Book - The Hormones in Human Reproduction (1942) 2

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Corner GW. The Hormones in Human Reproduction. (1942) Princeton University Press.

   Hormones in Human Reproduction (1942): 1 Higher Animals | 2 Human Egg and Organs | 3 Ovary as Timepiece | 4 Hormone of Preparation and Maturity | 5 Hormone for Gestation | 6 Menstrual Cycle | 7 Endocrine Arithmetic | 8 Hormones in Pregnancy | 9 Male Hormone | Appendices
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Chapter II The Human Egg and the Organs that Make and Care For It

"All those parts of the Hen which are designed to Generation, namely the Ovary, Infundibulum, the process of the Womb, and the Womb itself, and the Privities: and also the scituation, fabrick, quantity, and Temper of all these, and whatsoever else relates thereto: they are all inservient, and handmaids either to the procreation of the Egge, or to its Augmentation, or else to Coition, and fertility received from the Male, or to the foetus: to which they conduce either necessarily or principally, or as a Causa sine qua non, or some other way to the better being. For there is nothing made either vain or rash in all the operations of Nature." - William Harvey, Anatomical Exercitations Concerning the Generation of Living Creatures, 1653.

What can we say of the ovary, an organ so remarkable that it is able to produce the Egg? The human ovaries (Plate V, ovary) are insignificant-looking whitish, tough bits of animal tissue each about the size of a small walnut[1] hanging from the broad ligament at the back of the pelvic cavity, beside the uterus. They were frankly a puzzle to the ancient anatomists, who never imagined that mammals have eggs and could not have seen the tiny human eggs in the ovary anyway. The hen's egg and ovary they understood much better, for they could see in the ovary the developing yolks of various sizes and thus they perceived the connection between the organ and the ova it produced.

In another place[2] I have told the story of the discovery of the mammalian ovum - how in 1672 the brilliant young Dutchman Regner de Graaf described what we now call Graafian follicles or simply ovarian follicles, round egg chambers, filled with fluid, that he saw in the ovaries of cows, sheep, swine, rabbits, and women (Plate VI, B, C, E). Familiar, of course, with the eggs of birds, he thought each follicle in the mammal was an egg. He was surprised, however, that he could not find such "eggs" after they left the ovary, for in large animals the mature follicles are as big as peas or small cherries, and ought to bulge the oviducts as the hen's eggs do. After long and futile search for the real egg by many workers, Karl Ernst von Baer solved the puzzle in 1827 by finding that the actual egg is a very small speck inside the follicle, too small to be picked out by the unaided eye. If we take one out of its place in the ovary and put it by itself in a dish of clear water in a bright light it can just barely be seen.

With modern instruments we can make a very thin slice of an ovary, put it under the microscope, and photograph it. Studying the slide from the surface down (Plate VII, B) we see a layer of covering cells (germinal epithelium), appearing as a dark line at the top of the photograph, with a vague zone of connective tissue beneath it, a zone of egg cells in reserve (c) and follicles (/) of various sizes, each containing its egg.

The follicle (see again Plate VII, ^) is lined with a layer which looks granular under low magnification, because it is made up of small cells. Just outside this granulosa layer is a thin layer (called thee a interna) of larger cells well supplied with blood vessels. This layer, so slight that it would hardly be noticed, except by an experienced microscopist, is of great importance because in all probability it is the source of the estrogenic hormone which (next to the egg) is the most important product of the ovary.

How the eggs are formed in the ovary is an unsettled problem. We know that large numbers of them are produced by ingrowth from the surface cells of the ovary before birth. In a newborn baby girl there are already thousands of egg cells, many more than she can possibly need when she grows up. Many anatomists think that these original eggs, present at birth, furnish the supply for life ; in other words, that no new ones are formed after birth. This means that the infant in arms has already set aside her contribution to the heredity of her children, and if perchance she has her last baby at forty years of age, that particular egg will have waited all those forty years for its opportunity to develop. This is somewhat staggering, but not altogether preposterous, for we have good reason to think that some other very important cells, e.g. the chief cells of the brain and spinal cord, last a whole lifetime without replacement. Other anatomists think they can see scraps of evidence that new crops of eggs are continually being formed in the ovary of the adult woman, and that these new eggs are those which are shed from the ovary in adult life. It is well known that the male germ cells are formed anew continuously in adult animals (see Chapter IX). The question, as regards the ovary is (for technical reasons) much more difficult to solve than it might seem. I have myself studied it quite seriously in a large collection of monkey ovaries, and thus far have not seen good evidence that new formation of eggs occurs. For this reason I adhere cautiously to the old view until new evidence is brought forward.

Plate V. The human female reproductive organs, drawn by a famous medica illustrator, the late Max Broedel. Above, viewed from dorsal (rear) aspect. Belou viewed from above, as seen by surgeon looking into the pelvis. One-half natura size. From the Carnegie Contributions to Embryology, by courtesy of George B Wislocki.

At any rate, some of the eggs in the reserve zone are from time to time selected to proceed to maturity. Such an egg sinks deeper into the ovary. The cells about it multiply to form a thick mass, which soon hollows out to form a small follicle. As the cavity enlarges, the egg is left in its little hillock at one side (Plate VII, A, B,C).

Discharge of the egg

The follicle continues to grow and to occupy more and more space, slowly shoving aside neighboring tissues within the ovary. Finally it enters a period of very rapid growth, so that its volume doubles in a few hours. Plate VIII shows the growth of the follicle in the rat. The human follicle becomes 12 or 15 millimeters (0.5 to 0.6 inch) in diameter when fully developed and occupies at least onefourth of the whole volume of the ovary. As it enlarges, it pushes its way to the surface. The wall of the follicle next the surface and the overlying capsule of the ovary become thinner and thinner. The actual rupture of the follicle through the thinned-out region has been observed repeatedly in rabbits and sheep, following the lead of Walton and Hammond of Cambridge, England (1928), and has been photographed in motion pictures by Hill, Allen and Kramer of Yale Medical School. It happens that in the rabbit these events in the ovary can be timed very closely. The investigators anesthetize an animal which is about to ovulate and expose one of its ovaries under warm salt solution. Several ripening follicles are seen. Watching or photographing one of these, they see the thin exposed wall of the follicle weaken still more, until it bulges to make a little bleb. Meanwhile the cells about the egg on the inner wall of the follicle have loosened up so that the egg is nearly free from its attachment. Finally the bleb rips open and the contents of the follicle is expelled, carrying the egg with it. In motion pictures, the ejection of the contents looks like the slow rise and fall of a geyser; it is not explosive, but actually rather a gentle occurrence. In animals like the rabbit, which produce several young at one time, the individual follicles of one batch rupture within a few minutes of each other.

Plate VI. De Graafs original illustration of the Graafian follicles, in the ovary of the cow, from De organis generationem inservientibus, 1672. A large follicle is shown at B, smaller ones at C, C, C, C. E is & large follicle dissected away from the ovary. The lower portion of the figure shows the oviduct (Fallopian tube) with its funnel-like expansion. Approximately natural size.

Fig. 8. The human female reproductive system. Dotted lines indicate the position of the pelvis and other bones. From Attaining Womanhood, by George W. Corner, by courtesy of Harper and Brothers.

The egg

The eggs of mammals, seen under the microscope, are beautiful little spherical objects, consisting of a round mass of cellular material surrounded by a transparent zone or membrane (Plate VII, D). The eggs of all the higher mammals thus far measured have been not far from 0.1 millimeter (0.004 inch) in diameter. Mouse and rat eggs are a little smaller (0.075 mm.), those of dog, cow, and human a little larger (0.140 mm.). Dr. Carl G. Hartman suggests a striking comparison by which we can appreciate their size, relative to more familiar objects: "Scatter a pinch of sea sand on a piece of black paper — the smallest grain visible to the naked eye is of the order of magnitude of the cow's egg.

As Hartman calculates, it would require about 2,000,000 eggs to fill an average sewing thimble.

We know fairly well the appearance and size of the human ovum while it is still in the growing follicle of the ovary, but our information about the fully mature egg (that is, during the last hours before it leaves the ovary, and while it is in the oviduct) is derived from a mere handful of specimens, about ten or twelve in all, that various investigators have been able to obtain. The Rhesus monkey has yielded to science a somewhat larger treasure of eggs. If anyone wants monkey eggs in market lots, they might be furnished for two or three thousand dollars a dozen. To compensate for this scarcity of primate eggs, those of the laboratory animals are fairly easy to collect, and the domestic pig is a prime source. I have myself handled 2,500 or more sow's eggs and used to demonstrate them annually to my medical students. Any highschool biology teacher who lives near a slaughterhouse, if he will learn the tricks of finding and handling them, can show his boys and girls this striking evidence of the unity of living things.

The clear outer membrane of the mammalian egg is tough, like a very stiff gelatine solution, stifFer yet than a housewife would serve for dessert. I have often pushed the eggs of rabbits and pigs over the bottom of a dish of salt solution, using a coarse needle which under the microscope looked like a poker pushing a grape. The tough egg membrane easily resists such handling, but if a thin glass microscopic cover slip is allowed to settle down upon an egg in a drop of water, the clear membrane splits open under its pressure like the skin of a grape and pops out its soft contents. It seems to me quite remarkable that the infinitesimal sperm cell can push its wa}' through this barrier.

Plate VII. Structure of the ovary. A, diagram of a section through ovary, illustrating the structures described in the text. From an article by the author, in Physiological Reviews, by permission of the editor. B, pliotograph of small part of a microscopical section of a monkey's ovary. The letter c indicates the cortex of the ovary, containing egg cells not yet surrounded by follicles, o.f., an atretic (degenerating) follicle. Photograph magnified 50 diameters. C, photograph oif section of ripe egg of Rhesus monkey, in its hillock inside a large follicle (Corner collection, no. 100). Magnified 100 diameters. D, photograph of living human egg, recovered from Fallopian tube at operation. Preparation by Warren H. Lewis (Carnegie collection, no. Template:CE6289). Magnified 200 times.

Some eggs, like those of the pig, are heavily laden with fat globules (yolk) ; others, e.g. those of the rabbit, are so clear that the nucleus, inevitable part of a living cell, can be descried in the fresh egg. The human egg, as will be seen from our photograph (Plate VII, D), is moderately filled with yolk granules and the nucleus cannot be seen. If the microscopist wishes to study details of the nucleus in any species he must "fix" the egg, i.e. kill and harden it with chemicals, and stain the nucleus with a dye solution.

However different the eggs of birds and of mammals may seem at first sight, they are fundamentally alike. Each is a single cell, with a nucleus no bigger than that of many of the ordinary cells of the body. The fact that the bird's egg is very large for a single cell, and that even the mammal's egg is the largest cell in the mammalian body, is due to the inclusion of a considerable amount of stored food substance in the cell. In the hen this yolk is enough to feed the chick until it hatches ; in mammals it is only a few grains of fat and protein, sufficient to provide energy for growth and cell division for a few days, until the fertilized egg reaches the uterus.

Plate VIII. Stages in the development of the Graafian follicle of the rat. Note the gradual enlargement of the cavity. In G the cells holding the egg to the wall of the follicle have begun to degenerate, and the follicle is ready to rupture. Magnified 60 times. From the Anatomical Record, by courtesy of J. L. Boling and the Wistar Institute of Anatomy and Biology.

Since the bird's egg needs protection from harsh external conditions — sunlight, dryness, a rough nest - it is provided with a hard shell secreted about it by the oviduct after it leaves the ovary. The mammalian egg, which is destined not to leave a soft, moist, dark environment within its mother until it is ready for birth, has no shell at all. The clear zone that surrounds it is comparable with the shell membrane of the hen's egg, familiar to everyone who has peeled the shell off a boiled egg. The bird's egg also receives in the oviduct, before the shell is laid on, a layer of albumen ("white of egg") which no doubt helps to cushion the yolk and has some nutritive value for the growing embryonic bird, but is chiefly important because of its property of holding water and thus preventing the egg from drying out by evaporation through the shell. This is another protection the mammalian egg does not require. It is therefore much smaller than the bird's egg, because, in the first place, it lacks these massive provisions for independent existence ; but also for a positive reason which my mathematically minded readers may have perceived. The mammalian egg, after only a few days of total dependence upon its paltry yolk, gets its nourishment by absorption of food and water by diffusion through its surface from the uterine fluid in which it reposes. How much it gets depends upon the area its surface presents to its surroundings. How much it needs depends upon its volume. Geometry teaches that as dimensions increase, surfaces increase as the square of the radius, but volumes increase as the cube. As organic bodies increase in size, therefore, the ratio between volume and surface becomes less favorable. This rule, which has been invoked to explain why animals do not grow to limitless dimensions, probably operates also to keep all sorts of cells, including eggs, within effective limits of size.

The fate of unfertilized eggs

Not all the eggs formed in the ovary, nor even a large proportion of them, go on to reach fruition. Most domestic mammals shed eggs from the ovary at regular intervals, the human one egg per month approximately, the guinea pig four or five eggs every fifteen days, the sow an average of about a dozen every twenty-one days. If there is no mating in a given cycle, those eggs proceed to degenerate while in the oviduct. Others degenerate in the ovary, sometimes even before well-developed follicles have formed about them, sometimes in large follicles. When this happens, the follicle also ultimately degenerates and disappears from the ovary. Such follicles are shown in Plate VII, A, B.

A Swedish investigator, Haggstrom, who counted the eggs in both ovaries of a 22-year-old woman, found about 420,000. Yet a woman who sheds one egg per month without interruption by pregnancy or illness during her entire life, from say the 12th to the 48th year, cannot use up more than 430-odd eggs. 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 3-weekly cycle ; but she has vastly more than this in the ovaries at birth. Whether or not there is new formation of eggs during adult life (as we discussed above), there is evidently a large overproduction of eggs in the ovaries. This, and a corresponding but enormously greater overproduction of sperm cells, is thought to be a survival from earlier evolutionary stages when germ cells were discharged into the water to take the risk of enemies and mischance.

When the reproductive period of life is over, there are still many eggs in the ovaries. These gradually diminish in number, but some of them may persist to advanced ages.

The corpus luteum

When the eggs of a frog or fish are spawned into the water the ovary has done its work. There is nothing more it can do for the eggs. It shrinks back to the insignificant bulk it had before the eggs began to ripen and nothing more is heard from it until the next breeding season. Not so in the mammals. Their eggs are not thrust into the outside world. The mother is still intimately responsible for them; they must be nourished and sheltered within her for weeks or months to come. The uterus is to be altered to receive them and keep them while they develop, the mammary gland must be signaled to grow and prepare milk for them when they are born. The ovary still has ahead of it the task of getting these things done.

The Graafian follicle therefore does not shrivel away after shedding the egg. Indeed, it has scarcely had time to collapse before it is being transformed into a corpus luteum (Fig. 9) and begins to function as an organ of internal secretion for the benefit of the embryo. The accompanying illustrations (Plate IX) give an idea of the situation and appearance of the corpus luteum. This remarkable change is brought about by growth of the cells that lined the cavity, which become so much larger that the inner wall of the follicle, folded by its collapse, becomes thick and firm and converts itself into a glandular body occupying the site of the follicle (Plate IX, Ai B). As the lining grows thicker, blood vessels creep in from the surrounding part of the ovary and make a network that carries blood past every one of the large cells (Plate IX, C). These cells become laden with a peculiar kind of fatty material, and in animals whose fat is yellowish, for example the cow, the transformed follicles are bright yellow in hue, becoming indeed just about the most brilliantly colored objects in the whole body. For this reason they were long ago named corpora lutea, yellow bodies ; but in animals whose body fat is white, as the sow, sheep, rat, and rabbit, they appear pink or whitish. The human corpus luteum forms a mass almost three-quarters of an inch in diameter, with a folded wall, bright orange in color, about a grayish core of fibrous tissue.

The corpus luteum in the ovaries of rabbit A monkey

Fig. 9. Diagram illustrating the structure and history of the corpus luteum.

Animals which shed one egg at a time have, of course, only one corpus luteum in each cycle of the ovary ; animals which bear multiple litters have a corpus luteum for each egg, i.e. for each follicle that ruptured. The sow averages ten corpora lutea in a batch, and may have twenty-five, which is the number of the largest litter of pigs ever recorded. The rat can have eighteen, the guinea pig two to four, dogs of various breeds as many corpora lutea as there are puppies in the litter of the breed.[3]

These yellow bodies of the ovary have been puzzling to scientists ever since they were first described by Regner de Graaf in 1672. A French medical student who wrote a thesis about them in 1909 listed twenty-five different incorrect hypotheses about their function; but already in 1898 LouisAuguste Prcnant had suggested that they might be glands of internal secretion, making some sort of hormone for the benefit of the eggs with which they are associated. Now that we know more about such glands, any microscopist can see that the corpora lutea have the signs of endocrine function written all over them. The large, imposing cells, built into a mass that communicates with the rest of the body only by the blood vessels ; the delicate texture, scarcely supported by connective tissue; the wealth of blood supply that reaches every cell - these are the telltale evidences that the corpora lutea are indeed organs of internal secretion, and that whatever product they secrete must be poured into the blood and carried away to exert its effect upon some other organ. The full story of the corpus luteum hormone, as we know it now, will be told in Chapter V.

The life of the corpus luteum is relatively short. If the egg is fertilized, the corresponding corpus luteum persists through the greater part, if not all, of pregnancy. If the egg is not fertilized, the corpus luteum has an active life of only about two weeks before it begins to degenerate. In the human cycle of four weeks a fresh corpus luteum is present, therefore, about half the time. The older corpora are visible in various stages of degeneration. Five or six months after the formation of a corpus luteum all traces of it have disappeared.

Plate IX. The corpus luteum of the Rhesus monkey. A, ovary split inty two parts and laid open to show the corpus luteum. Magnified 4 times. Courtesy of C. G. Hartman. B, section through ovary showing a large corpus luteum (Corner collection, no. 187). Magnified 10 times. C, small part of corpus luteum, magnified 250 times to show the cells. The narrow clear spaces between the cells, bordered by small dark nuclei, are capillary blood vessels. At the left 6 cells and parts of a blood capillary have been outlined with ink to show how each cell is in contact with a blood vessel.

The oviducts

When an egg is discharged from the ovary, it is received into the open end of one of the two oviducts y tubular conduits, each (in the human species) about 11.5 centimeters (43^ inches) long (Plates V and X). Medical men and the general public usually call them "Fallopian tubes," although Gabriele Fallopio (1523-1562) was not the first to mention them and had no idea of their real function ; he thought they were ventilators to let noxious vapors out of the uterus. The walls of the oviducts are made, like the intestines, of involuntary muscle cells. Their lining is a velvety membrane which follows their channel all the way to the uterus and joins the lining of that organ. The cells on the surface of this membrane are beset with fine hairlike processes ("cilia") lashing continuously downward, and thus producing a current through the oviducts toward the uterus. These cilia may be seen in Plate X, E. At their free ends, near the ovaries, the oviducts open directly into the abdominal cavity by handsome trumpet-shaped expansions with fringed edges covered by the velvety red lining tissue. One of the fringes of each oviduct runs right on to the ovary.

When we say the oviduct opens into the abdominal cavity, we must not forget that the "cavity" is actually packed full of intestines. When an egg escapes from the ovary, it does not pop into a large vacant space ; it merely glides in a thin film of moisture between the smooth surfaces of the organs in the region of the ovary. The open funnel of the oviduct is directly at hand, and moreover the moisture in which the egg drifts is constantly drawn into the oviducts, carrying the egg with it, by action of the cilia mentioned above. Small particles of carmine or even foreign eggs, introduced into the lower abdominal cavity by the experimenter, are within a few hours carried down the oviducts toward the uterus.

Plate X. A (at top), oviduct (Fallopian tube) of Rhesus monkey, drawn by J. F. Didusch from preparation by author. Enlarged 4 times. B, photograph of living eggs of a mouse, in passage through the oviduct. The eggs are seen through the walls of the oviduct, which is exceedingly thin in this small mammal. Magnified about 45 times. Courtesy of H. O. Burdick. C, model of a part of the oviduct of a rat, showing eggs in passage. Magnified about 33 times. From an article by G. C. Huber, by courtesy of the Wistar Institute of Anatomy and Biology. D, diagram showing comparative size of the egg of the rabbit and the folds of the lining of the oviduct. Courtesy of G. H. Parker. E, comparative size of the human egg and the cilia of the lining cells of the oviduct. The cilia are seen as little brushlike clumps on the free ends of some of the tall cells. Enlarged 600 times. This drawing was made by combining part of a human egg described by Warren H. Lewis (see Plate VII, D) with a picture of the epithelium of the oviduct from a paper by F. F. Snyder in the Bulletin of Johns Hopkins Hospital.

It is even possible for the egg to drift across from one ovary to the opposite oviduct, a distance of roughly 3 or 4 centimeters (1 to 2 inches), and therefore a woman who has had one ovary and the opposite Fallopian tube removed is not necessarily sterile. In some animals, e.g. the sow, the oviduct expands into a voluminous sac partly enclosing the ovary; in the dog and cat the enclosure is almost complete; in the rat and mouse it is quite complete and eggs are obliged to travel down the oviduct corresponding to the ovary from which they came.

How are the eggs transported? We know that this trumpetlike capsular part of the oviduct, just mentioned, throws itself during life into squirming movements which are especially active at the time the eggs are discharged. This may help draw the eggs into the oviduct. How they are pushed along toward the uterus, once they are in the tubular canal of the oviduct, is at present under discussion. When there are several eggs (that is, in animals which bear several young at a time) the eggs travel together at first, sticking together in a little web of cellular debris they have brought with them from the ovary, but after a few hours this entanglement dissolves and the eggs travel free and bare, though still more or less closely together. As will be seen from Plate X, C, Dy the lining of the tubes forms voluminous folds, so that the available space is hardly larger than necessary to permit passage of the eggs. It used to be thought without question that the eggs are brushed along by action of the lashlike cilia of the surface cells. This is still not out of the question, in spite of the relatively small size of the cilia as compared to the eggs — about in the proportion of an eyelash to an orange (Plate X, jE). With a bunch of eyelashes or something similar, for example a tiny camel's hair brush, it does not take much effort to roll along an orange floating in water, as the eggs float in the fluid contents of the oviduct.

This supposition, however, has its weak points. In the first place there are animals in which the oviduct is not provided with cilia throughout its entire length. In the second place, there is a remarkable fact which cannot easily be explained on the basis of ciliary transport, namely that the oviducts of different species of animals are of very different lengths, and yet with only a few known exceptions, the eggs make their journey through them in about the same time, reaching the uterus in 3 to 3% days. The oviduct of the sow is about forty times as long as that of the mouse, therefore the eggs must travel forty times as fast. The cilia, however, certainly do not beat that much more rapidly.

What is more, the cilia beat with more or less uniform motion, while the eggs do not travel at uniform speed. A former colleague of mine. Dr. Dorothy Andersen, once collected at a packing house a very large number of oviducts of swine containing eggs. She cut up each one into 5 segments and examined each segment separately to see whether it contained eggs. She found that it is common to find eggs in the middle segments, but rare to find them in the first and in the last parts of the tube - in other words, the eggs are rushed through the first fifth, transported very slowly through the middle stretch, and then hurried through the last part into the uterus. A similar and even more accurate observation has since been made in the mouse (W. H. Lewis and Wright).

All these difficulties lead us to suppose that the eggs are really transported by contractions of the muscle fibers in the walls of the oviducts, which move them along by a "milking" action. Such a mechanism is common in the body. That is how food is shoved along in the intestines. That is how a horse gets water through his esophagus up to his stomach when his mouth is away down in the pond. Similar contractions of the walls of the ureter force urine from kidneys to bladder, no matter what position the body may be in with respect to gravity. We know that the muscular walls of the oviducts undergo contractions which could move the eggs, and we know also that these contractions are under the influence of the hormones of the ovary, changing their rhythm and intensity at the very time the eggs are in transport. Burdick, Pincus, and Whitney have been able to lock the ova in the oviducts by administration of an ovarian hormone. Most students of this problem now think, therefore, that the chief method of transport of the eggs is by rhythmic contractions of the tubal muscles, and that the cilia play at most only a secondary role.

I have long thought that we ought not to emphasize the oviduct solely as an organ for transporting the ova, but rather as a means of delaying their transportation. We are going to see (in Chapter V) that the mammalian embryo, reaching the uterus naked, delicate, and yolkless on the fourth day after leaving the ovary, requires immediate nourishment and a soft succulent place in which to grow. The uterus must have time to get ready for its exigent tenant. If the embryos arrive too early they cannot develop. I believe that one of the most important functions of the oviduct is to hold back the eggs until the uterus is ready for them.

The uterus

When the eggs pass from the oviduct into the uterus they find themselves in a chamber of larger size, with heavier and more muscular walls.

The uterus is built on fundamentally the same plan in all mammals, although its form varies a great deal in different species. It consists basically of two tubular canals, one right and one left, corresponding to the two ovaries and oviducts.

Fig. 10. Form of the uterus in a series of mammals, illustrating the various degrees to which the two horns of the uterus are separate or fused. Ay monotreme (Echidna); B, marsupial (opossum); C, rodent (rabbit); D, carnivore (dog); E, ungulate (mare); F, primate (Rhesus monkey). From Physiology of the Uterus, with Clinical Correlations, by S. R. M. Reynolds, by courtesy of the author and Paul B. Hoeber, Inc.

Each canal is really the continuation of one of the oviducts. At their lower ends the uterus enters the last part of the genital tract, namely the vagina. In most animals the two canals of the uterus unite before they enter the vagina, forming a Y-shaped organ, with a single stem and two horns (Fig. 10, E), but the extent of this fusion differs very much in different animals. In rabbits the two horns remain entirely separate and enter the vagina independently, side by side (Fig. 10, C). In monkeys, apes, and humans the opposite extreme is found, for even the horns fuse together, closing the Y and making a single-chambered uterus into which the two oviducts are inserted as shown in the diagram, Fig 11.

Fig. 11. Diagram of the human female reproductive tract. The uterus, and the oviduct at the right, are depicted as if laid open by removing the nearer half. The vagina is drawn as if fully distended. In part after a drawing by R. L. Dickinson in his Human Sex Anatomy.

Even in these animals, however^ the uterus is double in its embryonic development. In Rhesus monkeys (Fig. 10, F) and in human infants there is a little notch at the top of the organ, marking the last trace of the doubling. In the other species shown in Fig. 10, namely echidna (A), opossum (B), dog (D), and mare {E) we find various degrees of fusion of the two horns. Sometimes in women the process of fusion fails to be completed, leaving a bicornuate (twohorned) uterus which under certain circumstances may puzzle the gynecologists or even be mistaken for a tumor. In a general way it may be said that animals which bear a single infant, or twins, at one time, have one-chambered uteri or short uterine horns, while those that bear multiple litters have well-separated horns. I hardly know which of these types offers the most striking picture, late in pregnancy when the uterus reaches its largest dimensions - the human, for example, with its infant ensconced in a single huge chamber, the cow with an unborn calf in one enormous sac with a little empty horn beside it, or a sow with two long uterine horns each distended like two great strings of sausage, with five to eight 12-inch pigs in each link.

The lining of the uterus

The longest act of the drama of reproduction is played in the cavity of the uterus. From the first week after the egg is shed from the ovary, until the day of birth, the infant knows no other environment, and depends absolutely upon the reactions of growth and chemical exchange that take place in these walls that shut it off from everything else in the world. Here occur, as we shall see, some of the most remarkable and important interactions of the hormones of the ovary and the tissues that guard the embryo, and here is the seat of the process of menstruation, strange phenomenon that is an outward sign of human participation in the cosmic tides.

Because the inner layer or lining of the uterus and what goes on in it will occupy much of this book, we may as well introduce its technical name at this point, to save printing two words for one every time it is mentioned: endometrium, from Greek endo, within, and metron, the uterus. It is a layer about 5 millimeters (1/5 inch) thick, lining the cavity and therefore applied to the inner surface of the pear-shaped muscular parts of the organ. At the upper end of the uterus it blends with the lining of the oviducts as they enter, at the lower end it continues on to become the lining of the vagina. It looks rather like pink or red velvet, slightly moistened. In most animals it is thrown into delicate folds, but in the human uterus it is relatively smooth. Upon the cells and secretions of this layer the embryo is to depend for everything it needs during gestation.

It is always difficult to convey in nontechnical terms an idea of the finer structure of the tissues of the body. In a book for general readers, microscopical anatomy is like mathematics in books on astronomy or physics — something to be avoided if possible. Yet physiology without cell structure means less than Einstein without calculus. Therefore let us buckle down together for a few pages and try to build up a picture of the cell structure of the endometrium for subsequent use.

The effort would be much easier if we could sit down together in my laboratory and prepare a specimen as shown in Fig. 12. Taking a preserved human uterus from a jar of formalin, we cut it in two lengthwise with a sharp knife so that we can look into the cavity (Fig. 12, A). Then we cut out a horizontal slab of uterine tissue {B) and from this we detach a little block running down through the endometrium into the muscle (C). This we shall place on the table, so that its upper side will be that which formed the surface of the lining, facing the cavity; i.e. like a cube of melon with the rind downward and the pulp upward (Fig. 12, C). After we have studied and sketched it under low magnification, we shall cut off a very thin slice (technically section) from one side, stain it with appropriate dyes and photograph it through the microscope (Plates XVII, XXI). When studying the two-horned uteri of small animals such as the rat, rabbit, or guinea pig, we usually cut our blocks from the whole thickness of the tubular horns, as one slices a banana, and therefore the thin sections for microscopic study are round, with the uterine cavity showing in the center (see Plate XVII, B, in comparison with A of the same plate).

Fig. 12. Block diagram showing construction of the lining of the uterus (endometrium). At A the uterus is represented as if cut in two lengthwise, to show its lining. At B is shown a block cut from the uterus ; a small part of this is represented at C, turned so that the inner surface of the endometrium is upward, showing the glands. At D a small part of C is drawn still more enlarged, to show that the glands are really cell-lined tubes dipping down from the surface epithelium.

We find that the surface is paved with a single layer of tall cells, and that at frequent intervals this surface layer pushes down into the depth of the endometrium, forming fingerlike tubes, closed at the end, which reach almost to the muscle (Fig. 12, C, D). These tubes are supported by spongy connective tissue, and between them there is a network of capillary blood vessels supplied by arteries. They are in fact actually glands, able as shown in Fig. 13, to take water and the "makings" of nutritive substances from the blood vessels, build them up into foodstuffs for the early embryo, and discharge the resultant secretion into the cavity of the uterus. The endometrium is therefore something like a quick-lunch counter, with a supply of raw foods in the rear (in the blood stream), a row of cooks and waiters (the gland cells) and a line of customers (the cells of the embryo). The outfit does not however function in this way all the time; it secretes nutritive materials, practically speaking, only when an egg is likely to be present. How all this is regulated by the hormones of the ovary will be explained in Chapter V. To paraphrase a saying of Robert Boyle, the endometrium looks like so much velvet, yet there are strange things performed in it.

The cervix and vagina

The lower end of the uterus projects downward into the vagina as shown in Fig. 11. This part of the organ is known as the neck or cervix. Its lining is full of glands which secrete mucus.

The lowest part of the genital canal, the vagina, is lined with a membrane made of cells many layers thick (Plate XIII, A)f closely resembling the structure of skin, except that the latter is dry and somewhat scaly, while the vaginal lining is moist. The lining of the vagina, in fact, becomes continuous with the skin of the outside of the body, at the vaginal orifice, just as the membranes of the nose, mouth, and lower intestine become continuous with the skin.

Fig. 13. Diagram representing a gland like those of the uterus, consisting of a tube of cells dipping down from the surface. This is surrounded by a network of capillary blood vessels, from which water and other substances pass through the gland cells, undergoing chemical elaboration, and are discharged into the central channel of the gland and thus reach the cavity of the uterus.

Fertilization and segmentation of the egg

Sperm cells deposited in the vagina by the male make their way up through the canal of the cervix and body of the uterus and into the oviduct. This journey is accomplished in a few hours, so that the descending egg and the ascending sperm cells meet in the Fallopian tube. There the process of fertilization takes place by entry of one sperm cell into the egg, as described for the sea urchin in the last chapter.

The egg now begins to divide. The process of division has not yet been observed in the human egg, but it has been well studied in many animals by the drastic and expensive method of killing animals at successive stages, a few hours apart, after mating so that the eggs can be found and studied under the microscope. In recent years the dividing eggs of rats, mice, rabbits, and monkeys have, through the skill of Warren H. Lewis of the Carnegie Embryological Laboratory and his various associates, been successfully removed, kept in dishes of salt solution at body temperature, and photographed in motion pictures. Our illustration (Plate XI) is taken from an excellent series of still photographs of the rabbit egg taken by P. W. Gregory in the same laboratory. To those who have not seen such pictures, this series will cause surprise chiefly by its resemblance to the dividing sea urchin eggs of Dr. Ethel Browne Harvey's series (Plate IV).

In most mammals the embryos pass from the oviduct to the uterus late on the third day or on the fourth. There is some reason to think the same is true in the human. By this time the embryos are at least in the four-cell stage and in some animals (e.g. the rabbit) they have divided even more fully, entering the uterus as little clumps of cells called morvlae from the Latin word for mulberry which they resemble. The embryo soon becomes a hollow sphere, with a little mass of cells at one side (Plate XI, J and K), This inner cell mass is to become the embryo proper ; the remainder of the spherical cyst becomes the embryonic membranes.

Plate XI. Division of the fertilized egg of the rabbit. A, one cell stage. B, two cell stage, 25 hours after mating. C, four cells. D to G', 4 to 32 cells. H, morula stage (solid mass of cells). /, first signs of hollowing. /, K, hollow stages (blastocysts) 90 and 92 hours after mating. Magnified about 140 times. From Contributions to Embryology, Carnegie Institution of "Washington, by courtesy of P. W. Gregory.

During the first few days after arrival in the uterus the embryos are free and unattached. In animals bearing only one infant at a time, as usual in the human species, the embryo simply settles down somewhere on the inner wall of the uterine cavity. Species bearing several young have long uterine horns to provide room for them all. In such animals the free embryos must be moved along the uterus, by a kind of squirming movement of the uterine walls, until they are spaced at regular intervals.


Attachment or implantation begins, in most species, about the 7th day, but in some (e.g. the sow) as late as the 13th. The nature and extent of the attachment of infant to mother, though fundamentally the same in all mammals, varies a good deal, in its structural character, in the various orders of the Mammalia. In the ungulates (hoofed animals), for instance, the attachment is not very intimate. In the sow the voluminous membranes of the embryos are simply apposed to the inside of the uterus, like a string of crumpled bags fitted inside the long uterine horns, and the embryos get their nutritive fluids and the oxygen they breathe, by filtration through these apposed membranes. When the pigs are born the membranes ("afterbirth") simply peel off the lining of the uterus leaving the latter more or less intact. In most mammals, however, the contact becomes much more intimate. The membranes send down long rootlike processes into the uterine lining or endometrium. This is illustrated in the diagram of the rabbit's implantation (Fig. 14). In the human and a few other animals, the early embryo settles down not merely on the inner surface of the uterus, but actually burrows down into the lining, and sends out its rootlike processes (villi) all about it. As it grows it bulges into the uterine cavity, remaining rooted at its base, and thus forms a definite organ of attachment, the placenta. The sketch, Fig. 14, gives a diagrammatic idea of this arrangement, and Plate XII illustrates some of the details of implantation in man and monkey, from the unique specimens of the Carnegie Embryological Collection.

Plate XII. Implantation of the embryo in the primate uterus. A embryo of Rhesus monkey (Carnegie C. Template:CE610) in the blastocyst stage, 9 days old, just settling down on the lining of the uterus. The little white spot in the center is the "inner cell mass," destined to become the embryo proper. Magnified 60 times. B, human embryo about 12 days old (Carnegie 7700) which has burrowed into the uterine lining. Magnified 12 times. C, section of a very similar human embryo (Carnegie 7802) showing how it lies within the endometrium. The glands of the uterus are in a state of progestational proliferation under the influence of the corpus luteum hormone (see Chapter V), Magnified 10 times. D, portion of same section magnified 30 times, to show the embryo proper {emh.) and the placental villi, which are beginning to grow out from the envelope (chorion) of the embryo. A by courtesy of G. L. Streeter, C. H. Heuser, and C. G. Hartman ; B, C, and D, by courtesy of A. T. Hertig and John Rock. Photographs by Chester Reather.

Fig. 14. Diagrams showing implantation of the embryo, in the rabbit and human. In the rabbit figures the uterus is represented as if cut transversely, as one slices a banana; in the human figures the uterus is cut lengthwise as one halves a pear. From Attaining Manhood, by George W. Corner, by courtesy of Harper and Brothers.

Within the placenta, blood vessels of the embryo ramify in close proximity to the blood stream of the mother. Nutritive substances and oxygen filter from the uterus through these blood vessels into the infant's blood; waste substances and carbon dioxide filter out. The infant, completely immersed in the fluid contents of its dark chamber, thus gets only such substances as can be brought to it dissolved in the mother's blood and filtered through the placenta.

Preparation of the uterus for implantation

It may make the next chapters clearer if we anticipate slightly at this point our discussion of the corpus luteum hormone (Chapter V). While the embryo is floating into the uterus prior to its attachment, it requires nourishment from the uterus. To provide this, and also to favor the invasion of the maternal tissues by the placenta, the hormone made by the corpus luteum (progesterone), acts on the uterus, causing great activity and growth of its tubular glands. Without this preparation the embryo, arriving in the uterus, would be unable to develop, like the seed told of in the Biblical parable, that fell on stony ground.

  1. The human ovary is about 3 centimeters (1.25 inches) long. The ovary of a mouse is hardly bigger than a pinhead, while that of a whale weighs 2 or 3 pounds; but their eggs are all about the same size, as we shall see.
  2. George W. Corner, "The Discovery of the Mammalian Ovum," Mayo Foundation Lectures in the History of Medicine, 1930.
  3. There are interesting exceptions to the statements in the foregoing paragraph. In the first place, human females occasionally shed two eggs at one time; if both are fertilized twins will be produced. In the case of identical twins there is only one egg, which forms two infants. Triplets usually come from two eggs, one of which gives twins. In the case of the Dionne quintuplets it is conjectured from indirect evidence (i.e. the close resemblance of the 5 sisters) that they all came from one egg. In animals with multiple litters it is often the case that not all the fertilized eggs develop successfully; then obviously there will be more corpora lutea in the ovary than infants in the litter. On the other hand it is possible, though uncommon, to have more infants than corpora lutea, for one follicle may contain two eggs (a rare event) or one or more of the eggs may develop into single-ovum twins.

   Hormones in Human Reproduction (1942): 1 Higher Animals | 2 Human Egg and Organs | 3 Ovary as Timepiece | 4 Hormone of Preparation and Maturity | 5 Hormone for Gestation | 6 Menstrual Cycle | 7 Endocrine Arithmetic | 8 Hormones in Pregnancy | 9 Male Hormone | Appendices
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