Ovary

Ovary (ovarium, Greek oophoron) - paired organ, female genital gland, located in the cavity of the small pelvis behind the wide ligament of the uterus. Ovaries develop and mature female sex cells (ovules), as well as female sex hormones that enter the blood and lymph. The ovary has an ovoid shape, somewhat flattened in the anterior-posterior direction. The color of the ovary is pinkish. On the surface of the ovary of a woman giving birth, depressions and scars are visible - traces of ovulation and transformation of yellow bodies. The ovary mass is 5-8 g. The ovary dimensions are 2.5-5.5 cm long, 1.5-3.0 cm wide, and 2 cm thick. The ovary has two free surfaces: the facies medialis ), facing the cavity of the small pelvis, partly covered by the fallopian tube, and the lateral surface (facies lateralis), adjacent to the side wall of the small pelvis, to the slightly expressed depression - the ovarian fossa. This fovea lies in the corner between the peritoneal external iliac vessels at the top and the uterine and occlusal arteries at the bottom. Behind the ovary, the ureter of the corresponding side passes from the top to the bottom.

The surfaces of the ovary pass into the convex free margin (margo liber), in front to the mesenteric margin (margo mesovaricus), attached by a short fold of the peritoneum (ovary mesentery) to the posterior leaf of the broad ligament of the uterus. On this anterior edge of the organ is a grooved depression - the ovary gate (hilum ovarii), through which the artery and nerves enter the ovary, veins and lymphatic vessels exit. The ovary also has two ends: a rounded upper tube end (extremitas tubaria) facing the fallopian tube, and a lower uterine end (extremitas utenna) connected to the uterus by an ovary ligament (lig. Ovarii proprium). This bundle in the form of a circular strand about 6 mm thick goes from the uterine end of the ovary to the lateral corner of the uterus, located between two sheets of the broad ligament of the uterus. The ligamentous apparatus of the ovary also includes a ligament suspended from the ovary (lig.suspensorium ovarii), which is a fold of the peritoneum running from above the pelvic wall to the ovary, and containing inside the ovary vessels and bundles of fibrous fibers. The ovary is fixed with a short mesentery (mesovarium), which is a peritoneal duplication that runs from the posterior sheet of the broad ligament of the uterus to the mesenteric margin of the ovary. The ovaries themselves are not covered by the peritoneum. The largest ovary fimbria of the uterine tube is attached to the tube end of the ovary. The topography of the ovary depends on the position of the uterus, its magnitude (during pregnancy). Ovaries refer to very mobile organs of the pelvic cavity.

[1], [2], [3], [4], [5], [6]

Ovarian vessels and nerves

Blood supply to the ovaries is due to aa. Et vv. Ovaricae et uterinae. Both ovarian arteries (aa. Ovaricae dextra et sinistra) depart from the anterior surface of the aorta just below the renal arteries, the right more often originating from the aorta and the left one from the renal artery. Going down and lateral along the anterior surface of the large lumbar muscle, each ovarian artery crosses the ureter in front (giving it twigs), the outer iliac vessels, the border line and enters the pelvic cavity, located here in a suspending ligament of the ovary. Following in the medial direction, the ovarian artery passes between the leaves of the broad ligament of the uterus under the fallopian tube, giving it branches, and then to the mesentery of the ovary; enters the gates of the ovary.

The branches of the ovarian artery are widely anastomosed with the ovarian branches of the uterine artery. Venous outflow from the ovaries is carried out primarily in the ovarian venous plexus, located in the area of the ovary gates. Hence the outflow of blood passes in two directions: through the uterine and ovarian veins. The right ovarian vein has valves and runs into the lower vena cava. The left ovarian vein flows into the left renal vein, and there are no valves in it.

Lymph outflow from the ovaries occurs through the lymphatic vessels, especially abundant in the area of the organ gates, where the sublingual lymphatic plexus is excreted. Then, the lymph is diverted to the para-aortic lymph nodes along the ovarian lymphatic vessels.

Innervation of the ovaries

Sympathetic - is provided by postganglionic fibers from the celiac (solar), upper-braided and hypogastric plexuses; parasympathetic - due to the internal sacral nerves.

Structure of the ovary

The surface of the ovary is covered with a single-layered germinal epithelium. Underneath there is a dense connective tissue envelope (tunica albuginea). The connective tissue of the ovary forms its stroma (stroma ovarii), rich in elastic fibers. The substance of the ovary, its parenchyma, is divided into the outer and inner layers. The inner layer lying in the center of the ovary, closer to its gates, is called the medulla ovarii. In this layer in the loose connective tissue there are numerous blood and lymph vessels and nerves. Outer layer of ovary - cortex ovarii is more dense. It has a lot of connective tissue, in which ripening primary ovarian follicles (folliculi ovarici primarii), secondary (bladder) follicles (folliculi ovarici secundarii, s.vesiculosi), as well as mature follicles, folliculi ovarici maturis, as well as yellow and atretic bodies.

In each follicle is a female reproductive ovum, or oocyte (ovocytus). Ovary with a diameter of up to 150 μm, rounded, contains a nucleus, a large amount of cytoplasm, in which, in addition to cellular organelles, there are protein-lipid inclusions (yolk), glycogen necessary to feed the egg. Its oocyte supply usually consumes within 12-24 hours after ovulation. If fertilization does not occur, the egg dies.

The human ovary has two covering membranes. Inside is the cytolemma, which is the cytoplasmic membrane of the oocyte. Outside the cytolemma, there is a layer of so-called follicular cells that protect the egg and perform a hormone-forming function - they release estrogens.

The physiological position of the uterus, tubes and ovaries is provided by the suspending, fixing and supporting apparatus, Combining the peritoneum, ligaments and pelvic cellulose. The suspension device is represented by paired formations, it includes round and wide ligaments of the uterus, own ligaments and hanging ligamentous ovaries. Wide ligament of the uterus, own and suspending ligament of the ovaries keep the uterus in the middle position. Round ligaments attract the bottom of the uterus anteriorly and provide its physiological inclination.

The fixing device secures the position of the shaky in the center of the small pelvis and makes it practically impossible to shift it to the sides, back and forth. But since the ligamentous apparatus moves away from the uterus in its lower part, it is possible to incline the uterus in various directions. The ligamentous apparatus includes ligaments located in the loose cellular tissue of the pelvis and extending from the lower part of the uterus to the lateral, anterior and posterior walls of the pelvis: sacral-pulmonary, cardinal, uterine-vesicle and vesicular-pubic ligaments.

In addition to mesovarium, the following ovarian ligaments are distinguished:

• a suspension of the ovary ligament, formerly referred to as voronkotazovaya. It is a fold of the peritoneum with the blood (a et v. Ovarica) passing through it and the lymphatic vessels and nerves of the ovary, stretched between the side wall of the pelvis, the lumbar fascia (in the division of the common iliac artery into the outer and inner) and the upper (tubular) the end of the ovary;
• the ovarian's own ligament passes between the sheets of the wide uterine ligament, closer to the posterior sheet, and connects the lower end of the ovary with the lateral margin of the uterus. To the uterus, the ovary's own ligament is attached between the beginning of the uterine tube and the circular ligament, back and forth from the latter. In the thickness of the ligament are rr. Ovarii, which are the terminal branches of the uterine artery;
• appendicular-ovarian ligament The clade extends about the ridge of the appendix to the right ovary or the wide ligament of the uterus in the form of a fold of the peritoneum. The ligament is unstable and is observed in 1/2 - 1/3 of women.

The supporting apparatus is represented by the muscles and fasciae of the pelvic floor, divided into lower, middle and upper (inner) layers.

The most powerful is the upper (inner) muscle layer, represented by the paired muscle that raises the anus. It consists of muscle bundles that fan out from the coccyx to the pelvic bones in three directions (pubic-coccygeal, ilio-coccygeal and ischiococcygeal muscles). This layer of muscles is also called the diaphragm of the pelvis.

The middle layer of muscles is located between the symphysis, pubic and ischium bones. The middle layer of the muscles - the urogenital diaphragm - occupies the anterior half of the pelvic outlet, through it passes the urethra and the vagina. In the anterior part between its leaves are muscle beams forming the outer sphincter of the urethra, in the back part there are muscular bundles going in the transverse direction, the deep transverse muscle of the perineum.

The lower (outer) layer of the muscles of the pelvic floor consists of surface muscles, the shape of which resembles the figure 8. These include bulbous-cavernous, ischial-cavernous, external sphincter of the anus, surface transverse perineal muscle.

Ontogeny of the ovaries

The process of growth and follicular atresia begins with 20 weeks of pregnancy, and by the time of delivery in the ovaries of the girl remains up to 2 million oocytes. By the time of menarche, their number decreases to 300 thousand. During the entire period of reproductive life reaches maturity and ovulates no more than 500 follicles. The initial growth of follicles does not depend on stimulation of FSH, is limited, and atresia occurs quickly. It is believed that, in place of steroid hormones, the local autocrine / paracrine peptides are the main regulator of growth and atresia of primary follicles. It is believed that the process of growth and atresia of the follicles is not interrupted by any physiological processes. This process continues at all ages, including the intrauterine period and menopause, is interrupted by pregnancy, ovulation and anovulation. The mechanism that triggers the growth of follicles and their number in each specific cycle is not yet clear.

In its development, the follicle undergoes several stages of development. Primordial germ cells originate from the endoderm of the yolk sac, allantois and migrate to the genital area of the embryo at the 5th-6th week of pregnancy. As a result of rapid mitotic division, which lasts from 6-8 weeks to 16-20 weeks of pregnancy, up to 6-7 million oocytes are formed in the ovaries of the embryo, surrounded by a thin layer of granulosa cells.

The preantral follicle - the oocyte is surrounded by a membrane (Zona pellucida). Granulosa cells surrounding the oocyte begin to proliferate, their growth depends on the gonadotropins and correlates with the level of estrogens. Granulosa cells are the target for FSH. At the stage of the preantral follicle, granulosa cells can synthesize three classes of steroids: preferentially induces the activity of aromatase, the main enzyme that converts androgens to estradiol. It is believed that estradiol is able to increase the number of its own receptors, providing a direct mitogenic effect on granulosa cells independent of FSH. It is considered as a paracrine factor that enhances the effects of FSH, including the activation of aromatization processes.

FSH receptors appear on membranes of granulosa cells as soon as the growth of the follicle begins. Reduction or increase in FSH leads to a change in the number of its receptors. This action of FSH is modulated by growth factors. FSH acts via G-protein, adenylate-cyclase system although steroidogenesis in the follicle is mainly regulated by FSH, many factors are involved in this process: ion channels, tyrosine kinase receptors, phospholipase system of secondary messengers.

The role of androgens in the early development of the follicle is complex. Granulosa cells have androgen receptors. They are not only a substrate for FSH-induced aromatization in estrogens, but can enhance the aromatization process at low concentrations. When the androgen level increases, the preantral granulosa cells preferentially choose not the aromatization pathway to estrogens, but the simpler way of converting into androgens through the 5a-reductase, turning into androgen, which can not be converted to estrogen, and thus inhibits aromatase activity. This process also inhibits FSH and the formation of LH receptors, thus stopping the development of the follicle.

The process of aromatization, a follicle with a high level of androgens undergoes processes of atresia. The growth and development of the follicle depends on its ability to convert androgens into estrogens.

In the presence of FSH, the dominant substance of the follicular fluid is estrogens. In the absence of FSH - androgens. LH is normal in the follicular fluid until the middle of the cycle. As the level of LH increases, the mitotic activity of the granulosa cells decreases, degenerative changes appear and the level of androgens in the follicle increases. The level of steroids in the follicular fluid is higher than in the plasma and reflects the functional activity of the ovary cells: granulosa and teca cells. If the only target for FSH are granulosa cells, then LH has many targets - these are the cells, stromal and luteal cells and granulosa cells. The ability to steroidogenesis has both granulosa and teka cells, but aromatase activity predominates in granulosa cells.

In response to LH, teka cells produce androgens, which then, through FSH-induced aromatization, are transformed by granulosa cells into estrogens.

As the follicle grows, the current cells begin to express genes for LH receptors, P450 sec and 3beta-hydroxysteroid dehydrogenase, insulin-like growth factor (IGF-1) synergistically with LH increases gene expression, but do not stimulate steroidogenesis.

Ovarian steroidogenesis is always LH-dependent. As the follicle grows, the current cells express the P450c17 enzyme, which forms androgen from cholesterol. Granulosa cells do not have this enzyme and are dependent on the current cells in the production of estrogens from androgens. Unlike steroidogenesis - folliculogenesis depends on FSH. As the follicle grows and estrogen levels increase, the feedback mechanism comes into play - FSH production slows down, which in turn leads to a decrease in the aromatic activity of the follicle and, ultimately, to follicle atresia through apoptosis (programmed cell death).

The feedback mechanism of estrogens and FSH inhibits the development of follicles that started growing, but not the dominant follicle. The dominant follicle contains more FSH receptors that support the proliferation of granulosa cells and the aromatization of androgens in estrogens. In addition, the paracrine and autocrine pathway acts as an important coordinator for the development of the antral follicle.

An integral part of autocrine / paracrine regulator are peptides (inhibin, activin, follistatin), which are synthesized by granulosa cells in response to the action of FSH and enter the follicular fluid. Inhibin reduces FSH secretion; activin stimulates the release of FSH from the pituitary gland and enhances the action of FSH in the ovary; Follistatin suppresses FSH activity, possibly due to the binding of activin. After ovulation and development of the yellow body, inhibin is under the control of LH.

The growth and differentiation of ovarian cells is influenced by insulin-like growth factors (IGE). IGF-1 acts on granulosa cells, causing an increase in cyclic adenosine monophosphate (cAMP), progesterone, oxytocin, proteoglycan, and inhibin.

IGF-1 acts on teka cells, causing an increase in the production of androgens. Teka cells, in turn, produce tumor necrosis factor (TNF) and epidermal growth factor (EGF), which are also regulated by FSH.

EGF stimulates proliferation of granulosa cells. IGF-2 is the main factor of follicular fluid growth, it also detected IGF-1, TNF-a, TNF-3 and EGF.

Violation of paracrine and / or autocrine regulation of ovarian function seems to play a role in disturbances of ovulation processes and in the formation of polycystic ovaries.

As the antral follicle grows, the content of estrogens in the follicular fluid increases. At the peak of their increase on granulosa cells, receptors for LH appear, luteinization of granulosa cells occurs and progesterone production increases. Thus, during the preovulatory period, an increase in the production of estrogens causes the appearance of LH receptors, LH, in turn, causes luteinization of granulosa cells and progesterone production. The increase in progesterone reduces the level of estrogens, which, apparently, causes the second peak of FSH in the middle of the cycle.

It is believed that ovulation occurs 10-12 hours after the peak of LH and 24-36 hours after the peak of estradiol. It is believed that LH stimulates the reduction of the oocyte, the luteinization of granulosa cells, the synthesis of progesterone and prostaglandin in the follicle.

Progesterone enhances the activity of proteolytic enzymes, together with prostaglandin involved in rupturing the wall of the follicle. Progesterone induced FSH peak, allows the oocyte to exit from the follicle by converting plasminogen to a proteolytic enzyme-plasmin, provides a sufficient number of LH receptors for the normal development of the luteal phase.

Within 3 days after ovulation granulosa cells increase, characteristic vacuoles filled with pigment, lutein, appear in them. Teka-luteal cells differentiate from teki and stroma and become part of the yellow body. Very quickly, under the influence of angiogenesis factors, the development of capillaries penetrating the yellow body is progressing, and with the improvement of vascularization the production of progesterone and estrogens is increased. The activity of steroidogenesis and the life span of the yellow body are determined by the level of LH. The yellow body is not a homogeneous cellular entity. In addition to the 2 types of luteal cells, there are endothelial cells, macrophages, fibroblasts, etc. Large luteal cells produce peptides (relaxin, oxytocin) and are more active in steroidogenesis with greater aromatase activity and greater synthesis of progesterone than small cells.

The peak of progesterone is observed on the 8th day after the peak of LG. It was noted that progesterone and estradiol in the luteal phase are secreted sporadically in correlation with the pulse output of LH. With the formation of a yellow body, control over the production of inhibin passes from FSH to LH. Ingibin increases with the increase in estradiol to the peak of LH and continues to increase after the peak of LH, although the level of estrogens decreases. Although inhibin and estradiol are secreted by granulosa cells, they are regulated in different ways. The decrease in inhibin at the end of the luteal phase contributes to an increase in FSH for the next cycle.

The yellow body very quickly - on the 9-11 day after ovulation decreases.

The mechanism of degeneration is not clear and is not related to the lyuteolitic role of estrogens or to the receptor-linked mechanism, as seen in the endometrium. There is another explanation for the role of estrogens produced by the yellow body. It is known that for the synthesis of progesterone receptors in the endometrium, estrogens are required. Luteal phase estrogens are probably necessary for progesterone-related changes in the endometrium after ovulation. Inadequate development of the progesterone receptors, as a result of inadequate estrogen content, is probably an additional mechanism of infertility and early pregnancy loss, another form of inferiority of the luteal phase. It is believed that the life span of the yellow body is set at the time of ovulation. And it will certainly be regressed if the chorionic gonadotropin is not supported in connection with pregnancy. Thus, regression of the yellow body leads to a decrease in the levels of estradiol, progesterone and inhibin. Reduction inhibin removes its inhibitory effect on FSH; reduction of estradiol and progesterone allows very quickly to restore the secretion of GnRH and to remove the mechanism of feedback from the pituitary. Reduction of inhibin and estradiol, together with an increase in GnRH, leads to prevalence of FSH over LH. An increase in FSH leads to the growth of follicles with the subsequent choice of the dominant follicle, and a new cycle begins, in the event that a pregnancy does not occur. Steroid hormones play a leading role in reproductive biology and in general physiology. They determine the phenotype of a person, affect the cardiovascular system, the metabolism of bones, skin, the general well-being of the body and play a key role in pregnancy. The action of steroid hormones reflects the intracellular and genetic mechanisms that are necessary to transfer the extracellular signal to the nucleus of the cell to induce a physiological response.

Estrogens diffuse through the cell membrane and bind to receptors located in the nucleus of the cell. The receptor-steroid complex then binds to DNA. In target cells, these interactions lead to gene expression, the synthesis of proteins, to a specific function of cells and tissues.