-43
 
Rats (Various species)
 
21-25
 
Seal, fur (Callorhinus sp.)
 
340-350
 
Sheep, domestic (Ovis aries)
 
144-160
 
Skunk, common (Mephitis mephitis)
 
63
 
Squirrel, red (Tamiasciurus sp.) 30-40
 
Tiger (Felis tigris) 106
 
Whale (Various species) 334-365
 
Wolf (Canis lupus) 63
 
Woodchuck (Marmota monax) 35-42
 
Zebra, mountain (Equus zebra) 300-345
 
 
3. Maintenance of Pregnancy in Reptiles and Other
Vertebrates
 
In certain viviparous species of the genera Storeria, Matrix and Thamnophis,
Clausen (’40) reports that ovariectomy during gestation results in resorption
of the embryo when performed during the earlier phases of gestation and
abortion during the middle of gestation, but during the terminal portion of
pregnancy the process is unaffected and the young are born normally. These
results are similar to those obtained from the rabbit as noted previously.
 
While experimental evidence is lacking in other vertebrate groups which
give birth to the young alive, the evidence obtained from reptilian and mammalian studies suggests that hormones are responsible for the maintenance
of pregnancy. In harmony with this statement, it may be pointed out that
in the viviparous elasmobranch fishes (e.g., sharks) corpora lutea are developed in the ovaries.
 
H. Role of the Ovary in Parturition or Birth of the Young
 
The real factors bringing about parturition are not known, and any explanation of the matter largely is theoretical. However, certain aspects of
the subject have been explored. For example, it was observed above that
progesterone appears to antagonize the action of estrogen with the result
that the uterus stimulated to irritability and contractility under the influence
of estrogen is made placid by the action of progesterone. In harmony with
this action studies have shown that estrogen tends to increase during the
final stages of normal gestation, while progesterone appears to decrease, accompanied by an involution of the corpora lutea. Consequently, the foregoing
facts have suggested the “estrogen theory,” which postulates that activities
of the uterine musculature are increased by the added amounts of estrogen
in the presence of decreasing amounts of progesterone during the latter phases
of pregnancy. In confirmation of this theory, it has been shown that progesterone injected into a pregnant rabbit near the end of the gestation period
will tend to prolong gestation. A second theory of parturitional behavior
assumes that the posterior lobe of the pituitary gland elaborates oxytocin
which induces increased uterine activity, resulting in birth contractions
(Waring and Landgrebe in Pincus and Thimann, ’50). Again, a third concept
emphasizes Ihe possibility that the placenta may produce substances which
bring about contractions necessary for the expulsion of the young (Turner,
’48, p. 428). Oxytocic substances have been extracted from the placenta,
which suggests the validity of this theory.
 
 
Fig. 54. Changes occurring in the reproductive organs and mammary glands of the
bitch during the reproductive cycle. The student is referred to Asdell (’46), pp. 150-156
and Dukes (’43), pp. 678-682, for detailed description and references pertaining to the
data supporting this chart. The gestation period is based upon data supplied by Kenneth
(’43) and the author’s personal experience with dogs.
 
 
Fig. 55. Reproductive and pregnancy cycles in the sow. (Modified from data supplied
by Corner, Carnegie Inst., Washington, pub. 276, Contrib. to Embryol., 13; the parturition
data derived from Kenneth, ’43.)
 
 
The specific functions of the ovary in parturition probably are more pronounced in those forms where it is essential throughout most of the gestational period, such as the viviparous snakes, and among the mammals, such
forms as the opossum, rat, mouse, and rabbit. The waning of corpus-luteum
activity in these species may serve to lower the level of progesterone in the
body and thus permit some of the other factors, such as estrogen or the
pituitary principle, to activate the uterus.
 
Another factor associated with the ovary and parturition is the hormone
relaxin. This substance was first reported by Hisaw and further studied by
this investigator and his associates (Hisaw, ’25, ’29; and Hisaw, et al., ’44).
 
 
 
Fig. 56. Reproductive and pregnancy cycles in the mare. (Parturition period based
upon data supplied by Kenneth (’43); other data supplied by Asdell (’46) and Dukes
(’43).) It is to be noted that the first corpus luteum of pregnancy degenerates after
about 35 days; the second “crop of corpora lutea” (Asdell) degenerate by 150 days. The
ovaries may be removed after 200 days of pregnancy without causing abortion of young.
 
Relaxin aids in the production of a relaxed condition of the pelvic girdle, a
necessity for the formation of a normal birth passageway for the young.
Relaxin somehow is associated in its formation with the presence of progesterone in the blood stream and also with the intact reproductive system.
Relaxin together with estrogen and progesterone establishes a relaxed condition of the tissues in the pubic area of the pelvic girdle.
 
I. Importance of the Ovary in Mammary-Gland Development
and Lactation
 
Estrogen and progesterone together with the lactogenic hormone, luteotrophin, of the pituitary gland are necessary in mammary-gland development.
The entire story of the relationship of these and of other factors in all mammals or in any particular mammal is not known. However, according to one
theory of mammary-gland development and function, the suggestive roles
played by these hormones presumably are as follows (fig. 58): Estradiol and
other estrogens bring about the development of the mammary-gland ducts;
as a result a tree-like branching of the ducts is effected from a simple im
 
 
Fig. 57. Reproductive and pregnancy cycles in the cow. (Parturition period based upon
data supplied by Kenneth (’43), also by Asdell (’46), Other data for chart derived from
Asdell (’46).
 
Three main characteristics of heat or estrous period are evident: (1) A duration of
heat of only about 10 to 18 hours; (2) abundant secretion during heat of a “stringy
mucus,’’ derived from mucoid epithelium of vagina and from sealing plug of cervix when
cow not in estrus (Asdell); and (3) ovulation occurs from 13Vi to 15Vi hours after termination of estrus (Asdell), Variation in time of ovulation may be considerable, from
2 hours before end of estrus to 26 hours after (Asdell).
 
mature pattern established during earlier development (fig. 5 8 A, A', B). The
male mammary gland may remain similar to the condition shown in fig. 58A.
The maturing of the egg follicles within the ovary and the concomitant formation of estrogen which accompanies sexual maturity is linked with the
more complex state of the mammary-gland system shown in fig. 58B.
 
The next step of mammary-gland development is carried out under the
influence of progesterone. Progesterone is necessary for the development
of the terminal glandular tissue or alveoli associated with these ducts (fig.
58C, D). Finally, the pituitary lactogenic hormone (luteotrophin [LTH];
prolactin) stimulates the actual secretion of milk (fig. 58E). Recent research
also has shown that the lactogenic hormone collaborates in some way with
estrogen and progesterone in the development of the mammary-gland tissue.
 
 
 
 
Fig. 58. Mammary gland changes in relation to reproduction. (Figures are a modification of a figure by Corner: Hormones in Human Reproduction, Princeton, Princeton
University Press. The figure in the latter work was based on a figure by C. D. Turner:
Chap. XI of Sex and Internal Secretions, by Allen, et al., Baltimore, Williams & Wilkins,
1939.) Factors involved in mammary gland development and secretion are somewhat as
follows: (A, A') Condition of the young, infantile gland. (B) Development from a
simple, branched, tubular gland of the immature animal (A') into a compound tubular
gland presumably under the direct stimulation of estrogen, according to one theory, or
by the action of estrogen upon the pituitary gland which then releases mammogen I,
producing these changes, according to Turner, et al.: Chap. XI, Sex and Internal Secretions, by Allen, et al., Baltimore, Williams & Wilkins. (C) Transformation of the compound tubular gland into a compound tubulo-alveolar gland under the influence of progesterone, during the first part of pregnancy, or, according to Turner, et al., by the influence
of estrogen plus progesterone which causes the pituitary to release a second mammogen
which produces the alveolar transformation. (D) Effect of the latter part of pregnancy
is to bring about a development of the cells of the acini of the acinous or alveolar system.
The unit shown in (D) represents a simple, branched, acinous gland, in which there are
six alveoli or acini associated with the duct. (E) Affect of parturition is to release the
lactogenic hormone (prolactin; luteotrophin) from the pituitary gland which brings about
milk secretion. During pregnancy the high levels of estrogen presumably inhibit milk
secretion. However, following pregnancy the level of estrogen is lowered permitting
lactogenic-hormone action upon the alveoli of the gland.
 
The removal of the placenta and embryo at any time during gestation permits milk
flow, provided the mammary glands are sufficiently developed. In the human, any remains
of the placenta after birth inhibit milk secretion, probably because the estrogenic hormone
is elaborated by the placental remnants. (See Selye, ’48, p. 829.)
 
In the rabbit, estrogen and progesterone are necessary for the elaboration of the duct
and secretory acini; in the guinea pig and goat, and to some extent in the primates,
including the human female, estrogen alone is capable of producing the development of
the entire duct and acinous system. (See Turner, ’48, p. 430.)
 
 
During pregnancy, the actual secretion of milk is inhibited by the estrogenic
hormone produced by the ovary and the placenta. The role of estrogen as
an inhibitor of lactation is suggested by the fact that, after lactation has started
following normal parturition, it is possible in the cow and human to suppress
milk flow by the administration of estrogens. After parturition, however,
estrogen is no longer present in^sufflcient amounts to suppress the secretion
of milk, and the mammary gland begins to function. (In the fur seal a postpartum estrus with ovulation follows a short time after parturition. However,
the amount of estrogen produced by this reproductive cycle is not sufficient
to curb lactation.) The neurohumoral reflex, or “suckling reflex,” produced
by the sucking young appears to maintain the flow of milk over a period of
time. Probably this reflex causes a continuous discharge of the lactogenic hormone from the anterior lobe of the hypophysis.
 
Another theory of mammary-gland development maintains that estrogen
stimulates the anterior pituitary gland to release mammogen, which causes
development of the duct system, and estrogen plus progesterone induce a
second mammogen which stimulates lobule-alveolar development. The lactogenic hormone produces the actual secretion of milk. The ovary thus assumes considerable importance in controlling the (morphological) development of the mammary glands in mammals, particularly in those forms in
which the functional condition of the ovary is maintained throughout most of the gestational period, e.g., rat, rabbit, dog, etc. In other species, such as
the human, mare, etc., the placenta through its ability to duplicate the production of the ovarian hormones, assumes a role during the latter phase of
pregnancy. (For further details, consult Folley and Malpress in Pincus and
Thimann, ’48; Selye, ’48, pp. 828-832; and Turner, ’48, pp. 428-448.)
 
 
 
Fig. 59. Stages in the reproductive cycle of the human female and its pituitary-ovarianendometrial relationships (Cf. fig. 53). (Compiled from various sources in the literature.)
(a) As shown at the extreme right of the figure, a fall in the level of estrogen and progesterone in the blood stream, either or both, is associated with endometrial necrosis, bleeding, and discharge (menstruation), (b) The lowering of the estrogen level is associated
with a new outflow of the follicle-stimulating hormone (FSH), as shown at the right of
the figure, (c) In the left side of the figure, the influence of FSH induces egg follicles,
probably several, to grow. Antral spaces appear and enlarge. The presence of a small
amount of the luteinizing hormone (LH) together with FSH stimulates the secretion of
estrogen by the ovarian tissues, possibly by the follicles and interstitial tissue between
the follicles, (d) In consequence, the estrogen level rises in the blood stream, and
menstruation subsides by the fourth day. (e) The continued influence of estrogen produces endometrial growth, and probably increases the outflow of LH from the pituitary
(fig. 53). It is probable, also, that the increased estrogen level stimulates a release of
the luteotrophic hormone from the pituitary, which in turn stimulates the formation of
a small quantity of progesterone by either the interstitial tissue of the ovary or in old
corpora lutea. (f) Some of the developing egg follicles degenerate, while one continues
to develop, (g) The elevation of estrogen suppresses the outflow of FSH as indicated
by the heavy broken line to the left, (h) The elevated level of estrogen together possibly
with small amounts of progesterone evokes an increased outflow of LH and LTH as
indicated by the heavy broken line to the right, (i) LH and FSH bring about ovulation
at about the fourteenth day. (j) LH causes development of corpus luteum. (k) LTH
elicits secretion of progesterone by corpus luteum. Possibly some estrogen is secreted
also by corpus luteum. (1) Progesterone and estrogen stimulate added development of
endometrium, (m) In the absence of fertilization of the egg, the corpus luteum regresses,
with a subsequent fall of progesterone and estrogen levels in the blood stream, terminating
the cycle and permitting a new menstrual procedure.
 
 
In the dog or opossum during each reproductive cycle, the mammary glands
are stimulated to grow and may even secrete milk (dog). These changes
closely parallel the ovarian activities, particularly the luteal phase of the cycle.
In the human, functional growth changes occur in pregnancy, but, pending
the events of the ordinary cycle, alterations in the duct system are slight although the breasts may be turgid due to increased blood flow and connectivetissue development.
 
J. Other Possible Developmental Functions Produced by the Ovary
 
As the eggs of the opossum and rabbit travel through the uterine (Fallopian) tube toward the uterus, they are coated with an albuminous, jelly-like
coating. Similar jelly coatings are added to the eggs of the bird, reptile, frog,
toad, and salamander. These coatings or membranes added to the egg as it
travels through the oviduct are known as tertiary egg membranes.
 
In the toad, the secretion of the protective jelly by the oviduct can be
elicited by the lactogenic hormone present in beef pituitary glands. The secretion of the albuminous jelly coatings around the eggs of frogs, salamanders,
reptiles, and birds may be related to this hormone. The formation of the
crop milk of pigeons has been shown by Riddle and Bates (’39) to be dependent upon the presence of the lactogenic hormone.
 
The function of the ovary in influencing the outflow of the lactogenic hormone from the pituitary, if present in the above cases of glandular secretion,
must be an indirect one. Evans and Simpson in Pincus and Thimann (’50)
ascribe the outflow of the “lactogenic hormone (luteotrophic hormone)” of
the mammalian pituitary to estrin produced by the ovary. It is possible that
in the salamanders, frogs, toads, and the birds an indirect ovarian influence
may similarly induce secretion of the lactogenic hormone which in turn governs the elaboration of the albuminous jelly deposited around the egg in
transit through the oviduct.
 
K. Determinative Tests for Pregnancy  


Various tests have been used to determine the probability of pregnancy  
Various tests have been used to determine the probability of pregnancy  
Line 3,677: Line 2,006:




====Bibliography====
===Bibliography===


Arai, H. 1920a. On the postnatal development of the ovary (albino rat) with especial reference to the number of ova.  
Arai, H. 1920a. On the postnatal development of the ovary (albino rat) with especial reference to the number of ova.  
Am. J. Anat. 27:405.  
Am. J. Anat. 27:405.  


. 1920b. On the cause of hypertrophy of the surviving ovary after semispraying (albino rat) and the number  
. 1920b. On the cause of hypertrophy of the surviving ovary after semispraying (albino rat) and the number of ova in it. Am. J. Anat. 28:59.  
of ova in it. Am. J. Anat. 28:59.  


Aronson, L. R. and Holz-Tucker, M. 1949.  
Aronson, L. R. and Holz-Tucker, M. 1949. Ovulation in the mouthbreeding cichlid fish, Tilapid macrocephala (Bleeker). Anat. Rec. 105:568.  
Ovulation in the mouthbreeding cichlid  
fish, Tilapid macrocephala (Bleeker).  
Anat. Rec. 105:568.  


Asdell, S. A. 1946. Patterns of Mammalian Reproduction. Comstock Publishing  
Asdell, S. A. 1946. Patterns of Mammalian Reproduction. Comstock Publishing  
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Brambell, F. W. R. 1930. The Development of Sex in Vertebrates. The Macmillan Co., New York.  
Brambell, F. W. R. 1930. The Development of Sex in Vertebrates. The Macmillan Co., New York.  


Burns, R. K., Jr. 1931. The process of sex  
Burns, R. K., Jr. 1931. The process of sex transformation in parabiotic Amblystoma. II. Transformation from male to female. J. Exper. Zool. 60:339.  
transformation in parabiotic Amblystoma. II. Transformation from male to  
female. J. Exper. Zool. 60:339.  


Burr, H. S., Hill, R. T., and Allen, E.  
Burr, H. S., Hill, R. T., and Allen, E.  

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Nelsen OE. Comparative embryology of the vertebrates (1953) Mcgraw-Hill Book Company, New York.

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Part I The Period of Preparation

Part I - The Period of Preparation: 1. The Testis and Its Relation to Reproduction | 2. The Vertebrate Ovary and Its Relation to Reproduction | 3. The Development of the Gametes or Sex Cells

The Vertetrate Ovary and Its Relationship to Reproduction

A. The Ovary and Its Importance

One of the editions of the treatise on development, “Exercitationes de Generatione Animalium,” by William Harvey (1578-1657) contains a picture of Jupiter on a throne opening an egg from which various animals, including man, are emerging (fig. 25). Upon the egg (ovum) are engraved the words ovo omnia. At the heading of chapter 62 of this work Harvey placed a caption which explains the phrase ex ovo omnia more explicitly. This heading reads: “Ovum esse primordium commune omnibus animalibus” — the egg is the primordium common to all animals. Published in 1651, this statement still maintains its descriptive force.

Many individual animals arise by asexual reproduction, that is, through a process of division or separation from a parent organism. In the phylum Chordata asexual reproduction is found among the Urochordata, where new individuals may arise by budding from a stolon -like base of the parent (fig. 27). This process often is called gemmation, the formation of a new individual by a protrusion of a mass of cells from the parental body followed by its partial or complete separation. It is a prominent method of reproduction among the lower Metazoa, particularly the coelenterates and sponges. Nevertheless, all animal species among the Metazoa ultimately utilize an egg as the primordium from which the new individual arises. Sexual reproduction, generally associated with the fertilization of an egg by a sperm element, appears to be a needful biological process.



Fig. 25. Copy of the engraved title appearing in one edition of Harvey’s dissertation on generation as shown on p. 139 of Early Theories of Sexual Generation by E. J. Cole. Observe the words “ex ovo omnia” upon the egg which Jupiter is opening. Various animals are emerging from the egg.

Fig. 26. Copy of Hartsoeker’s figure of human spermatozoan, containing the homonculus or “little man,” published in 1694. This figure represents a marked preformationist conception of development. However, it is to be noted that Hartsoeker later abandoned the preformationist concept as a result of his studies on regeneration.



True as the general statement made by Harvey may be, it is not clear what is meant by the word ovum or egg. We know certain of its characteristics, but, for the most part, it must be accepted as an accomplished fact enshrouded in mystery. To Harvey the egg was an indefinite, unorganized association of substance plus a “primordial generative principle” (see Cole, F. J., ’30, p. 140), Other minds have conceived of other meanings. Nevertheless, descriptive and experimental embryology has forced the conclusion that the egg, during its development within the ovary, experiences a profound process of differentiation, resulting in the formation of an invisible organization. Although this organization is invisible, it is imbued with an invincibility which, when set in motion at the time of fertilization, drives the developmental processes onward until final fulfillment is achieved in the fully formed body of the adult organism.


Fig, 27. Forms of asexual reproduction in the subphylum Urochordata 9 #

Chordata. (From MacBride: Textbook of Embryology, Vol. 1, Londo/rt', ^

(A) Budding from "stolon of Perophora listeri, from MacBride after (jR) , (C)

Two stages of budding in an ascidian, from MacBride after Pizon


Beyond the fundamental changes effected in the developing egg while in the ovary, the latter structure has still other roles to maintain. Through the mediation of the hormones produced within the confines of the ovarian substance, the female parent is prepared to assume the responsibilities of reproduction. In addition, in many vertebrates the further responsibility of taking care of the young during the embryonic period stems from the hormones produced in the ovary. In some vertebrates, the instinct of parental care of the young after hatching or after birth indirectly is linked to ovarian-pituitary relationships. Because of these profound and far-reaching influences which the ovary possesses in producing the new individual, it must be regarded as the dynamic center of reproduction for most animal species.

B. Preformationism, Past and Present

The above statement relative to the importance of ovarian influences and of the female parent is a position far removed from that held by some in the past. An ancient belief elevated the male parent and his “seed” or semen. As Cole, F. J., ’30, p. 38, so aptly places the thinking of certain learned sources during the 16th century: “The uterus is regarded as the ‘till’d ground for to sow the seeds on’ — a popular idea, based obviously on the analogy with plants, which prevailed long before and after this period. The seed of the male is therefore the chief agent in generation, but cannot produce an embryo without the cooperation of the female, and whether the result is male or female depends on which side of the uterus the seed falls, the time of the year, temperature, and the incidence of menstruation.” Or, in reference to the Leeuwenhoek’s belief in an intangible preformationism, Cole, F. J., ’30, p. 57, states: “He asserts that every spermatic animalcule of the ram contains a lamb, but it does not assume the external appearance of a lamb until it has been nourished and grown in the uterus of the female.” This statement of A. van Leeuwenhoek (1632-1723) was made as a criticism of N. Hartsoeker (1656-1725) whose extreme adherence to a seminal preformationism led him to picture the preformed body of the human individual, the homonculus, encased within the head of the spermatozoon (fig. 26). Hartsoeker, however, later abandoned this idea.

In fairness it should be observed that the egg during these years did not lack champions who extolled its importance. While the Animalculists considered the sperm cell as the vital element in reproduction, the Ovists, such as Swammerdam (1637-80), Haller (1708-77), Bonnet (1720-93) and Spallanzani (1729-99) believed that the pre-existing parts of the new individual were contained or preformed within the egg.


An extreme form of preformationism was advocated by certain thinkers during this period. For example, Bonnet championed the idea of encasement or “emboitement.” To quote from Bonnet:

The term “emboitement” suggests an idea which is not altogether correct. The germs are not enclosed like boxes or cases one within the other, but a germ forms part of another germ as a seed is a part of the plant on which it develops. This seed encloses a small plant which also has its seeds, in each of which is found a plantule of corresponding smallness. This plantule itself has its seeds and the latter bears plantules incomparably smaller, and so on, and the whole of this ever diminishing series of organized beings formed a part of the first plant, and thus arose its first growths. (Cole, ’30, p. 99.)

On the other hand, there were those who maintained that for some animals, neither the sperm nor the egg were important as “many animals are bred without seed and arise from filth and corruption, such as mice, rats, snails, shell fish, caterpillars, moths, weevils, frogs, and eels” (Cole, ’30, p. 38). This concept was a part of the theory of spontaneous generation of living organisms -a theory ably disproved by the experimental contributions of three men: Redi (1626-97); Spallanzani; and Louis Pasteur (1822-95).

Modern embryology embraces a kind of preformationism, a preformationism which does not see the formed parts of the new individual within the egg or sperm but wi.ich does see within the egg a vital, profound, and highly complex physiochemical organization capable of producing a new individual by a gradual process of development. This organization, this selfdetermining mechanism, is resident in the nucleus with its genes and the organized cytoplasm of the fully developed oocyte or egg. However, as shown later, this organization is dependent upon a series of activating agencies or substances for its ultimate realization. Some of these activating substances come from without, but many of them are produced within the developing organism itself.

C. General Structure of the Reproductive System of the Vertebrate Female

1. General Structure of the Ovary

Morphologically, the ovary presents a series of contrasts in the different vertebrate classes. In teleost fishes the size of the ovary is enormous compared to the body of the female (fig. 28), while in the human (fig. 29), cow, sow, etc., it is a small structure in comparison to the adult body. Again, it may contain millions of mature eggs in the ling, cod and conger, during each breeding season, whereas only a single egg commonly is matured at a time in the cow, elephant, or human. During the reproductive season the ovary may assume a condition of striking colored effects as in the bird, reptile, shark, and frog, only to recede into an appearance drab, shrunken, and disheveled in the non-breeding season.


Fig. 28. Dissection of female specimen of the common flounder, Limanda ferruginea. It particularly shows the ovary with its laterally placed ovarian sinus. Observe that the ovary, during the breeding season, is an elongated structure which extends backward into the tail. There are two ovaries, one on either side of the hemal processes of the caudal vertebrae.

Its shape, also, is most variable in different species. In mammals it is a flattened ovoid structure in the resting condition, but during the reproductive phase it may assume a rounded appearance, containing mound-like protrusions. In birds and reptiles it has the general form of a bunch of grapes. In the amphibia it may be composed of a series of lobes, each of which is a mass of eggs during the breeding season, and in teleost and ganoid fishes it is an elongated structure extending over a considerable area of the body.

Regardless of their many shapes and sizes, the ovaries of vertebrates may be divided morphologically into two main types, namely, compact and saccular forms. The compact type of ovary is found in teleost, elasmobranch, cyclostome, ganoid, and dipnoan fishes, as well as in reptiles, birds and mammals. It has the following regions (figs. 30, 31):

  1. the medulla, an inner zone containing relatively large blood and lymph vessels;
  2. the cortex, an area outside of and surrounding the medulla (except at the hilus), containing many ova in various stages of development;
  3. a tunica albuginea or connective-tissue layer surrounding the cortex;

and

  1. the germinal epithelium or the covering epithelium of the ovary.

The germinal epithelium is continuous with the mesovarium, the peritoneal support of the ovary, and the particular area where the mesovarium attaches to the ovary is known as the hilus. Within the mesovarium and passing through the hilus are to be found the blood and lymph vessels which supply the ovary (fig. 30).

The ovary of the teleost fish is a specialized, compact type of ovary adapted to the ovulation of many thousands, and in pelagic species, millions of eggs at one time. It has an elongate hilar aspect which permits blood vessels to enter the ovarian tissue along one surface of the ovary, whereas the opposite side is the ovulating area. In many teleosts the ovulating surface possesses a special sinus-like space or lumen (fig. 28) which continues posteriad to join the very short oviduct. At the time of ovulation the eggs are discharged into this space and move caudally as the ovarian tissue contracts. In other teleosts this ovulatory space is not a permanent structure but is formed only at the time of ovulation. In Tilapia macrocephala, for example, the ovulatory lumen is formed on the side of the ovary opposite the area where the blood vessels enter. The formation of this space at the time of ovulation is described by Aronson and Holz-Tucker (’49) as a rupture of the elastic follicles during ovulation whereupon the follicle walls shrink toward the ovarian midline.


Fig. 29. Diagrammatic representation of a midsagittal section of the reproductive organs of the human female. (Slightly modified from Morris: Human Anatomy, Philadelphia, Blakiston.)


Nelsen1953 fig030.jpg

Fig. 30. Schematic three-dimensional representation of the cyclic changes which occur in the mammalian ovary.


carrying the interstitial tissue and immature ova. This shrinking away of the tissues of the ovary leaves a space between these tissues and the outside ovarian wall. A lumen thus is formed along the lateral aspect of the ovary which is continuous with the oviduct. Many teleosts have two ovaries (e.g., flounder); in others there is but one (e.g., perch).

The amphibia possess a true saccular ovary (fig. 32). It has a cortex and germinal epithelium somewhat similar to the compact ovarian variety, but the area which forms the medulla in the compact ovary is here represented by a large lymph space. During early development, the amphibian ovary is a compact structure, but later there is a hollowing out and disappearance of the compact medullary portion, and the cortical area remains as a relatively thin, peripheral region (Burns, ’31; Humphrey, ’29).

Histologically the vertebrate ovary is composed of two general cellular groups, namely:

(1) germ cells, and

(2) general tissue cells of various kinds, such as epithelium, connective tissue, smooth muscle fibers, and the complex of elements comprising the vascular system of the ovary (figs. 30, 32). Some of the general cells form the so-called interstitial tissue of the ovary.

The germ cells differ from the general cells in that each of them has a latent potency for developing a new individual. This latent condition is converted into active potentiality during the differentiation of the primitive germ cell into the mature egg or ovum.

2. General Structure of the Accessory Reproductive Organs

The accessory reproductive structures of the female vertebrate may be separated into three general types, viz.:

( 1 ) the total absence of or the presence of a pair of short funnel-like structures which convey the eggs from the peritoneal cavity through


Fig. 31 . Three-dimensional representation of the bird ovary together with the funnel portion (infundibulum) of the oviduct. Recently ovulated egg is shown in the process of engulfment by the infundibulum. Various stages of developing eggs are shown.


Fig. 32. Anterior half of the saccular ovary of Necturus maculosus.

an opening into the urogenital sinus and thence to the outside as in cyclostome fishes,

(2) a short sinus-like tube attached to each ovary and to the urogenital sinus or to a separate body opening as in many teleost fishes (fig. 28), and

(3) two elongated oviducal tubes variously modified (figs. 29, 33, 34, 35, 36, 37).

Except in the teleost fishes the cephalic end of each oviduct generally is open and is placed near the ovary but not united directly with it (figs. 29, 33) although in some species, such as the rat, it is united with an ovarian capsule (fig. 37). In some vertebrates the anterior orifice of the oviduct may be located a considerable distance from the ovary, as in frogs, toads, and salamanders. In many vertebrates, as in birds and snakes, there is but one oviduct in the adult.

In some vertebrates the oviduct is an elongated glandular tube, as in certain urodele amphibia (fig. 33) and in ganoid fishes; in others, such as frogs, birds or mammals, it is composed of two main parts: ( 1 ) an anterior glandular structure and (2) a more caudally placed uterine portion. The latter may unite directly with the cloaca, as in the frog (fig. 38) or by means of a third portion, the vaginal canal or vagina located between the uterus and the cloaca, as in elasmobranch fishes, reptiles, and birds, or between the uterus and the external urogenital sinus, as in mammals (figs. 35, 36, 37). The vaginal canal may be single, as in eutherian mammals, or double, as in metatherian mammals (figs. 35, 36). In metatherian (marsupial) mammals it appears that a third connection with the oviducts is made by the addition of a birth passageway. This birth canal represents a secondary modification of a portion of the vaginal canals and associated structures (figs. 34, 35, 114). (See Nelsen and Maxwell, ’42.) One of the main functions of the vagina or vaginal canal is to receive the intromittent organ of the male during copulation.


The anterior opening of the oviduct is the ostium tubae abdominale, a funnel-shaped aperture generally referred to as the infundibulum. In the transport of the egg from the ovary to the oviduct the infundibulum, in many species, actually engulfs and swallows the egg.

The portion of the oviduct anterior to the uterus often is called the convoluted glandular part; it is highly twisted and convoluted in many species. In amphibians, reptiles, birds, and in some mammals the glandular portion


Fig. 33. Diagrammatic representation of the reproductive structures of female urodele,

Necturus maculosus.


Fig. 34. Diagrammatic lateral view of female reproductive system of the opossum, showing pseudo-vaginal birth canal.


Fig. 35. Reproductive structures of female opossum shown from the ventral view. Observe that the ovary and infundibular portion of the Fallopian tube lie dorsal to the horn of the uterus.

functions to secrete an albuminous coating which is applied to the egg during its passage through this region. In amphibians, reptiles, and birds it forms the major portion of the oviduct, but in mammals it is much reduced in size and extent. In the latter group it is referred to as the uterine or Fallopian tube.

The uterus is a muscular, posterior segment of the oviduct. Like the anterior glandular portion of the oviduct, it also has glandular functions, but these are subservient to its more particular property of expanding into an enlarged compartment where the egg or developing embryo may be retained. The protection and care of the egg or of the embryo during a part or all of its development, is the main function of the uterus in most vertebrates. In the frogs and toads, however, this structure seems to be concerned with a “ripening” process of the egg. Large numbers of eggs are stored in the uterine sac of the frog for a period of time before spawning.

Various degrees of union between the uterine segments of the two oviducts are found in mammals. In the primates they fuse to form a single uterine compartment with two anterior uterine tubes (fig. 29). In carnivores, there is a caudal body of the uterus with two horns extending forward to unite with the uterine tubes (fig. 36). In the rat and mouse, the uterine segments may be entirely separate, coming together and joining the single vaginal chamber (fig. 37). In the opossum the uterine segments are entirely separated, joining a dual vaginal canal system posteriorly (figs. 34, 35, 114).


D. Dependency of the Female Reproductive System on General Body

Conditions

1. Inanition

In the immature female mammal continued underfeeding results in general retardation of sexual development. The younger follicles may develop, but the later stages of follicular development are repressed. In the adult female, inanition produces marked follicular degeneration and atresia as shown by many records of retarded sexual development, reduced fertility, even cessation of the cyclic activities of menstruation and estrus occurring in man and domestic animals during war-produced or natural famine (Mason in Allen, Danforth, and Doisy, ’39, p. 1153). The ovary thus seems to be especially susceptible to starvation conditions, even more so than the testis. As the condition and well-being of the secondary reproductive structures are dependent upon proper ovarian function, this part of the reproductive system suffers marked changes as a result of ovarian dysfunction during prolonged starvation.


Fig. 36. Schematic representation of reproductive organs of the female cat. On the left side of the illustration, the body of the uterus and uterine horn have been cut open, and the Fallopian tube and ovary are highly schematized. Observe the partial ovarian capsule around the ovary shown on the right and the relatively fixed condition of the infundibular opening of the oviduct lateral to the ovary.



Fig. 37. Diagrammatic representation of the reproductive organs of the female rat, showing the bursa ovarica around each ovary. Observe that uteri open directly into the vagina. (Modified from Turner, ’48.)

Fig. 38. Diagrammatic representation of reproductive structures of the female frog. Observe that the ostium of the oviduct is not an open, mouth-like structure. It remains constricted until the egg starts to pass through.


2. Vitamins

a. Vitamin A

The ovary is not immediately sensitive to a lack in vitamin A in the diet but general epithelial changes in the reproductive tract occur which may aid in producing sterility (Mason, ’39).

b. Vitamin B

Ovarian and uterine atrophy occur as a result of deficiency of this vitamin in monkey, rabbit, mouse and rat (Mason, ’39). This effect may be mediated, at least partly, through the effect of B-deficiency upon the pituitary gland.

c. Vitamin C

During the earlier stages reproductive activity is maintained, but advanced stages of C-deficiency produce regressive effects (Mason, ’39).


d. Vitamin E

E-deficiency in the female rat does not upset the ovarian and general reproductive behavior. However, established pregnancies are disturbed and are terminated by resorption of the embryo (Mason, ’39). In the domestic fowl, unless sufficient amount of vitamin E is present in the egg, embryonic death occurs during early incubation periods of the egg.

3. The Hypophysis (Pituitary Gland)

The ovaries experience pronounced atrophy as a result of hypophysectomy in mammals and non-mammalian species. The earlier stages of follicle formation in the higher mammalian ovary up to the stage of beginning antrum formation are not so much affected, but later follicular development and interstitial tissue growth are inhibited (Smith, P. E., ’39). (See fig. 40.)

E. Activities of the Ovary in Producing the Reproductive State

1. The Ovary as a "Storehouse"of Oogonia

The cortex of the ovary contains many young ova in various stages of development. In the human ovary shortly after birth, the number of oogonia in the cortex of each ovary has been estimated to reach a number as high as 300,000. This figure should not be taken too literally, as the amount of variability in the ovary from time to time is great and degeneration of ova is a common episode. Haggstrdm (’21 ) estimated that each ovary of a 22-yearold woman contained 200,000 young ova. In the ovaries of young rats, Arai (’20, a and b) estimated that there were on the average around 5,000 ova under 20 /x in diameter.

Without entering into the controversy (Chap. 3) relative to the rhythmic origin of germ cells in the ovary, one must accept the conclusion that the normal ovary has within it at all times during its reproductive life large numbers of oogonia in various stages of development. Thus the ovary, aside from its other activities, functions as a storehouse and nursery for young oogonia. Relatively few of these oogonia develop into mature eggs in the mammals. For example, the reproductive life of the human female occurs from about the age of 10 or 14 years to about 48 years. If one egg per monthly cycle is discharged from the ovary which is functional during that cycle, only about 400 eggs would be matured in this way. The number would be less if pregnancies intervened. If one accepts the figures given by Haggstrom, an enormous number of eggs of the human ovary never reach their potential goal. Similarly, according to Corner (’43): “The most prolific egg producer among mammals, the sow, might possibly shed a total of 3,000 to 3,500 eggs, allowing ten years of ovarian activity not interrupted by pregnancy, and assuming the very high average of 20 eggs at each three weekly cycle, but she has vastly more than this in the ovaries at birth.”


2 . Position Occupied by the Primitive Female Germ Cells in the Ovarian Cortex

Within the cortex the definitive germ cells or oogonia are found in or near the germinal epithelium (figs. 39, 64). Some authors regard the oogonium as originating from the cells of the germinal epithelium. (See Chap. 3, section on “germ cell origin.”) The definitive germ cell soon becomes associated with small epithelial cells (fig. 41). This complex of a germ cell with its associated epithelial cells is found somewhat deeper in the cortex, within or below the tunica albuginea. As the oogonium begins to experience the changes propelling it toward a state of maturity, it is regarded as an oocyte (Chap. 3).

Characteristics of the primitive oocyte are:

  1. an enlargement of the nucleus,
  2. changes within the chromatin material of the nucleus pertaining to meiosis (Chap. 3), and
  3. a growth and increase in the cytoplasmic substances (fig. 41).


Fig. 40. Effects produced by hypophysectomy on the rat ovary and of replacement therapy utilizing injections of pituitary gonadotrophins. (After Evans, Simpson, and Penchaez: Symposia of Quantitative Biology, Vol. 5, 1937. The Biological Laboratory, Cold Spring Harbor, L. 1., N. Y.) (A) Ovary of hypophysectomized animal. Observe

that Graafian follicles are small. They do not proceed further in their development than the beginning of antral vacuole formation unless replacement therapy is applied. (B) Ovarian condition of hypophysectomized animal receiving replacement therapy in the form of injections of the LH (ICSH) gonadotrophic factor of the anterior lobe of the hypophysis. Interstitial tissue is well developed. (C) Ovarian condition of hypophysectomized animal receiving the FSH gonadotrophic factor. Note follicular growth and antral vacuole formation; interstitial tissue between the follicles remains somewhat deficient. (D) Ovarian condition of hypophysectomized animal receiving injections of FSH plus LH. Corpora lutea are evident (as well as enlarged follicles not shown in the figure). Interstitial tissue remains deficient.


Fig. 41. Development of primary condition of the Graafian follicle in the opossum ovary. (A) Young oocyte with associated epithelial (granulosa) cells which in (B) have encapsulated the oocyte. (C) Encapsulating granulosa cells have increased in number and are assuming a cuboidal shape. (D) Fully developed condition of the primary Graafian follicle. Cf. secondary condition shown in fig. 42.


Fig. 42. Secondary conditions of the Graafian follicle in the opossum ovary. Cf. that of the rat ovary in fig. 40.


As these changes are initiated, the associated epithelial cells increase in number and eventually encapsulate the oocyte (fig. 41B). This complex of the oocyte with its surrounding layer of follicle cells is known as an egg follicle.

3. Primary, Secondary, and Tertiary Follicles of de Graaf

In the mammalian ovary the developing egg with its associated cells is called the Graafian follicle, so named after the Dutch scientist, Reinier de Graaf (fig. 1), who first described this structure in mammals in 1672-1673. De Graaf was in error, partly, for he believed that the whole follicular complex was the egg. The mammalian egg as such was first described in 1827 by Karl Ernst von Baer (1792-1876). The following statement is taken from de Graaf relative to egg follicles.

We may assert confidently that eggs are found in all kinds of animals, since they may be observed not only in birds, in fishes, both oviparous and viviparous, but very clearly also in quadrupeds and even in man himself. Since it is known to everyone that eggs are found in birds and fishes, this needs no investigation; but also in rabbits, hares, dogs, swine, sheep, cows, and other animals which we have dissected, those structures similar to vesicles exhibit themselves to the eyes of the dissectors like the germs of eggs in birds. Occurring in the superficial parts of the testicles, they push up the common tunic, and sometimes shine through it, as if their exit from the testis is impending. (See fig. 48; also Corner, ’43, page 128.)

The mammalian egg with a single layer of epithelial cells surrounding it is known as a primary Graafian follicle (fig. 41B-D). As the egg and follicle grow, the number of epithelial cells increase and eventually there are several


Fig. 43. Tertiary conditions of the Graafian follicle in the opossum ovary. Similar conditions are found in other mammalian ovaries. (A) Follicle in which the antral vacuoles are beginning to form. (B) This is a follicle in which the antral vacuoles are more numerous and are beginning to coalesce. (C) Condition of the Graafian follicle in the opossum ovary approaching maturity. Observe that the antral space is large and is filled with fluid, the liquor folliculi, while the egg and its surrounding cumulus cells are located at one end of the follicle. The thecal tissue around the follicle is well developed.



Fig. 44. Cellular wall of the mature Graafian follicle in the opossum.

layers of epithelial or granulosa cells surrounding the egg. It may now be regarded as a secondary Graafian follicle (fig. 42 A, B). When a stage is reached where the granulosa cells form a layer five to seven or more cells in thickness extending outward from the egg to the forming thecal layers, small antral vacuoles begin to appear among the granulosa cells. The latter follicle, which is capable of forming antral vacuoles, may be regarded as a tertiary Graafian follicle (fig. 43A).

4. Hormonal Factors Concerned with the Development of Egg Follicles

The ovary with its contained egg follicles is greatly affected by the gonadotrophic hormones produced in the pituitary body. The removal of the pituitary body (hypophysectomy) causes profound regression of the ovary and accessory reproductive structures. Accordingly, the response of the ovarian tissues to these hormonal substances produced by the hypophysis is responsible for development of the Graafian follicle beyond the early tertiary stage. (See fig. 40 A.) The relationships between the pituitary hormones and the ovary have been studied most intimately in the mammals; the pituitary and eggfollicle relationship in lower vertebrates is more obscure, and probably varies with the particular group.

a. Effects Produced by the Gonadotrophic Hormones on the Development of the Mammalian Egg Follicle

The follicle-stimulating hormone, FSH, appears to increase the number of oogonia and to aid the growth and differentiation of the older follicles. It is possible that some of the effects of FSH upon follicular growth are mediated through its ability, together with small amounts of the luteinizing hormone, LH (ICSH), to cause the formation of estrogen or the female sex hormone, although some investigators believe that estrogen production depends mainly upon the action of LH (ICSH). (See Evans and Simpson in Pincus and Thimann, ’50, p. 355.) In harmony with the idea that estrogen is involved in follicular growth there is some evidence which suggests that introduction of estrogens into the peritoneal cavities of fishes and mammals results in a stimulation of mitotic activity in the germinal epithelium of the ovary. It also has been shown that estrogenic substances retard ovarian atrophy in hypophysectomized immature rats.

When the Graafian follicles of the mammalian ovary reach the proper morphological and physiological conditions (i.e., when they reach the tertiary follicular stage) an increased sensitivity of the follicle cells to FSH occurs. As a result, antral vacuoles filled with fluid appear among the granulosa cells; these eventually coalesce and form the large antral cavity typical of the mature Graafian follicle of the mctatherian and eutherian mammal (fig. 43). The presence of LH (ICSH) is necessary to augment the action of FSH during the latter part of follicle development. The beneficial action of FSH and LH together in later follicular development is shown by the fact that the injection of pure FSH alone is incapable of stimulating growth of the follicle to its full size or to initiate an increased secretion of estrogen. LH aids the maturing process of the follicle only when present in very minimal amounts during the early stages of follicle development and in larger amounts during the later stages of follicular growth. Large amounts of LH in the earlier phases of the follicle’s development bring about a premature luteinization of the follicle with ultimate atresia. A proper quantitative balance of these hormones, therefore, is necessary, with FSH being in the ascendency during the earlier phases of follicle development, followed by increased amounts of LH with decreasing amounts of FSH as the follicle reaches maturity (figs. 22, 53, 59). (For references, consult Evans and Simpson, ’50; Turner, ’48.)

h. Stimulating Effects of the Pituitary Gonadotrophins on the Ovaries of Other Vertebrates

The hormonal control of the developing follicle of other vertebrate ovaries follows similar principles to those outlined above for the mammalian ovary, although data obtained from studies upon other vertebrates in no way compares with the large quantity of information obtained in mammalian studies. In the hen, FSH and LH injected together cause a rapid development of the follicles and premature discharge of the egg from the ovary (Fraps, Olsen, and Neher, ’42). However, in the pigeon. Riddle (’38) reports that another pituitary hormone, prolactin, appears to decrease the production of these hormones and stops egg production with a subsequent atrophy of the ovary. This may be a special means which reduces the number of eggs laid at each nesting period. In regard to accessory reproductive structures, an estrogenic hormone is produced in the ovary of the hen which has profound stimulating effects upon the growth of the oviduct (Romanoff and Romanoff, ’49, pp. 242-244). In the frog, Rana pipiens, mammalian pituitary gonadotrophins are able to effect ovulation (Wright and Hisaw, ’46). Pituitary gonadotrophins have been shown also to have profound stimulative effects on the ovaries of fishes, salamanders, and reptiles.

5. Structure of the Vertebrate, Mature Egg Follicle

As a result of the differentiation and growth induced by the gonadotrophic hormones of the anterior lobe of the hypophysis described in the preceding paragraphs, the egg follicle reaches a state of maturity (fig. 43C). This state is achieved when the follicle is about to rupture with the resultant discharge of the egg. The size of the mature egg follicle varies greatly in different metatherian and eutherian mammals, although the size of the follicle is not related to the size of the egg. On the other hand the size of the mature egg follicle in prototherian mammals and in other vertebrate species shows great divergences, being dependent in this group upon the size of the egg at the time of ovulation (fig. 46).

a. Structure of the Mature Follicle in Metatherian and Eutherian Mammals"'^

The structural pattern of the mature Graafian follicle in the human is strikingly similar to the follicles in other members of this group. It is a vesicular structure with a diameter approximating five millimeters. Externally, the follicle is composed of two connective-tissue layers, an inner cellular layer containing blood capillaries, the theca interna, and an external, fibrous layer, the theca externa (figs. 43C, 44). These two layers are not clearly separable. Passing inward from the theca interna is the basement membrane. Resting upon this membrane are several layers of epithelial cells comprising the membrana granulosa. The latter membrane borders the cavity or antrum of the follicle, which is filled with the liquor folliculi. This liquid is under considerable pressure in the follicle at the time of egg discharge or ovulation.

Projecting inward into the antrum on one side is a small, mound-like mass of granulosa cells, the cumulus oophorus (fig. 43C). Within this hillock of epithelium, is the egg, which measures in the human about 130 /x to 140 fx in diameter. In the opossum, the fully developed Graafian follicle is about 1.25 by 2 mm. in diameter, while the slightly oval egg approximates 120 by 135 ii. The egg of the rat and mouse is small, having a diameter of 75 ju, while that of the dog is about 140 /x; sow, 120 to 140 /x; rabbit, 120 to 130 /x; monkey, 110 to 120 /x; deer, 115 /x; cat, 120 to 130 (x\ mare, 135 /x; armadillo, 80 /X (Hartman, ’29).

  • According to Strauss, ’39, the mature Graafian follicle of Erkulus is not a vesicular

structure, as in other higher mammals, but is filled with a loose meshwork of granulosa cells.


While one Graafian follicle in only one ovary is generally developed in the human, monkey, cow, ewe, elephant, etc., at each reproductive period, a multiple condition is found in many other mammals. Each ovary in the opossum may ripen seven or more follicles, in the bitch (female dog) from 2 to 7 follicles, and in the sow from 4 to 10 follicles at each reproductive period.

b. Structure of the Prototherian Egg Follicle

The follicle of the prototherian mammals contains a relatively large egg, while the surrounding fluid and follicular tissue in comparison is small in quantity (fig. 46). In these mammals the egg fills most of the follicular cavity, with the exception of a small fluid-filled space intervening between it and the zona pellucida which lies contiguous to the granulosa cells. Internal and external thecal tissues surround the granulosa cells as in the Graafian follicle of the higher mammals.

c. Egg Follicles of Other Vertebrates

The fully-developed egg follicle in most vertebrates is similar to that found in the prototherian mammals in that the egg tends to fill the entire follicle. The general structural relationships also are similar (figs. 45, 47).

6. Ovulatory Process; Possible Factors Controlling Ovulation

The following description of the ovulatory process in the mammal and in other vertebrates should not be construed as a description of the mechanism, as the exact mechanism is unknown. However, a certain amount of general information has been obtained concerning ovulation and the factors involved. Much of this information has been obtained from studies of the ovulatory


Fig. 45. (A) Young egg follicle of Cryptobranchus alleganiensis, a urodele. (From Noble: “Biology of the Amphibia,” New York, McGraw-Hill, after Smith.) (B) Diagrammatic representation of ovarian events in the frog resulting in egg discharge. (From Turner: “General Endocrinology,” Philadelphia, W. B. Saunders, slightly modified.)


Fig. 46. Diagrammatic representation of the egg of the prototherian mammal. Echidna.


Fig. 47. Diagrammatic drawings of the pendent egg follicle in the ovary of the hen. (A) Low magnification of the entire egg follicle. (B) More detailed view of the blastodisc portion of the egg, nearing maturity, in relation to the pedicle. The latter supports the follicle and permits the blood vessels to pass into and out of the follicle. Compiled from sections of the developing ovary of the hen.


process in higher mammals, especially the rabbit. Among other vertebrates ovulation in the hen and frog have been the objects of considerable study.

a. Process of Ovulation in Higher Mammals

1) Changing Tissue Conditions Cuhninating in Egg Discharge from the Ovary. As the Graafian follicle enlarges and matures under the influence of the follicle-stimulating and luteinizing hormones, it moves closer to the ovarian surface (fig. 30). The surface of the ovary over the ripening follicle bulges outward, forming a mound-like protuberance (fig. 30). In the rabbit as shown by Walton and Hammond (’28) and Hill, Allen, and Cramer (’35) the central part of the original protuberance pushes out still further and forms a papilla-like swelling (fig. 48A-D). As the papilla develops, it becomes avascuiar, and the underlying tissues become thin and greatly distended. The tunica albuginea of the ovary and the two thecal layers of the follicle also are involved in this thinning-out process. As the distended papillary area continues to grow thinner, a small amount of blood followed by some of the follicular fluid containing the egg emerges from the follicle and passes into the surrounding area in close proximity to the infundibulum of the Fallopian tube (fig. 48 E, F). The entire process is a gradual one and may be described as gently but not violently explosive (Hill, Allen, and Cramer, ’35). It is of interest and significance to observe that Burr, Hill, and Allen (’35) were able to detect a change in electromotive force preceding and during the known period of ovulation.



Fig. 48. Process of ovulation in the rabbit. (A-C) Early external changes of the surface of the ovary overlying the bulging Graafian follicle. (D) Formation of a secondary papilla. (E) Rupture of the secondary papilla with discharge of egg and follicular fluid, the latter oozing down over ovarian surface of the follicle. (F) Area of rupture with oozing follicular fluid and egg greatly magnified. (G) Follicle after egg discharge. (A-E and G, slightly modified from Walton and Hammond, Brit. J. Exp. Biol., 6; F, modifier from Hill, Allen, and Kramer, Anat. Rec., 63.)



The process of papillary rupture in the rabbit occupies about five seconds; egg discharge with the surrounding liquor folliculi occurs in approximately 30 to 60 seconds. After the egg has emerged, the follicle as a whole may collapse. The slit-like opening through which the egg and follicular fluid passed during ovulation soon is filled with a clot composed of coagulated blood and follicular fluid (fig. 48G).

While the foregoing processes, visible on the ovarian surface, are consummated, certain internal changes occur which form a part of the ovulatory procedure. These changes arc as follows: At about the time the egg is to be extruded, the follicular fluid reaches its maximum in quantity. This increase produces considerable follicular turgidity which may be associated with an endosmotic effect due to an increase in the salt content of the contained fluid. Shortly before the surface of the follicle ruptures, the cumulus begins to disintegrate, and the egg lies free in the antral fluid. At about this time the first maturation division of the oocyte occurs in the majority of mammals, and the first polar body is extruded.

Concerning the internal changes accompanying rupture of the mammalian follicle, passing mention should be made of the theory that bursting blood vessels discharge their contents into the follicular fluid and thus cause sufficient pressure to rupture the follicle (Heape, ’05). Considerable blood discharge into the follicle seems to be present in some forms, e.g., the mare, quite absent in others such as the human, and present slightly in the opossum.

2) Hormonal Control of the Ovulatory Process. The hormonal mechanism involved in ovulation in the spontaneously-ovulating mammals probably is as follows: The follicle-stimulating hormone causes the growth and development of the follicle or follicles. Estrogen is released by the growing follicles and possibly by other ovarian tissues due to the presence of small amounts of LH, and, in consequence, the estrogenic hormone reaches a higher level in the blood stream (figs. 53; 59).

In the meantime, it is probable that the corpus luteum hormone, progesterone, is produced in small amounts. The exact source of this hormone is not clear. It may be produced by old corpora lutea or by the interstitial tissue of the ovary under the influence of luteotrophin, LTH. The presence of progesterone, in small quantities together with increasing amounts of estrogen, stimulates the anterior lobe to discharge increased amounts of the luteinizing hormone, LH (ICSH). (See figs. 22, 53, 59.) The elevated level of estrogen, according to this theory also causes a decreased output of FSH until it reaches a minimal level at the period shortly before egg discharge (figs. 53, 59). As a result, the increased quantity of LH together with FSH has an added effect upon the follicle which brings about the chain of events leading to egg discharge. Evans and Simpson in Pincus and Thimann (’50) give the proportion of 10 parts of FSH to 1 of LH (ICSH) as the proper hormonal balance in effecting ovulation in the hypophysectomized rat.

In those mammalian species where ovulation is dependent upon the act of copulation, a nervous stimulus is involved which increases the output from the pituitary gland of the gonadotrophic factors, particularly LH.

b. Ovulation in Vertebrate Groups Other Than the Higher Mammals

The physical mechanism involved in the ovulatory procedure in the lower vertebrate classes is different from that found in higher mammals. Two forms, the hen and the frog, have been studied in detail. These two animals represent somewhat different types of ovulatory behavior.

1) Hen. As the hen’s egg develops in the ovary, it gradually pushes the ovarian surface outward; it ultimately becomes suspended from the general surface of the ovary by means of a narrowing stalk, the pedicle (figs. 31, 47). When the ovulatory changes are initiated, the musculature of the ovarian wall overlying the outer surface of the egg appears to contract, and an elongated narrow area along this outer surface becomes avascular. This avascular area represents the place where the ovarian surface eventually ruptures to permit the egg to leave the ovary; it is called variously, the rupture area, stigma, or cicatrix. Gradually, the cicatrix widens and finally a slit-like opening is formed by a tearing apart of tissues in the central region of the cicatrix. Contractions of the smooth muscle fibers appear to be responsible for this tearing procedure (Phillips and Warren, ’37). The egg eventually is expelled through the opening and in many instances it rolls into the infundibular funnel of the oviduct which at this time is actively engaged in an endeavor to engulf or “swallow” the egg (fig. 31).

2) Frog. The egg of the frog projects into the ovarian cavity within the ovary and is attached to the ovarian wall by means of a broad area or stalk (fig. 45B). As the egg enlarges, it tends to push the ovarian surface outward, and the egg and its follicle thus forms a mound-like protuberance from the ovarian surface (figs. 45A, B; 72F). The egg and the surrounding ovarian tissue thus lies exposed on one aspect to the outer surface of the ovary. The outer surface of exposure is the stigma or area of rupture, and in the older follicles this area does not contain blood vessels (fig. 72F). As ovulation 

approaches, an opening suddenly appears in the area of rupture. The musculature within the theca interna around the follicle then contracts, and the

egg rolls out through the opening in the rupture area like a big ameba (fig. 45B). As the egg passes through the aperture, it may assume an hourglass shape (Smith, B. G., T6). After the egg is discharged, the follicle contracts to a much smaller size (fig. 45B). It has been suggested that the rupture of the external surface of the follicle might be produced by a digestive enzyme (Rugh, ’35, a and b).

3) Hormonal Control of Ovulation in Lower Vertebrates. The hormonal mechanism regulating ovarian rupture and egg discharge in the lower vertebrate groups has not been as thoroughly explored in all of the vertebrate groups as it has in the mammals. However, sufficient work has been done to demonstrate that pituitary hormones are responsible in all of the major vertebrate groups, including the fishes. Amphibian pituitary implants under the skin or macerated anterior-lobe pituitary tissue injected into the peritoneal cavity of various amphibia have been effective in producing ovulatory phenomena (Rugh, ’35a). More recently, purified mammalian follicle-stimulating hormone, FSH, and luteinizing hormone, LH, have been used to stimulate egg discharge in frog ovarian fragments, as well as in normal and hypophysectomized females. However, the follicle-stimulating hormone alone will not elicit ovulation (Wright, ’45; Wright and Hisaw, ’46). Accordingly, both factors are necessary in the frog, as in mammals. In the hen, these two pituitary hormones have been shown to bring about ovulation when injected intravenously (Fraps, Olsen, and Ncher, ’42; Romanoff and Romanoff, ’49, pp. 208-215). Also, Neher and Fraps (’50) present evidence which suggests that progesterone plays a part in the physiological chain which elicits ovulation in the hen. A close relationship between the physiological procedures effecting ovulation in the hen and the mammal thus appears to exist.

c. Comparison of the Immediate Factors Effecting Egg Discharge in the

Vertebrate Group

In the vertebrates thus far studied contraction of muscle tissue of the follicle following the rupture of surface tissues presumably is the main factor which brings about egg expulsion. In higher mammals, associated with muscle contracture, there also may be an increase in follicular turgidity due to endosmotic phenomena associated with the contained follicular fluid (Walton and Hammond, ’28). In the frog, hen, and mammal the changes involved in the surface tissues leading to their rupture are associated with the following sequence of events:

( 1 ) avascularity of the surface tissues,

(2) a thinning of the surface tissues, and finally

(3) a rupture of these tissues.

7. Internal Conditions of the Ovary as an Ovulatory Factor

Internal conditions of the ovary undoubtedly are important in controlling follicular growth and ovulation. For example, in the Northern fur seal, Callorhinus ur sinus, the female begins to breed at the age of two years. These seals travel north once a year to the Pribilof Islands in the Bering Sea where they go on land to give birth to the single young and also to breed. Most of the cows arrive between the middle of June and the middle of July. Heavy with young, the females give birth to their offspring within a few hours or days after their arrival. Breeding again takes place about six days after parturition. However, lactation continues, and the young are taken care of during the summer months.

Accordingly, these seals mate each year and it appears that for any particular year the mating behavior and ovulation of the egg are controlled by the ovary, which does not have a corpus luteum. As the corpus luteum, which forms after ovulation in the site of the Graafian follicle, from which the egg is discharged, remains intact for a considerable portion of the year, the ovary which does not have the corpus luteum develops the Graafian follicle for the next summer period. The following year the other ovary will function, and so on, alternating each year (Enders, et al., ’46). Thus, the corpus luteum appears to function as a suppressor of follicular growth within the ovary in which it lies. In the human female, one ovary functions to produce an egg one month, while the following month the other ovary ovulates its single egg. It is possible that here also the large corpus luteum suppresses follicular growth within the particular ovary concerned.

During gestation, the presence of the corpus luteum and its hormone, progesterone, suppresses follicle growth and ovulation in most of the mammalian group. (The placenta may be the source of progesterone during the later phases of pregnancy in forms such as the human.) On the other hand, in the mare, according to Cole, Howell, and Hart (’31 ), ovulation may occur during pregnancy. Species differences, therefore, exist relative to the control of ovulation by the corpus luteum and its hormone, progesterone.

8. Number of Eggs Produced by Different Vertebrate Ovaries

The number of eggs produced during the lifetime of the female varies with the species and is correlated generally with the amount of care given to the young. In many fishes which experience little or no parental care, enormous numbers of eggs may be produced, as for example, in the cod where several millions of eggs are spawned in one season. However, in many of the elasmobranch fishes (i.e., the shark group) the eggs develop within the oviduct, and the young are born alive. Therefore, only six to a dozen eggs produced each reproductive period is sufficient to keep the shark species plentiful. In the hen, where careful breeding and selection have been carried out with a view to egg production, a good layer will lay from 250 to 300 eggs a year. The deer, moose, fur seal, etc., ovulate one egg per year over a life span of a few years. As stated previously, the human female might ovulate as many as 400 eggs in a lifetime. In some species the reproductive life is brief. For example, in the Pacific salmon (Oncorhynchus) females and males die after their single spawning season, and a similar demise occurs in the eel (Anguilla).

9. Spontaneous and Dependent Ovulation in the Mammals and in Other Vertebrates

Spontaneous ovulation without apparent stimulation from external sources occurs commonly throughout the vertebrate series. However, dependent ovulation conditioned by psychic or other nervous stimuli also is found extensively. In certain mammals ovulation has been shown to be dependent upon the stimulus induced by copulation, as, for example, the ferret, mink, rabbit, cat, shrew, etc. The stimulus, carried through the nervous system, affects in some way the anterior lobe of the pituitary gland which then produces increased amounts of LH in addition to FSH. These females experience estrus spontaneously, but later follicle growth and egg discharge are dependent upon the added stimulation afforded by copulation.

The element of nervous stimulation has a fundamental relationship to the ovulatory phenomena in the vertebrates. Dependent ovulation occurs in certain birds, such as the pigeon, where mating provides a psychic or nervous stimulation which effects ovulation. The presence of two eggs in the nest tends to suppress ovulation. The removal of these eggs will arouse the ovulatory procedures. However, the pigeon may sometimes lay eggs without the presence of a male. In wild birds in general, the mating reaction is linked to the stimulus for egg laying. The hen, on the other hand, is not dependent upon copulation, but in many of the domestic varieties the presence of a number of eggs in the nest appears to suppress egg laying. In the lower vertebrates nervous stimuli also appear to have an influence upon ovulation. The mating antics of many fish and amphibia may be connected with ovulatory phenomena.

10. Egg Viability after Discharge from the Ovary

The length of time that the egg may survive and retain its capacity for fertilization after leaving the ovary depends upon the nature of the egg and its membrane and the surrounding environment. In the urochordate, Styela, the egg may remain for 3 to 4 hours after it is discharged into the sea water and still be capable of fertilization. In the elasmobranch fishes, reptiles, and birds the conditions of the oviduct are such that fertilization must take place in the upper part of the oviduct within a few seconds or minutes after the egg reaches the infundibular portion. In Fundulus hetewclitus and possibly many other teleost fishes, the egg must be fertilized within 15 to 20 minutes after spawning. In the frog, the egg passes to the uterus at the lower end of the oviduct shortly after it leaves the ovary. Under ordinary reproductive temperatures which obtain in the spring, the egg may remain there for 3 to 5 days without producing abnormalities. If kept at very cool temperatures, the period may be extended. Among the mammals the viability after ovulation varies considerably. In the mare, fertilization must occur within about 2 to 4 hours; rabbit, 2 to 4 hours (Hammond and Marshall, ’25); rat, about 10 hours; mouse, 12 to 24 hours (Long, ’12; Charlton, ’17); opossum, probably within the first hour or so because of the deposition of the albuminous coating in the oviduct; fox, probably only a few hours; sow, about 24 hours or less; man, probably 24 hours or less. In the guinea pig, functional degeneration may begin within 4 to 8 hours after ovulation (Blandau and Young, ’39) .

11. History of the Egg Follicle after Ovulation

a. Follicles Which Do Not Develop a Post-ovulatory Body

The changes which occur within the egg follicle after the egg has departed are most variable in different vertebrate species. In most of the fish group the ovary as a whole shrinks to a fraction of its previous size, and many very small, immature eggs, interstitial tissue, and collapsed, contracted, empty follicles make up its composition. Similarly, in frogs, toads, and salamanders the collapsed follicle which follows ovulation does not develop an organized structure. The thecal tissue contracts into a small rounded form within which are a few follicle cells (fig. 45B). These bodies soon disappear.

In many snakes and in turtles, the follicle collapses after ovulation, and it is questionable whether organized bodies develop in the site of the ovulated follicle. A similar condition appears to be the case in birds. However, Pearl and Boring (’18) described an abbreviated form of a corpus luteum in the hen in both discharged and atretic follicles. Also, Rothschild and Traps (’44) found that the removal of the recently ruptured follicle or of this follicle together with the oldest maturing follicle, at a time when the egg which originated from the ruptured follicle is in the oviduct, retarded the laying of the egg from 1 to 7 days. Removal of other portions of the ovary in control hens “practically never” resulted in egg-laying retardation. The ruptured follicle, therefore, is believed, by these investigators, to have some influence on the time of lay of the egg. Whether the hormone progesterone or something similar to it may be produced by the ruptured follicle of the hen is questionable, although present evidence appears to suggest that it does (Neher and Traps, ’50).

b. Follicles Which Develop a Post-ovulatory Body; Formation of the

Corpus Luteum

Post-ovulatory bodies or corpora lutea (yellow bodies) develop in the ovaries of elasmobranch fishes which give birth to their young alive. Also in viviparous snakes of the genera Natrix, Storeria, and Thamnophis, it has been shown that the removal of the ovaries with their corpora lutea invariably results in resorption of the young during the first part of gestation and abortion of the young during the midgestational period, while their removal during the close of gestation permits normal birth to occur (Clausen, ’40). The differentiation of the corpus luteum in the snake involves the granulosa cells of the follicle and possibly the theca interna. The differentiated organ appears similar to that of the mammal (Rahn, ’39).

The function of the corpus luteum which develops in the site of the ruptured follicle in all mammals, including the Prototheria (fig. 49), has been the subject of a long series of studies. (See Brambell, ’30, Chap. 9; Corner, ’43, Chap. V.) Its function during the reproductive period of the female mammal is described below under the section of the ovarian hormones. The events leading to the formation of the corpus luteum in the mammalian ovary may be described as follows: After the discharge of the egg, the follicle collapses. The opening of the follicle at the ovarian surface through which the egg emerged begins to heal. A slight amount of blood may be deposited within the antrum of the follicle during the ovulation process in some mammals. If so, the follicle in this condition is known as the corpus hemorrhagicum.


Fig. 49. (A) Luteal cells of the corpus luteum of the opossum. The cellular conditions in other higher mammals are similar. The centsal core has not yet been invaded and resorbed by the phagocytes accompanying the ingrowing luteal cells and blood vessels. This central core is composed of coagulated blood, blood cells, and connective tissue fibrils. (B) Corpus luteum of the platypus (Ornithorhynchiis).


Then, under the influence of the luteinizing hormone, LH, the granulosa cells of the follicle and also cells from the theca interna, together with blood capillaries, proliferate and grow inward into the antral space (figs. 22, 30, 49). Phagocytes remove the blood clot within the antral space if present, during the inward growth of these structures. As the ingression of cells and capillaries into the follicle continues, the granulosa cells begin to form large, polyhedral lutein cells, while the epithelioid cells of the theca interna form a mass of smaller cells which resemble the true lutein cells; the latter are formed in the peripheral area of the corpus luteum and are called paralutein cells. The small spindle-shaped cells of the theca interna, together with blood capillaries, become dispersed between the lutein cells, forming a framework for the latter.

If the egg is fertilized, the corpus luteum persists and is known as the corpus luteum of pregnancy; if fertilization does not take place, it is called the corpus luteum of ovulation. The latter body soon degenerates. Histologically, both types of corpora are identical when first formed. Eventually the corpus luteum undergoes involution, and its site becomes infiltrated with connective tissue. The latter structure is sometimes referred to as the corpus albicans.

12. Hormones of the Ovary and Their Activities in Effecting the Reproductive Condition

The ovary produces two important hormones which have a profound effect upon the reproductive process. These two hormones are the female sex hormone, estrogen, and the gestational hormone, progesterone.

a. Estrogenic Hormone

1) Definition and Source of Production. The induction of estrus (see p. 93 ) or conditions simulating this state is a property of a relatively large number of organic compounds. Because of this estrus-inducing power, they are spoken of as estrogenic substances or estrogens. Estrogens are widely distributed in nature. Two of the most potent natural estrogens are estradiol and estrone (theelin). Both have been extracted from the mammalian ovary and are regarded as primary estrogenic hormones. The most powerful estrogen is estradiol, and it is regarded at present as the compound secreted by the ovary. During pregnancy it also is found in the placenta. These structures are not the only sources of estrogens, however, for it is possible to extract them from urine after ovariectomy, and they occur in the urine of males as well as that of females. The urine of the stallion is one of the richest sources of estrogens, and the testis contains a high estrogenic content (Pincus and Thimann, ’48, p. 381 ). Estrogens are found also in various plants, such as the potato, pussy willow, etc.


The structural formulae of estradiol and of estrone are as follows:

OH ()


Estradiol Estrone


2) The Ovary as the Normal Source of Estrogen in the Non-pregnant Female. Aside from the fact that estradiol and estrone are readily extracted from the ovary, certain experiments tend to focus attention on the ovary as an important site of estrogen production. For example, the removal of the ovaries of a normal, adult female mammal causes the accessory reproductive organs to undergo profound atrophy. The administration of appropriate amounts of estrogen will restore the accessories of such a female to the condition normal for the resting state. (Consult Pincus, ’50, in Pincus and Thimann, Chap. I.) The injection of follicle-stimulating hormone with small amounts of the luteinizing hormone into the diestrous (i.e., sexually-resting) female with intact ovaries results in follicular development within the ovaries, accompanied by hypertrophy of the accessory reproductive organs to the full estrous condition (Nelsen and White, ’41 ; Pincus, ’50, in Pincus and Thimann) . These and similar experiments point to the ovary as the main site of estrogen formation in the body of the non-pregnant female.

The exact structures of the ovary responsible for estrogen elaboration are not easily determined. Estrogen is found in all parts of the ovary, but certain observations and experimental results suggest that it is formed in relation to the follicular tissues and also by the so-called interstitial tissue of the ovary. For example, when tumors occur within the thecal tissue of the egg follicle in women who have experienced the menopause, there is often an accompanying hypertrophy of the accessory organs. This relationship suggests that thecal gland tissue of the follicle may have the ability to elaborate estrogen (Geist and Spielman, ’43). On the other hand, the normal hypertrophy of the granulosa cells of the egg follicle during the normal reproductive cycle, with the presence of follicular fluid containing estrogen in the antral space of the follicle, points to the granulosa cells as a possible source of estrogen. Also, it has been observed that tumorous growths of the granulosa cells of the follicle produce an excess of estrogenic substance (Geist and Spielman, ’43). Thus, these observations point to the granulosa cells of the egg follicle of the ovary as being capable of estrogen formation. Another possible source of estrogen secretion in the ovary is the interstitial cells, derived in part from theca interna tissue and atretic follicles. These cells are large polyhedral epithelioid cells scattered between the follicles. Their growth appears to be directly stimulated by the injection of pure luteinizing hormone (LH; ICSH) in hypophysectomized rats (fig. 40). A rapid production of estrogen results from such injections and this may mean that these cells are involved in estrogen production within the ovary (Evans and Simpson in Pincus and Thimann, ’50).

In the pregnant female mammal the placenta appears to be a source of estrogen production (Pincus and Thimann, ’48, p. 380; Turner, ’48, p. 422). This is suggested by the successful extraction of estrogen from the placenta of the human and the mare and also by the fact that in these females removal of the ovaries during the middle or latter phase of gestation does not result in estrogen diminution in urinary excretion.

3) Pituitary Control of Estrogen Formation. The removal of the anterior lobe of the pituitary gland of the female results in marked atrophy of ovarian structures (figs. 40, 50) and of the accessory reproductive organs. Replacement therapy (i.e., the injections of the pituitary gonadotrophins, FSH and LH) produces a normal reconstitution of the ovarian and reproductive duct tissues, effecting a normal appearance and functioning of these structures



Fig. 50. Follicular atresia in guinea pig ovary. (Redrawn from Asdell, ’46.) This atresia is a sporadic but not uncommon event in the normal ovary of the mammal. However, after removal of the pituitary gland, marked atresia and degeneration of the more mature follicles occur. (A) Fragmentation of granulosa cells is shown. (B) Beginning invasion of the antral space by theca interna tissue is depicted. (Cf. fig. 40A.) (C) Late stage of atresia with invasion of the antral space by internal thecal cells.


Fig. 51. Effects of estradiol (estrogen) upon the female genital tract of the opossum. (After Risman, J. Morphol., 81.) (A) Reproductive tract of an ovariectomized female.

(B) Hypertrophied condition of a female experiencing the normal estrous changes. (C) Reproductive tract of an ovariectomized female injected with estradiol (0.9 mm.) 36 days after the ovaries were removed.


(fig. 40). This evidence suggests that the pituitary gonadotrophins, FSH and LH, control the development of the ovary and, through their influence upon the ovarian tissues, promote the secretion of estrogen with the subsequent hypertrophy of the female accessory reproductive structures. It is to be observed that it is not at all clear that FSH in pure form is able to elicit estrogen production without the presence of LH (ICSH). (See Evans and Simpson in Pincus and Thimann, ’50, p. 355.)

4) Effect of Estrogen upon the Female Mammal. The changes in the mammalian accessory reproductive organs produced by estrogen are marked. An increase in vascularity and great hypertrophy of the accessory structures result from its injection into ovariectomized females. (See figs. 51, 52, 53.) Increased irritability and activity of the accessory structures also occur. This increased activity appears to be an important factor in the transportation of sperm upward within the female accessory organs to the region where the egg awaits the sperm’s arrival.

The alterations in behavior of the female as a result of estrogen stimulation may be considerable. Females actually seek the presence of a male during the period of strong estrogenic influence. The long journey of the female fur seal to the mating grounds in the Bering Sea, the bellowing and tireless search of the cow moose, the almost uncontrollable demeanor of seeking the male on the part of the female dog or of the cow in “heat” — these are a few illustrations of the regnant power of this stimulant upon the female mammal.


The culmination of these changes in behavior, resulting in a receptive attitude toward the male, is reached at about the time when the egg is discharged from the ovary in many mammalian species. In certain other mammals the period of heat may precede the ovulatory phenomena.

5) Effects of Estrogen in Other Vertebrates. In the hen, estrogenic hormone causes enlargement and functional activity of the oviduct. Estrogenic substance, when injected into female chicks from the eighteenth to the fortieth day, causes an enlargement of the oviduct to about 48 times the natural size. Estrogen also has a profound effect upon the activities of the full-grown hen and aids in egg production (Romanoff and Romanoff, ’49; Herrick, ’44). Estrogen has a pronounced effect upon the oviducts of other vertebrate forms.


b. Progesterone - The Hormone of the Corpus Luteum

1) Production of Progesterone. The luteinizing hormone, LH, of the anterior lobe of the pituitary gland is concerned not only with the development of the egg follicle, but also, after ovulation or the discharge of the egg from the egg follicle, the remaining granulosa cells, and also, some of the theca interna cells of the follicle are induced by the LH factor to form the corpus luteum (figs. 30, 49). Corpora lutea also may be induced by estrogens. This, however, appears to be an indirect stimulus aroused through estrogenic stimulation of the pituitary gland to secrete added amounts of the LH factor (Evans and Simpson in Pincus and Thimann, ’50, p. 359).


Fig. 52. Characteristic histological changes in the female reproductive tract under the influence of estrogen and progesterone. (A-C) Vaginal cyclic changes in the rat. In (A) is shown the condition of the vaginal wall in the diestrus (resting) condition; (B) shows changes in vaginal wall structure during estrus. Observe cornification of outer layer of cells; (C) shows vaginal wall tissue immediately following estrus, i.e., during metestrus. The presence of progesterone tends to suppress the action of estrogen. (After Turner: General Endocrinology, Philadelphia, Saunders.) (D, E) Cyclic changes of the Fallopian tube of the human female during the reproductive cycle. In (D) is shown the midinterval of the cycle, i.e,, at a time paralleling estrus in mammals in general; (E) shows the cellular condition of the lining tissue of the Fallopian tube just before menstruation. In (D) the tissue has responded to the presence of estrogen; (E) effect of progesterone is shown. (After Maximow and Bloom: A Textbook of Histology, Philadelphia, Saunders.) (F, G) Cyclic changes in the uterine-wall tissue during the reproductive cycle in the human female. In (F) is shown general character of the uterine wall during the follicular phase, i.e., responses to estrogen; (G) shows the general condition of the uterine wall following ovulation. The uterus is now responding to the presence of progesterone added to the follicular or estrogenic stimulation. (After Maximow and Bloom: A Textbook of Histology, Philadelphia, Saunders.)


A further pituitary principle, however, seems to be involved in the functional behavior of the corpus luteum. This principle, referred to as luteotrophin (LTH), is associated with the lactogenic-hormone complex produced by the anterior lobe of the pituitary body; it induces the morphologically developed corpus luteum to secrete progesterone. (Consult Evans and Simpson in Pincus and Thimann, ’50, pp. 359, 360; Turner, ’48, p. 379, for references.)

The structural formula of progesterone is as follows:

2) Effects of Progesterone. Progesterone reduces the irritability of the accessory structures and stimulates the mucosa of the uterus to undergo further development. This increased developmental and functional condition of the


Fig. 53. Relationship of the pituitary gonadotrophins and ovarian hormones to the developing Graafian follicle and reproductive-duct change in a polyestrous female mammal.

The Graafian follicle responds to the pituitary gonadotrophins, FSH and LH, with the subsequent growth and ultimate rupture of the follicle and ovulation. Ovulation terminates the follicular phase of the cycle. Under the influence of the LH factor the corpus luteum is established. The latter becomes functional as a result of stimulation by the luteotrophic (lactogenic) hormone. The progestational hormone (progesterone) then is elaborated by the luteal cells. The activity of the latter together with estrogen controls the luteal phase of the cycle.

The rising level of estrogen in the blood suppresses FSH secretion, and together possibly with small amounts of progesterone stimulates LH secretion. Estrogen and small amounts of progesterone also probably stimulate the secretion of large quantities of LTH, and the latter stimulates the secretion of progesterone from the recently formed corpus luteum. When the estrogen level falls, FSH again is secreted.

When the estrogen level rises, the endometrium of the uterus and vaginal mucosa are stimulated. The presence of progesterone suppresses vaginal development, but the uterine mucosa is stimulated to greater activity. Observe that the involution of the endometrial lining in most mammals is gradual but in primates it is precipitous and violent, resulting in menstruation (Cf. fig. 59). (The diestrous period on this chart is shown as a relatively brief period compared to the other aspects of the reproductive cycle. However, it may be very long in females which do not experience a polyestrous condition and in some species it may last a good portion of a year.) (Compiled from various sources in the literature. The portion of the chart showing pituitary and gonadal hormonal relationships is based on data obtained from The Schering Corporation, Bloomfield, N. J.)


accessory reproductive structures added normally to the estrogenic effects during the reproductive cycle constitutes the luteal phase of the cycle. In this phase of the cycle the uterine glands elongate and begin secretion, and the uterus as a whole is prepared for gestation as a result of the action of the progestational hormone, progesterone, associated with estrogen. (See figs. 53, 59.)

F. Reproductive State and Its Relation to the Reproductive Cycle in Female Vertebrates

The changes in the female reproductive organs resulting in structural growth and development referred to above (70-74, 85-88) are consummated in the ability of the female to fulfill the reproductive functions. The phase of the reproductive events characterized by the ability to reproduce is known as the reproductive climax. This period of culmination remains for a brief period, to be followed by recession and involution once again to a resting condition. This developmental progression to a state of reproductive climax followed by regression to a resting condition constitutes a cycle of changing events. When conditions again are right, the cycle is repeated. Each of these cyclic periods is known as a reproductive or sexual cycle (figs. 53-59). The reproductive life of all female vertebrates is characterized by this series of cyclic changes.

In most vertebrate species, the female experiences one sexual cycle per year, which corresponds to the seasonal cycle in the male. However, in various mammals and in certain birds, such as the domestic hen, several or many reproductive cycles may occur during the year. The male, under these conditions, is a continuous breeder; that is, he produces sperm continuously throughout the year.

1. Sexual Cycle in the Female Mammal a. Characteristics and Phases of the Reproductive Cycle

The estrous cycle in mammals is a complex affair composed of a number of integrated subcycles. The changes occurring in the ovary are called the ovarian cycle; the cellular changes in the uterine (Fallopian tube) form a cycle; the responses in the mammary glands constitute the mammary cycle; the cyclic events in the uterus make up the uterine cycle, while those in the vagina form the vaginal cycle (figs. 53, 54, 57).

The entire estrous cycle may be divided by ovarian changes into two main phases: the follicular phase and the luteal phase (fig. 53). The former is under the immediate influence of the enlarging Graafian follicle, which in turn is stimulated by the follicle-stimulating and luteinizing hormones of the pituitary gland, with the subsequent production of estrogen. It is probable that the luteinizing hormone, LH, is mainly responsible for estrogen secretion. (See Evans and Simpson in Pincus and Thimann, ’50, p. 355.) The luteal phase on the other hand is controlled by the activities of the corpus luteum, which has replaced the Graafian follicle under the influence of the luteinizing hormone. The production of progesterone by the corpus luteum is effected as stated previously by the pituitary hormone, luteotrophin (LTH). Ovulation is the pivotal point interposed between these two phases. The follicular phase may occur without ovulation, but the true luteal phase of a normal or fertile reproductive cycle is dependent upon the ovulatory phenomena. Certain luteal conditions may be elaborated in an anovulatory cycle, but we are here concerned with the normal events of the fertile reproductive cycle.

The follicular phase includes that portion of the reproductive cycle known as proestrus and a considerable part of estrus. Proestrus is the period of rapid follicular growth and elaboration of the estrogenic substance which precedes the period of estrus. Estrogen stimulates developmental changes in the cellular structure of the accessory reproductive organs, particularly the vagina and the uterus (figs. 52, 53). Estrus represents the climax of the follicular phase. As such, it is a period of sexual receptivity of the male, and, in spontaneously ovulating forms, of ovulation. During other periods of the cycle the female is indifferent or even antagonistic to the male. The period of estrus is often called period of heat, or period of rut. Estrus is followed by pregnancy if mating is allowed and is successful, or, in many species, by a period of pscudopregnancy if mating is not permitted or if the mating is sterile (figs. 53-57). In some animals, such as the dog, pseudopregnancy is a prolonged normal event even if mating does not occur, continuing over a period almost as long as that of normal pregnancy (fig. 54). In other animals, such as the opossum, pseudopregnancy forms but a brief episode.

Pseudopregnancy is, generally speaking, intermediate in duration between that of a normal luteal phase of the cycle and that of gestation. In those female mammals where it does not occur normally, it is aroused by such procedures as sucking of the nipples, stimulation of the vagina and cervix by the natural mating process, or by artificially stimulating these structures. In some forms, such as the rabbit, pseudopregnancy is aroused by mere handling or even by sight of a male. (For discussion, see Selye, ’48, p. 813.)

The general changes of growth and development of the accessory organs which occur during pregnancy and pseudopregnancy are controlled largely by the secretions of the corpus luteum. The conditions thus imposed by the corpus luteum comprise the luteal or progestational phai^e of the cycle (fig. 57).

In most mammals, if pregnancy does not occur, the ovary and accessory organs again gradually return to the sexually-resting condition known as diestrus (fig. 53). In man and other primates the changes within the uterus are not gradual but are precipitous, and most of the endometrial lining, together with considerable amounts of blood, is discharged to the outside (figs. 53, 59). This phenomenon is called menstruation. The causes of menstruation are largely problematical; it is related to the fall of the level of either or both of the ovarian hormones, progesterone and estrogen. Why certain mammals should experience violent endometrial changes evident in menstruation and others a gradual involution and resorption is a question for the future. The general period of change following estrus in a non-fertile cycle is known as metestrus (fig. 53). In the rat and mouse, metestrus is short, about one or two days; in the human and opossum it occupies approximately ten days to two weeks of the cycle; in the dog, about 40 to 50 days, depending upon the pseudopregnant conditions experienced in different females. The word anestrus is applied to a prolonged diestrus or sexual quiescence between two sexual cycles. However, the involution experienced by the sexual organs in anestrus is somewhat more profound than that prevailing during a brief diestrus. The term lactational diestrus is used to refer to the prolonged diestrous condition in forms such as the rat, wherein estrus is suppressed in the mother while suckling the young.

The length of the sexual cycle varies with the species. When females of the rat or mouse are kept away from a male, the estrous or sexual cycle will repeat itself every 4 to 5 days. In the sow it occurs every 17 to 20 days. In the opossum there is a prolonged anestrous period during the summer and autumn months followed by a polyestrous period during the winter and spring when the estrous cycle reoccurs about every 28 days. In the human female, the sexual cycle occupies about 28 days, and there arc probably about ten normal ovulatory cycles in a year. Some human females may have more, while others experience a slightly smaller number of true ovulatory cycles per year.

Many mammals have one estrous cycle per year. This condition, known as monestrus, is true of most wild mammals, such as the deer, wolf, fox, moose, and coyote. In the shrew, mink, and ferret the moncstrous period may be prolonged if the female is kept away from the male.

Various types of polyestrous conditions exist. In the female dog, for example, there are two or three estrous periods per year about 4 to 6 months apart. In the cat there are several cycles about two weeks apart during the autumn, winter, and spring. In the domestic sheep there is a polyestrous period from September to February in which the cycles occur about every 17 days, followed by an anestrous period from early March to September. In the mare in North America, estrous cycles of about 19 to 23 days occur from March to August. In South America the breeding season is reversed, corresponding to the reversed seasonal conditions south of the equator. In England many mares breed in autumn and winter (Asdell, ’46).

In some mammals estrus may follow immediately after parturition or birth of the young. This may occur occasionally in the rat. Under normal conditions in the fur seal, the female lactates and gestates simultaneously. It is not a common procedure.

It should be observed that there are two aspects of the female reproductive cycle of the mammal relative to fertilization or the bringing together of the male and female reproductive cell. One aspect is the sexual receptivity of the female; the other is the time of ovulation of the egg. In most female mammals sexual receptivity and ovulation are intimately associated and occur spontaneously in the cycle; in others the two events may be separated. In the former group, the development of “heat” and the maturing of the egg follicle are closely associated, while in the latter the conditions favoring sexual receptivity or heat are developed considerably in advance of the maturation of the follicle, as noted in the table below.

b. Relation of Estrus and Ovulation in Some Common Mammals


1) Spontaneously Ovulating Forms (Sexual Receptivity of Male Occurs at or near Time of Ovulation):


Length of Estrus or Period of Heat

Time of Ovulation

Dog

True period of heat about 5-10 days in the middle of a 21 -day estrous period

Variable: 1st day; 2nd day; 5th day; etc., of true period of heat

Guinea pig

6-1 1 hrs.

Views vary: 1-2 hrs. after heat or estrus begins; 10 hrs. after; at end of estrus

Man

Receptivity not always related to cyclic events

12-17 days after onset of preceding menstruation; average around 14th day

Mare

2-11 days; average length 5-6 days

About 1-2 days before end of estrus; best breeding about 3 days after heat begins

Sheep

About 36 hrs.

Late in estrus or just after estrus


ends; presumably about 20-36 hrs. after estrus begins


Sow

Silver fox

Rat

15 days

1-5 days; occurs once a year in February

One determination estimates estrus to be 9-20 hrs.; most receptive to male about first

3 hrs. of heat. Another determination estimates estrus to be 12-18 hrs.

About 1-3 days after onset of estrus 1st or 2nd day of estrus

8 -11 hrs. after beginning of heat

2) Dependent Ovulatory Forms (Sexual Receptivity (Heatl Occurs Previous to Time of Ovulation);


Length of Estrus or Period of Heat

Time of Ovulation

Cat

2-3 days

Time of ovulation uncertain but is


dependent upon copulation



Length of Estrus or Period of Heat

Time of Ovulation

Rabbit (tame)

Estrus prolonged indefinitely during the breeding season from spring to summer; a series of different sets of egg follicles matured; each series lasts about a week, then becomes atretic

Ovulation 10-14 hrs. after mating

Shrew

Estrus prolonged

About 55 -70 hrs. after mating

Ferret

Estrus prolonged

About 30 hrs. after mating


If ovulation and subsequent pregnancy are not permitted by mating, ovarian involution occurs, and an anestrous interlude is established. Anestrus in the common rabbit, Oryctolagus cuniculus, occurs from October to March, but is not absolute.


c. Non-ovulatory (Anovulatory) Sexual Cycles

Not all of the cyclic changes referred to above in those species which normally experience spontaneous ovulation are related to definite egg discharge. Some cycles occur, more or less abortively, without ovulation of the egg. This may happen in the human or in other mammals, such as the dog and monkey. Cycles without ovulations are called non-ovulatory cycles. Menstruation may follow non-ovulatory cycles in the human female.

d. Control of the Estrous Cycle in the Female Mammal

In the control of a reproductive cycle in the vertebrate animal, three main categories of factors appear to influence its appearance and course. These are:

(1) external environmental factors, such as light and temperature,

(2) external factors governing food supply, and

(3) internal factors resulting from an interplay of the activities of the pituitary gland, the ovary, general body health, and of the particular hereditary constitution of the animal.

These factors should be considered not alone in terms of the immediate production of fertile conditions in the parent, but rather, in view of the total end to be achieved, namely, the production of a new individual of the species. For example, the reproductive cycle in the deer reaches its climax or estrus in the autumn after a long period of lush feeding for the mother. The young are born the next spring amid favorable temperatures, followed by another period of bountiful food supply for the mother during lactation and for the fawn as it is weaned. A receding light factor in the late summer and early fall thus may be correlated with the period of heat, which in turn proves to be an optimum time of the year for conception with the resulting birth the following spring. Similarly, light ascendency is a factor in producing fertility in many birds. Here the incubation period for the young is short and a plentiful supply of food awaits the parents and young when it is needed. In other words, the factors which induce the onset of the reproductive state are correlated with the conditions which enhance the end to be achieved, namely, the production of a new individual.

Let us consider next the internal factors which induce the breeding state in the female mammal. The commonly held theory regarding the pituitaryovarian relationship governing the control of the reproductive periods in the mammal which ovulates spontaneously is as follows (figs. 53 and 59) :

( 1 ) FSH of the pituitary gland stimulates later follicular growth. This factor probably is aided by small amounts of the luteinizing factor, LH, to effect an increased production by the ovarian tissues of the estrogenic hormone. Early follicle growth probably occurs without FSH.

(2) Estrogen output by the ovary rises steadily during the period previous to ovulation.

(3) Old corpora lutea or other ovarian tissue possibly secrete minimal amounts of progesterone under the influence of lutcotrophin, LTH.

(4) As the quantity of estrogen rises in the blood stream, it inhibits the production of FSH and together with small quantities of progesterone, increases the output of LH from the pituitary gland. This combination also may cause an increased outflow of the luteotrophic factor.

(5) An increased amount of LH aids in effecting ovulation and the subsequent luteinization of the follicle. As the follicle becomes converted into the corpus luteum, the presence of the luteotrophic factor brings about the formation of increased quantities of progesterone and maintains for a time the corpus luteum and the functional luteal phase of the cycle.

(6) In those mammals possessing a scries of repeating sexual cycles, it is assumed that the fall of estrogen in the blood stream after ovulation suppresses the LH outflow and permits a fresh liberation of FSH from the anterior lobe of the pituitary gland, thus starting a new cycle. The lowering of the estrogen level may be particularly and immediately effective in forms such as the rat and mouse, which have a short metestrus or luteal phase in the estrous cycle.

e. Reproductive Cycle in Lower Vertebrate Females

While the words estrus, heat, or rut are generally applied to the mammalian groups, the recurrent periods of sexual excitement in lower vertebrates are fundamentally the same sort of reaction, although the changes in the reproductive tract associated with ovarian events are not always the same as in mammals. However, similar cyclic changes in the ovary and reproductive tract are present in the lower vertebrates, and their correlation with the activities of the pituitary gland is an established fact. Consequently, the words estrus, rut, sex excitement, and heat basically designate the same thing throughout the vertebrate series — namely, a period during which the physiology and metabolism of the parental body is prepared to undertake the reproductive functions. In this sense, the words estrus, anestrus, heat, etc. also may be applied to the male as well as to the female when the male experiences periodic expressions of the sexual state.

Although the reproductive cycle in all vertebrates represents basically a periodic development of the reproductive functions, there is a marked difference between the estrous cycle in the female mammal and the reproductive cycle in most of the other female vertebrates with the exception of viviparous forms among the snakes, lizards, and certain fishes. This difference is due to the absence of a true luteal phase in the cycle. The follicular phase and elaboration of estrogen appears to be much the same in birds, amphibia, and fishes as in the mammals, but the phase of the cycle governed by progesterone secretion, associated with a gestational condition in the accessory reproductive organs, is found only among those vertebrates which give birth to their young alive.

The reproductive cycles in certain vertebrates may be changed by selective breeding and domestication. For example, the domestic hen is derived from the wild jungle fowl. The jungle fowl conform to the general stimuli of nature as do most wild birds, and the reproductive cycle is associated with a particular season of the year. However, domestication and selection by man of certain laying strains have altered the original hereditary pattern of seasonal laying. Consequently, good layers will lay eggs over an extended period of the year, although there is a strong tendency to follow the ancestral plan by laying most of the eggs during the spring and summer months; during the fall and winter months, a smaller number of eggs are laid. Some of the varieties of the domestic hen conform more closely to the ancestral condition than do other strains. Similar changes may be produced in the buffalo, which in nature breeds in middle to late summer but in captivity has estrous periods three weeks apart throughout the year (Asdell, ’46).

G. Role of the Ovary in Gestation (Pregnancy)

1. Control of Implantation and the Maintenance of Pregnancy in Mammals

The ruling power of the ovary over the processes involved in pregnancy is absolute, particularly during its earlier phases. In the first place, the corpusluteum hormone, progesterone, is necessary to change the uterus already conditioned by the estrogenic hormone into a functionally active state. The latter condition is necessary for the nutrition and care of the embryo. A second change which the gestational hormone imposes upon the genital tract of the female is to quiet the active, irritable condition aroused by the estrogenic factor. Progesterone thus serves to neutralize or antagonize the effects of the estrogenic hormone. A placid condition of the uterus must be maintained during the period immediately following copulation if the fertilized egg is to be cared for within the uterine structure. Large doses of estrogens injected into mammals shortly after copulation prevent implantation of the embryo in all species thus far studied. (See Selye, ’48, p. 822.)

A third effect of the presence of progesterone is the inhibition of the copulatory responses. Immediately following estrus and ovulation, the female dog will fight off the aggressiveness of the male — an aggressiveness which she invited a day or two previously. This change in behavior is introduced by the development of the corpora lutea and the initiation of the luteal phase of the reproductive cycle. Similar anaphrodisiac changes are sometimes mentioned in the behavior of the human female during the luteal phase of the cycle. Progesterone injections also inhibit the copulatory responses in the ferret (Marshall and Hammond, ’44). All of the above-mentioned activities of progesterone thus inhibit or antagonize the condition aroused by estrogenic stimulation.

However, aside from these immediate metestrous and post-ovulatory changes in behavior induced by progesterone, one of its most essential aetivities is concerned with the maintenance of gestation or pregnancy. Ovariectomy or the removal of the ovaries at any time during the gestational period in the rat, mouse, and goat results in death and abortion of the embryo. During the first part of pregnancy in the rabbit, the ovaries must be left intact but may be removed in the closing phase without endangering the gestational process. In the human female, and also in the mare, cat, dog, guinea pig, and monkey, the ovaries may be removed during the latter half of pregnancy without danger to the offspring. However, ovariectomy performed in the early stages of pregnancy in these animals, as well as in all other mammals thus far studied, produces abortion (Pincus, ’36; Selye, ’48, p. 820). The corpus luteum hormone, therefore, is essential in the early phases of gestation in all mammals, and it appears to be necessary during most of the pregnant period in many other mammals.

It is highly probable that the placenta takes over the elaboration of progesterone in those mammals where ovariectomy is possible after the first part of pregnancy has elapsed. In the human female the corpus luteum normally involutes at about the third month of pregnancy, but progesterone may be extracted from the placenta after this period.

Although certain effects of the estrogenic hormone appear to be neutralized (or antagonized) by progesterone during the early phases of reproduction, other effects of estrogen in relation to progesterone are important for the maintenance of the pregnant condition. In this connection the estrogenic hormone appears to suppress some of the growth-promoting effects of progesterone. The two hormones thus work together to promote a gradual development of the uterine tissue and maintain a regulated, balanced condition throughout pregnancy. The placenta, through its ability to elaborate progesterone and estrogen during the latter phases of pregnancy, is an important feature regulating pregnancy in some mammals.

It should be emphasized in connection with the above statements that the presence of the fertilized egg and its subsequent development in some manner affects the maintenance of the corpus luteum. The mechanism by which this influence is conveyed to the ovary is unknown.

2. Gestation Periods, in Days, of Some Common Mammals*

  • Adapted from Asdell, ’46; Cahalane, ’47; Kenneth, ’43.


Armadillo (Dasypus novemcinctus)

150

Bear, black (Ursiis americanus)

210

Bear, polar (Thalarctos maritimus)

240

Beaver, Canadian (Castor canadensis)

94-100

Bison (Bison bison)

276

Cat, domestic (Felis catus)

60

Cattle (Bos taurus)

282

Chimpanzee (Pan satyrus)

250

Deer, Virginian (Odocoileus virginianus)

160-200

Dog, domestic (Canis familiaris)

58-65

Donkey, domestic (Eqiius asinus)

365-380

Elephant (Elephas africanus)

641

Elephant (Elephas indicus)

607-641

Elk (A Ices alces)

250

Ferret (Putorius faro)

42

Fox, arctic (Alopex lagopus)

60

Fox, red (Vulpes vulpes and V. fulva)

52-63

Giraffe (Giraffa Camelopardalis)

450

Goat, domestic (Capra hircus)

140-160

Guinea pig (Cavia porcellus)

68-71

Horse (Equus cabaltus)

330-380

Man (Homo sapiens)

270-295

Lion (Felis leo)

106

Lynx (Lynx canadensis)

63

Marten, American (Martes americana)

267-280

Mink (Mustela vison)

42-76

Mole (Talpa europaea)

30

Monkey, macaque (Macaca mulato)

160-179

Mouse, house (Mas rnusculus)

20-21

Opossum (Didelphis virginiana)

13

Pig (Sus scrofa)

115-120

Rabbit (Lepus; Sylvilagus; Oryctolagus)

30-43

Rats (Various species)

21-25

Seal, fur (Callorhinus sp.)

340-350

Sheep, domestic (Ovis aries)

144-160

Skunk, common (Mephitis mephitis)

63

Squirrel, red (Tamiasciurus sp.) 30-40

Tiger (Felis tigris) 106

Whale (Various species) 334-365

Wolf (Canis lupus) 63

Woodchuck (Marmota monax) 35-42

Zebra, mountain (Equus zebra) 300-345


3. Maintenance of Pregnancy in Reptiles and Other Vertebrates

In certain viviparous species of the genera Storeria, Matrix and Thamnophis, Clausen (’40) reports that ovariectomy during gestation results in resorption of the embryo when performed during the earlier phases of gestation and abortion during the middle of gestation, but during the terminal portion of pregnancy the process is unaffected and the young are born normally. These results are similar to those obtained from the rabbit as noted previously.

While experimental evidence is lacking in other vertebrate groups which give birth to the young alive, the evidence obtained from reptilian and mammalian studies suggests that hormones are responsible for the maintenance of pregnancy. In harmony with this statement, it may be pointed out that in the viviparous elasmobranch fishes (e.g., sharks) corpora lutea are developed in the ovaries.

H. Role of the Ovary in Parturition or Birth of the Young

The real factors bringing about parturition are not known, and any explanation of the matter largely is theoretical. However, certain aspects of the subject have been explored. For example, it was observed above that progesterone appears to antagonize the action of estrogen with the result that the uterus stimulated to irritability and contractility under the influence of estrogen is made placid by the action of progesterone. In harmony with this action studies have shown that estrogen tends to increase during the final stages of normal gestation, while progesterone appears to decrease, accompanied by an involution of the corpora lutea. Consequently, the foregoing facts have suggested the “estrogen theory,” which postulates that activities of the uterine musculature are increased by the added amounts of estrogen in the presence of decreasing amounts of progesterone during the latter phases of pregnancy. In confirmation of this theory, it has been shown that progesterone injected into a pregnant rabbit near the end of the gestation period will tend to prolong gestation. A second theory of parturitional behavior assumes that the posterior lobe of the pituitary gland elaborates oxytocin which induces increased uterine activity, resulting in birth contractions (Waring and Landgrebe in Pincus and Thimann, ’50). Again, a third concept emphasizes Ihe possibility that the placenta may produce substances which bring about contractions necessary for the expulsion of the young (Turner, ’48, p. 428). Oxytocic substances have been extracted from the placenta, which suggests the validity of this theory.


Fig. 54. Changes occurring in the reproductive organs and mammary glands of the bitch during the reproductive cycle. The student is referred to Asdell (’46), pp. 150-156 and Dukes (’43), pp. 678-682, for detailed description and references pertaining to the data supporting this chart. The gestation period is based upon data supplied by Kenneth (’43) and the author’s personal experience with dogs.


Fig. 55. Reproductive and pregnancy cycles in the sow. (Modified from data supplied by Corner, Carnegie Inst., Washington, pub. 276, Contrib. to Embryol., 13; the parturition data derived from Kenneth, ’43.)


The specific functions of the ovary in parturition probably are more pronounced in those forms where it is essential throughout most of the gestational period, such as the viviparous snakes, and among the mammals, such forms as the opossum, rat, mouse, and rabbit. The waning of corpus-luteum activity in these species may serve to lower the level of progesterone in the body and thus permit some of the other factors, such as estrogen or the pituitary principle, to activate the uterus.

Another factor associated with the ovary and parturition is the hormone relaxin. This substance was first reported by Hisaw and further studied by this investigator and his associates (Hisaw, ’25, ’29; and Hisaw, et al., ’44).


Fig. 56. Reproductive and pregnancy cycles in the mare. (Parturition period based upon data supplied by Kenneth (’43); other data supplied by Asdell (’46) and Dukes (’43).) It is to be noted that the first corpus luteum of pregnancy degenerates after about 35 days; the second “crop of corpora lutea” (Asdell) degenerate by 150 days. The ovaries may be removed after 200 days of pregnancy without causing abortion of young.

Relaxin aids in the production of a relaxed condition of the pelvic girdle, a necessity for the formation of a normal birth passageway for the young. Relaxin somehow is associated in its formation with the presence of progesterone in the blood stream and also with the intact reproductive system. Relaxin together with estrogen and progesterone establishes a relaxed condition of the tissues in the pubic area of the pelvic girdle.

I. Importance of the Ovary in Mammary-Gland Development and Lactation

Estrogen and progesterone together with the lactogenic hormone, luteotrophin, of the pituitary gland are necessary in mammary-gland development. The entire story of the relationship of these and of other factors in all mammals or in any particular mammal is not known. However, according to one theory of mammary-gland development and function, the suggestive roles played by these hormones presumably are as follows (fig. 58): Estradiol and other estrogens bring about the development of the mammary-gland ducts; as a result a tree-like branching of the ducts is effected from a simple im


Fig. 57. Reproductive and pregnancy cycles in the cow. (Parturition period based upon data supplied by Kenneth (’43), also by Asdell (’46), Other data for chart derived from Asdell (’46).

Three main characteristics of heat or estrous period are evident: (1) A duration of heat of only about 10 to 18 hours; (2) abundant secretion during heat of a “stringy mucus,’’ derived from mucoid epithelium of vagina and from sealing plug of cervix when cow not in estrus (Asdell); and (3) ovulation occurs from 13Vi to 15Vi hours after termination of estrus (Asdell), Variation in time of ovulation may be considerable, from 2 hours before end of estrus to 26 hours after (Asdell).

mature pattern established during earlier development (fig. 5 8 A, A', B). The male mammary gland may remain similar to the condition shown in fig. 58A. The maturing of the egg follicles within the ovary and the concomitant formation of estrogen which accompanies sexual maturity is linked with the more complex state of the mammary-gland system shown in fig. 58B.

The next step of mammary-gland development is carried out under the influence of progesterone. Progesterone is necessary for the development of the terminal glandular tissue or alveoli associated with these ducts (fig. 58C, D). Finally, the pituitary lactogenic hormone (luteotrophin [LTH]; prolactin) stimulates the actual secretion of milk (fig. 58E). Recent research also has shown that the lactogenic hormone collaborates in some way with estrogen and progesterone in the development of the mammary-gland tissue.



Fig. 58. Mammary gland changes in relation to reproduction. (Figures are a modification of a figure by Corner: Hormones in Human Reproduction, Princeton, Princeton University Press. The figure in the latter work was based on a figure by C. D. Turner: Chap. XI of Sex and Internal Secretions, by Allen, et al., Baltimore, Williams & Wilkins, 1939.) Factors involved in mammary gland development and secretion are somewhat as follows: (A, A') Condition of the young, infantile gland. (B) Development from a simple, branched, tubular gland of the immature animal (A') into a compound tubular gland presumably under the direct stimulation of estrogen, according to one theory, or by the action of estrogen upon the pituitary gland which then releases mammogen I, producing these changes, according to Turner, et al.: Chap. XI, Sex and Internal Secretions, by Allen, et al., Baltimore, Williams & Wilkins. (C) Transformation of the compound tubular gland into a compound tubulo-alveolar gland under the influence of progesterone, during the first part of pregnancy, or, according to Turner, et al., by the influence of estrogen plus progesterone which causes the pituitary to release a second mammogen which produces the alveolar transformation. (D) Effect of the latter part of pregnancy is to bring about a development of the cells of the acini of the acinous or alveolar system. The unit shown in (D) represents a simple, branched, acinous gland, in which there are six alveoli or acini associated with the duct. (E) Affect of parturition is to release the lactogenic hormone (prolactin; luteotrophin) from the pituitary gland which brings about milk secretion. During pregnancy the high levels of estrogen presumably inhibit milk secretion. However, following pregnancy the level of estrogen is lowered permitting lactogenic-hormone action upon the alveoli of the gland.

The removal of the placenta and embryo at any time during gestation permits milk flow, provided the mammary glands are sufficiently developed. In the human, any remains of the placenta after birth inhibit milk secretion, probably because the estrogenic hormone is elaborated by the placental remnants. (See Selye, ’48, p. 829.)

In the rabbit, estrogen and progesterone are necessary for the elaboration of the duct and secretory acini; in the guinea pig and goat, and to some extent in the primates, including the human female, estrogen alone is capable of producing the development of the entire duct and acinous system. (See Turner, ’48, p. 430.)


During pregnancy, the actual secretion of milk is inhibited by the estrogenic hormone produced by the ovary and the placenta. The role of estrogen as an inhibitor of lactation is suggested by the fact that, after lactation has started following normal parturition, it is possible in the cow and human to suppress milk flow by the administration of estrogens. After parturition, however, estrogen is no longer present in^sufflcient amounts to suppress the secretion of milk, and the mammary gland begins to function. (In the fur seal a postpartum estrus with ovulation follows a short time after parturition. However, the amount of estrogen produced by this reproductive cycle is not sufficient to curb lactation.) The neurohumoral reflex, or “suckling reflex,” produced by the sucking young appears to maintain the flow of milk over a period of time. Probably this reflex causes a continuous discharge of the lactogenic hormone from the anterior lobe of the hypophysis.

Another theory of mammary-gland development maintains that estrogen stimulates the anterior pituitary gland to release mammogen, which causes development of the duct system, and estrogen plus progesterone induce a second mammogen which stimulates lobule-alveolar development. The lactogenic hormone produces the actual secretion of milk. The ovary thus assumes considerable importance in controlling the (morphological) development of the mammary glands in mammals, particularly in those forms in which the functional condition of the ovary is maintained throughout most of the gestational period, e.g., rat, rabbit, dog, etc. In other species, such as the human, mare, etc., the placenta through its ability to duplicate the production of the ovarian hormones, assumes a role during the latter phase of pregnancy. (For further details, consult Folley and Malpress in Pincus and Thimann, ’48; Selye, ’48, pp. 828-832; and Turner, ’48, pp. 428-448.)


Fig. 59. Stages in the reproductive cycle of the human female and its pituitary-ovarianendometrial relationships (Cf. fig. 53). (Compiled from various sources in the literature.) (a) As shown at the extreme right of the figure, a fall in the level of estrogen and progesterone in the blood stream, either or both, is associated with endometrial necrosis, bleeding, and discharge (menstruation), (b) The lowering of the estrogen level is associated with a new outflow of the follicle-stimulating hormone (FSH), as shown at the right of the figure, (c) In the left side of the figure, the influence of FSH induces egg follicles, probably several, to grow. Antral spaces appear and enlarge. The presence of a small amount of the luteinizing hormone (LH) together with FSH stimulates the secretion of estrogen by the ovarian tissues, possibly by the follicles and interstitial tissue between the follicles, (d) In consequence, the estrogen level rises in the blood stream, and menstruation subsides by the fourth day. (e) The continued influence of estrogen produces endometrial growth, and probably increases the outflow of LH from the pituitary (fig. 53). It is probable, also, that the increased estrogen level stimulates a release of the luteotrophic hormone from the pituitary, which in turn stimulates the formation of a small quantity of progesterone by either the interstitial tissue of the ovary or in old corpora lutea. (f) Some of the developing egg follicles degenerate, while one continues to develop, (g) The elevation of estrogen suppresses the outflow of FSH as indicated by the heavy broken line to the left, (h) The elevated level of estrogen together possibly with small amounts of progesterone evokes an increased outflow of LH and LTH as indicated by the heavy broken line to the right, (i) LH and FSH bring about ovulation at about the fourteenth day. (j) LH causes development of corpus luteum. (k) LTH elicits secretion of progesterone by corpus luteum. Possibly some estrogen is secreted also by corpus luteum. (1) Progesterone and estrogen stimulate added development of endometrium, (m) In the absence of fertilization of the egg, the corpus luteum regresses, with a subsequent fall of progesterone and estrogen levels in the blood stream, terminating the cycle and permitting a new menstrual procedure.


In the dog or opossum during each reproductive cycle, the mammary glands are stimulated to grow and may even secrete milk (dog). These changes closely parallel the ovarian activities, particularly the luteal phase of the cycle. In the human, functional growth changes occur in pregnancy, but, pending the events of the ordinary cycle, alterations in the duct system are slight although the breasts may be turgid due to increased blood flow and connectivetissue development.

J. Other Possible Developmental Functions Produced by the Ovary

As the eggs of the opossum and rabbit travel through the uterine (Fallopian) tube toward the uterus, they are coated with an albuminous, jelly-like coating. Similar jelly coatings are added to the eggs of the bird, reptile, frog, toad, and salamander. These coatings or membranes added to the egg as it travels through the oviduct are known as tertiary egg membranes.

In the toad, the secretion of the protective jelly by the oviduct can be elicited by the lactogenic hormone present in beef pituitary glands. The secretion of the albuminous jelly coatings around the eggs of frogs, salamanders, reptiles, and birds may be related to this hormone. The formation of the crop milk of pigeons has been shown by Riddle and Bates (’39) to be dependent upon the presence of the lactogenic hormone.

The function of the ovary in influencing the outflow of the lactogenic hormone from the pituitary, if present in the above cases of glandular secretion, must be an indirect one. Evans and Simpson in Pincus and Thimann (’50) ascribe the outflow of the “lactogenic hormone (luteotrophic hormone)” of the mammalian pituitary to estrin produced by the ovary. It is possible that in the salamanders, frogs, toads, and the birds an indirect ovarian influence may similarly induce secretion of the lactogenic hormone which in turn governs the elaboration of the albuminous jelly deposited around the egg in transit through the oviduct.

K. Determinative Tests for Pregnancy

Various tests have been used to determine the probability of pregnancy in the human female. These tests are discussed in Chapter 22.


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Cite this page: Hill, M.A. (2024, June 25) Embryology Book - Comparative Embryology of the Vertebrates 1-2. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Book_-_Comparative_Embryology_of_the_Vertebrates_1-2

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