OVARY
The ovary is a combined exocrine and endocrine gland; that is, it produces both ova (exocrine “secretion”) and ovarian hormones, chiefly estrogens and progesterone (endocrine secretion). The structure of the normal ovary varies greatly with the species, age, and phase of the sexual cycle. It is an ovoid structure divided into an outer cortex and an inner medulla (Fig. 13-1). In the mature mare, these areas become reversed, and the cortical tissue remains on the surface only in the ovulation fossa, which is the site of all ovulations.
Cortex
The cortex is a broad peripheral zone containing follicles in various stages of development and corpora lutea embedded in a loose connective tissue stroma (Fig. 13-1). It is covered by a low cuboidal surface epithelium. A thick connective tissue layer, the tunica albuginea, lies immediately beneath the surface epithelium. It is disrupted by the growth of ovarian follicles and corpora lutea and may be inconspicuous during increased ovarian activity. In the ovary of rodents, bitches, and queens, the cortical stroma contains cords of polyhedral interstitial endocrine cells. In the ovary of bitches, cortical tubules are also prominent; these are narrow channels lined by a cuboidal epithelium that, in some sites, are continuous with the surface epithelium.
Follicular Development
An ovarian follicle is a structure composed of an oocyte surrounded by specialized epithelial cells; during follicular development, the epithelial cells become surrounded by specialized stroma cells and a fluid-filled cavity develops among the epithelial cells.
Primordial (unilaminar, preantral, resting) follicles are composed of a primary oocyte surrounded by a simple squamous epithelium of follicular cells (Figs. 13-1 and 13-2). Primordial follicles arise prenatally by mitotic proliferation of internal epithelial cell masses in the ovarian cortex. In some species (e.g., bitches), they may arise also postnatally. The internal epithelial cell masses are believed to arise after interaction of cortical stroma, ovarian surface epithelium, or irregular epithelioid cell cords or channels, termed rete ovarii, with primordial germ cells (PGCs); the PGCs arrive in the gonadal ridge from the wall of the yolk sac. During proliferation, the internal epithelial cell masses become separated into cell clusters. The central cell of a cluster becomes the oogonium. The oogonia enlarge, enter the prophase of the first meiotic division, and are then termed primary oocytes, approximately 20 µm in diameter in most species. The primary oocytes then go through the leptotene, zygotene, pachytene, and diplotene stages and then remain in the dictyotene stage. As the primary oocyte forms, the surrounding cells form a single layer of flat follicular cells resting on a basal lamina. Together, these components constitute the primordial follicle, approximately 40 µm in diameter. Primordial follicles are located mainly in the outer cortex. They are evenly distributed in ruminants and the sow and occur in clusters in carnivores.
FIGURE 13-1 Ovary of queen showing the development and the regression of follicles and corpora lutea in the ovarian cortex. The ovarian medulla contains blood vessels (a) that enter the ovary at the hilus from the mesovarium (a′). Surface epithelium with adjacent tunica albuginea (b); subtunical layer with primordial follicles (c); primary follicles (d); secondary follicle (e); tertiary follicles, in one case containing an oocyte within the cumulus oophorus (f); early atretic follicle (g); corpora lutea (h); corpus regressivum (i); interstitial endocrine cells (k) (×56).
FIGURE 13-2 Ovary of queen showing primordial follicles (a), which consist of primary oocytes surrounded by a simple squamous epithelium. Nucleus with nucleolus (b). Primary follicle (c), in which a cuboidal epithelium (d) encloses an enlarged primary oocyte (e). Interstitial endocrine cells containing granules (f ) are seen near capillaries (g) (×300).
Primary (unilaminar, preantral, growing) follicles are composed of a primary oocyte surrounded by a simple cuboidal epithelium of follicular cells (Figs. 13-1 and 13-2). The primary oocytes begin the first meiotic division before birth, but the completion of prophase does not occur until the time of ovulation. The primary oocytes thus remain in suspended prophase (dictyotene stage) until after puberty. Several hundred thousand to 1 million potential oocytes may be present at birth in a single ovary in various species. Most of these regress before or after birth, and only several hundred ovulate during a normal lifetime. The processes involved in the selection of follicles for growth from a pool of non-proliferating primordial follicles are poorly understood.
Secondary (multilaminar, preantral, growing) follicles are composed of a primary oocyte surrounded by a stratified epithelium of polyhedral follicular cells, termed granulosa cells (Figs. 13-1 and 13-3). The multilaminar stratum of granulosa cells arises from proliferating follicular cells of the primary follicle. In carnivores, sows, and ewes, polyovular follicles, which contain several oocytes, may develop. In cows, the late secondary follicle is approximately 120 µm in diameter and contains an oocyte approximately 80 µm in diameter. Secondary follicles are marked by the development of a 3- to 5-µm-thick glycoprotein layer, the zona pellucida, around the plasma membrane of the oocyte (Fig. 13-3). The zona pellucida is secreted by the granulosa cells immediately surrounding the oocyte and, in part, by the oocyte itself. There is partial penetration of this zone by the oocyte microvilli. Cytoplasmic extensions of the granulosa cells situated around the oocyte penetrate the zona pellucida and associate closely with these microvilli. As follicular development continues, small fluid-filled clefts are formed among the granulosa cells. A vascularized multilaminar layer of spindle-shaped stroma cells, termed theca cells, begins to form around the granulosa cell layer in late secondary follicles.
FIGURE 13-3 Ovary of queen showing a secondary follicle, in which the primary oocyte (a) is surrounded by a thin (initially) zona pellucida (b) and a stratified epithelium of polyhedral cells (c), of which the inner cell layer forms the corona radiata (d). Call-Exner bodies (e) are present in some cells. The connective tissue cells that surround the follicle will form the theca interna (f ). Interstitial endocrine cells (g) are located in the connective tissue outside the follicle (×175).
Tertiary (multilaminar, antral, growing) follicles, also termed vesicular or Graafian follicles, are composed of a pri mary oocyte (or, immediately before ovulation, a secondary oocyte in most species) surrounded by a stratified epithelium of granulosa cells; the granulosa cells are surrounded by a multi-laminar layer of specialized stromal cells, termed the theca, and a fluid-filled cavity, the antrum, develops among the granulosa cells (Figs. 13-1, 13-4, and 13-5). The antrum, which characterizes tertiary follicles, is formed when the small, fluid-filled clefts among the granulosa cells of secondary follicles coalesce to form a single large cavity containing liquor folliculi. Late tertiary follicles, just before ovulation, are termed mature follicles (Fig. 13-6). In mature follicles, just before or just after ovulation, depending on the species, the primary oocyte completes the first meiotic division, thereby giving rise to a secondary oocyte and the first polar body.
FIGURE 13-4 Ovary of queen showing a tertiary follicle, which contains an antrum (a) and a multilayered epithelium, the stratum granulosum (b); a cumulus oophorus (c) enclosing the primary oocyte (d) forms in the stratum granulosum. The antrum contains a flocculent liquor folliculi. A connective tissue layer, the theca, which surrounds the stratum granulosum, can be divided into an inner theca interna, with light voluminous cells (e), and an outer theca externa, with dark fibrocytes (f). Marginal cells of the corpus luteum (g) have features of interstitial endocrine cells (h) (×110).
The primary oocyte in tertiary follicles measures 150 to 300 µm in diameter, depending on the species. It has a spherical, centrally located nucleus with a sparse chromatin network and a prominent nucleolus. The Golgi complex, initially dispersed in the cytoplasm, becomes concentrated near the plasma membrane. Lipid granules and lipochrome pigment occur in the cytoplasm. As the antrum enlarges through the accumulation of liquor folli culi, the oocyte is displaced eccentrically, usually in a part of the follicle nearest to the center of the ovary (Fig. 13-1). The oocyte then lies in an accumulation of granulosa cells, the cumulus oophorus (Fig. 13-4). In large tertiary follicles, the granulosa cells immediately surrounding the oocyte become columnar and radially disposed; they are termed the corona radiata (Fig. 13-5A). The corona radiata cells are believed to provide nutrient support for the oocyte. They are lost at the time of ovulation in ruminants but generally persist until just before fertilization in other species.
FIGURE 13-5 A. A bovine oocyte, surrounded by the zona pellucida (a), the corona radiata (b), and cells of the cumulus oophorus (c), is separated from the stratum granulosum of the follicular wall (e) by a gap (d) that developed during oocyte detachment from the follicle wall during the beginning stages of ovulation. Basal lamina of stratum granulosum (f); theca interna (g) (×220). B. An electron micrograph from the bovine ovary showing projections of a corona radiata cell (top) and of an oocyte (bottom), traversing a homogeneous zona pellucida, being in gap-junctional contact (arrow) with each other (×9000). (Courtesy of P. Hyttel. From Leiser R. Weibliche Geschlechtsorgane. In: Mosimann W, Kohler T, eds. Zytologie, Histologie und mikroskopische Anatomie der Haussäugetiere. Berlin: Verlag Paul Parey, 1990:232.)
In tertiary follicles, the granulosa cells form a parietal follicular lining, the stratum granulosum (Figs. 13-4 and 13-5A). Most of the parietal granulosa cells are polyhedral, but the basal layer may be columnar. Some of the granulosa cells in secondary and tertiary follicles may contain large periodic acid-Schiff (PAS) positive inclusions, the Call-Exner bodies, which represent intracellular precursors of liquor folliculi (Fig. 13-3). In the large tertiary follicle, the granulosa cells have the fine structural characteristics of protein-secreting cells, notably an extensive granular endoplasmic reticulum (ER). Before ovulation, the granulosa cells of the mature follicle assume the characteristics of steroid-secreting cells, especially an agranular ER and mitochondria with tubular cristae.
FIGURE 13-6 A. Ovary of sow with mature tertiary follicles immediately before ovulation (a) and one just ovulated as indicated by the stigma (b). A subepithelial vein (g) (×2.7). B. A schematic drawing of the follicle in A (left) shows the oocyte ready to disengage itself from the stratum granulosum at a site opposite the thinned, protruding follicular wall at the ovulation site, the stigma. Note the theca interna (c), theca externa (d), primordial follicles (e), primary follicle (f ), and blood vessels (g).
The stratum granulosum is surrounded by the theca, which in tertiary follicles differentiates into two layers: an inner vascular theca interna and an outer supportive theca externa (Fig. 13-6). The theca interna cells are spindle-shaped in early tertiary follicles and located in a delicate reticular fiber network. An extensive blood and lymph capillary network is present in the theca interna, but it does not penetrate the stratum granulosum. Sympathetic nerve endings are present around the larger follicles. In mature follicles, many of the spindle-shaped theca interna cells adjacent to the stratum granulosum increase in size and become polyhedral and epithelioid. The nuclei of the epithelioid cells have a lighter chromatin pattern and more distinct nucleoli than those of the spindle-shaped cells. Cytoplasmic organelles in the epithelioid cells become typical of steroid-secreting cells: the mitochondria with tubular cristae, agranular tubular ER, and lipid inclusions are present. The epithelioid cells are abundant in mature follicles during proestrus and estrus and during their early regression.
The theca externa consists of a thin layer of loose connective tissue with fibrocytes arranged concentrically around the theca interna. Blood vessels of the theca externa supply capillaries to the theca interna.
One or more mature follicles reach maximal development near the time of ovulation. The primary oocyte (containing a diploid number of chromosomes) in these follicles completes the first meiotic division to become a secondary oocyte (containing a haploid number of chromosomes). During the first meiotic division, chromosome pairs are established and a mixture of parental genetic material occurs. Separation of the pairs and the production of the secondary oocyte and the first polar body (also containing a haploid number of chromosomes but little cytoplasm) follow as the division is completed. In domestic animals, the first meiotic division is completed shortly before ovulation, except in the bitch and the mare, in which it is completed shortly after ovulation (i.e., a primary oocyte is ovulated in the bitch and the mare). The second meiotic division begins immediately after the first meiotic division is completed but is arrested in metaphase; it is not completed unless fertilization occurs. At fertilization, the second meiotic division is completed, the secondary oocyte becomes an ovum, and a second polar body (also with little cytoplasm) is given off. The ovum becomes a zygote when the male and female chromosomes come together, establishing a diploid number of chromosomes.
Ovulation
When the follicle is fully developed, it protrudes from the surface of the ovary. Abundant blood and lymph vessel networks surround the follicle and an increased rate of secretion of a thin liquor folliculi occurs. The increased secretion rate is facilitated by increases in the follicular blood capillary pressure and permeability during proestrus and estrus. The increased accumulation of liquor folliculi causes the follicles to swell, but intrafollicular pressure does not significantly increase. Small hemorrhages occur in the follicular wall. The follicular wall becomes thin and transparent at the future site of follicular rupture, the stigma. The mature ovulatory follicles attain a size of 15 to 20 mm in cows; 50 to 70 mm in mares; approximately 10 mm in ewes, goats, and sows (Fig. 13-6A); and approximately 2 mm in bitches and queens.
Changes in the wall of the follicle preceding rupture are caused by the release of collagenases. Luteinizing hormone (LH) stimulates the production of prostaglandins (PG) F2 and E2. PGF2 is believed to release collagenases from follicular cells, causing digestion of the follicular wall and its distension at the stigma. The process of digestion also releases proteins that provoke an inflammatory response with leukocytic infiltration and the release of histamine. All of these processes degrade the connective tissue of the follicular wall and the ground substance of the cumulus oophorus, so that the follicle ultimately ruptures at the stigma and the oocyte is released. The oocyte, usually surrounded by the corona radiata, escapes into the peritoneal cavity, from which it is swept directly into the infundibulum of the uterine tube. On rare occasions, an oocyte may fail to enter the uterine tube and, if fertilized, may establish ectopic pregnancy. In most species, the corona radiata cells disperse in the uterine tube in the presence of spermatozoa; in ruminants, they already are lost at the time of ovulation. The oocyte generally remains fertilizable for less than 1 day; when not fertilized, it degenerates and is resorbed. Most domestic animals ovulate spontaneously, but ovu-lation in queens is induced by a copulatory stimulus.
Follicular Atresia and Interstitial Endocrine Cells
Most follicles regress at some time during their development, and only a small percentage of all potential oocytes is ovulated from the ovary. This regression is called atresia; many more follicles become atretic than ever attain maturity. Prominent signs of atresia in follicular wall cells are nuclear pyknosis and chromatolysis. During atresia, the basal lamina of the granulosa layer may fold, thicken, and hyalinize; it is then called the glassy membrane (Fig. 13-7A). Eventually, atretic follicles are resorbed, except that small fibrous tissue scars may remain after atresia of large follicles.
In cows, in atresia of primary and secondary follicles, the oocyte commonly degenerates before the follicular wall, whereas in tertiary follicles, the reverse is true. Atretic changes in bovine tertiary follicles may result in the formation of two different morphologic types of atretic follicles: obliterative and cystic. In obliterative atresia, the granulosa and theca layers both infold, hypertrophy, and extend inward to occupy the antrum. In cystic atresia, both the granulosa and theca layers may atrophy, or only the granulosa layer may atrophy and the theca layer may luteinize, become fibrotic, or hyalinize around the antrum (Fig. 13-7B). In cystic atretic follicles, the theca interna cells containing LH receptors may continue to synthesize androgens after the regression of the granulosa cells, which converted the androgens to estrogens.
In the ovaries of the bitch, the queen, and rodents, interstitial endocrine cells are prominent; they arise chiefly from the epithelioid theca interna cells of atretic antral follicles or from hyper-trophied granulosa cells of atretic preantral follicles (Fig. 13-8). They are usually absent from the ovaries of other adult domestic animals. The interstitial endocrine cells are polyhedral and epithelioid and contain lipid droplets. In species such as rabbits and hares, they show an abundance of steroid-synthesizing organelles.
FIGURE 13-7 A. Atretic tertiary follicle (mature bitch). The oocyte (a) and granulosa layer (b) have degenerated, and the theca layer (c) has fibrosed. “Glassy membrane” (d) (×170). (With permission from Adam WS, Calhoun ML, Smith EM, et al. Microscopic Anatomy of the Dog: A Photographic Atlas. Springfield, IL: Charles C. Thomas, 1970.) B. Atresia of a large tertiary ovarian follicle (cow). Extensive hyalinization of theca interna (a) and loss or pyknosis of granulosa cells (b). Theca externa (c) (×100). (From Priedkalns J. Effect of melengestrol acetate on the bovine ovary. Z Zellforsch 1971;122:85.)
Corpus Luteum
At ovulation, the follicle ruptures, collapses, and shrinks as the liquor pressure is reduced. Folding of the follicular wall is extensive. The ruptured follicle is referred to as a corpus hemorrhagicum because of the blood that may fill the antrum. Bleeding after rupture of the follicle in mares, cows, and sows is greater than that in carnivores and small ruminants. Immediately before ovulation, some cells of the stratum granulosum exhibit signs of pyknosis. After ovulation, the stratum becomes vascularized by an extensive capillary network originating from blood vessels in the theca interna. The granulosa cells enlarge, luteinize, and contribute to the large luteal (lutein) cell population of the corpus luteum. Simultaneously, folding of the follicular wall results in the incorporation of the theca interna into the corpus luteum, and, in most species, the theca interna cells contribute initially to the small luteal (lutein) cell population of the corpus luteum.
FIGURE 13-8 Atretic tertiary follicle (queen). The former antrum (a) and the stratum granulosum (b) have fibrosed, and the theca (c) has been replaced by epithelioid interstitial endocrine cells (×230).
Luteinization is the process by which the granulosa and theca cells transform into luteal cells. It includes hypertrophy and hyper-plasia of both cell types. A yellow pigment, lutein, appears in the luteal cells in cows, mares, and carnivores; it is absent in ewes, goats, and sows. A black pigment has been observed in the luteal cells of mares. In cows, postovulatory mitosis lasts for approximately 40 hours in the granulosa luteal cells and for approximately 80 hours in the theca luteal cells. The increase in size of the corpus luteum, after the period of mitotic activity, results mainly from hypertrophy of the large luteal cells. The small luteal cells make up a minor part of the corpus luteum and occupy mainly trabecular and peripheral areas.
The large luteal cells are polygonal, measure approximately 40 µm in diameter, and have a large spherical vesicular nucleus. They contain numerous metabolic lipid inclusions (Fig. 13-9). During metestrus and diestrus, the cells contain organelles characteristic of steroid-synthesizing cells, such as mitochondria with tubular cristae and abundant tubular agranular ER (Fig. 13-9C). The small luteal cells have more lipids but fewer steroid-synthesizing types of organelles than do the large luteal cells (Fig. 13-9A and B). The two luteal cell types eventually become mixed in the corpus luteum and are then difficult to distinguish. They both produce progesterone. Progesterone receptor expression and associated messenger ribonucleic acid (mRNA) activity are evident in luteal cells, especially during metestrus and diestrus and in pregnancy, suggesting that luteal autoregulatory mechanisms have a role in progesterone production. In cows, the corpus luteum is fully developed and vascularized 9 days after ovulation but continues to grow until day 12, when it attains a diameter of approximately 25 mm.
The first sign of luteal regression is seen in late diestrus and involves the condensation of lutein pigment, which then appears reddish, followed by fibrosis and resorption of most of the corpus luteum. In cows, these signs are first observed 15 days after ovulation; further shrinkage of the corpus luteum occurs rapidly after day 18, and regression is complete 1 to 2 days after estrus. Large lipid droplets and crystalloid inclusions are typical of regressing luteal cells (Figs. 13-10 and 13-11). The vascular connective tissues of the corpus luteum become conspicuous in regression, with muscle cells in the walls of luteal arteries transformed by cellular hypertrophy and sclerosis. The connective tissue scar remaining after luteal regression is called the corpus albicans. In older ovaries, there is an abundance of such scars.
Medulla
The medulla is the inner area of the ovary containing nerves, many large and coiled blood vessels, and lymph vessels (Fig. 13-1). It consists of loose connective tissue and strands of smooth muscle continuous with those in the mesovarium. Retia ovarii are located in the medulla; they are solid cellular cords or networks of irregular channels lined by a cuboidal epithelium. They are prominent in carnivores and ruminants. It is claimed that the cells of the rete may differentiate into follicular cells when in juxtaposition to an oocyte.
Blood Vessels, Lymphatics, and Nerves
Arteries enter the ovary at the hilus. In the medulla, they form plexuses and give off branches to the follicular thecae, corpora lutea, and stroma. Around the larger follicles, arterial branches form a capillary wreath. During cyclic regression of the corpora lutea and the follicles, muscle hypertrophy and sclerosis occur in the walls of the arteries supplying these structures. The venous return is parallel to the arterial supply. Lymph capillaries accompany blood vessels in the follicular thecae and in the corpus luteum.
The nerves that supply the ovary are generally nonmyelinated. They are vasomotor in nature but include some sensory fibers. The nerves follow blood vessels and terminate in the walls of the vessels and around the follicles, in the corpora lutea, and in the tunica albuginea. They are derived mainly from the sympathetic system through renal and aortic plexuses, but vagal supply of the ovary also has been claimed.
UTERINE TUBE (OVIDUCT)
The uterine tubes are bilateral, tortuous structures that extend from the region of the ovary to the uterine horns and convey ova, spermatozoa, and zygotes. Three segments of the uterine tube can be distinguished: (a) the infundibulum, a large funnel-shaped portion (Fig. 13-12); (b) the ampulla, a thin-walled section extending caudally from the infundibulum (Fig. 13-13A); and (c) the isthmus, a narrow muscular segment joining the uterus (Fig. 13-13B).
FIGURE 13-9 A. Part of a mature corpus luteum (sow). The corpus luteum consists of large luteal cells (a) intermingling with groups of small luteal cells (b). The corpus luteum is supplied with blood vessels (c) entering from the periphery by the trabeculae (arrows). Ovarian surface epithelium (d); adjacent tunica albuginea (e) (×120). B. Enlarged segment of A showing large (a) and small (b) luteal cells containing fine granular inclusions and lipid droplets (f). Nuclei (g); capillaries (h); strand of connective tissue (i) (×830). C. Large luteal cell from a corpus luteum from the same ovary of the sow as in A and B. Nucleus (a); granular endoplasmic reticulum (b); tubular and smooth endoplasmic reticulum (c); Golgi complex (d); secretory granules (e); mitochondria with tubular cristae (f) (×15,700).
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
