Structural and functional characteristics of the ovarian cycle. Ovary. Ovarian cycle and its hormonal regulation. Intrauterine fetal growth

Oogenesis consists of the stages of reproduction, growth and maturation. The reproduction stage ends during the fetal period, after which new oogonia are not formed. Each ovary of a newborn girl contains about 2 million oocytes in the prophase of the first meiotic division as part of the primordial follicles. By the beginning of puberty, the total number of primordial follicles in both ovaries is estimated at 200-400 thousand. All other stages of oogenesis occur during the development of follicles during the ovarian cycle; during the entire reproductive period of a woman, only about 400-500 follicles mature (less than 2%).

The ability to fertilize in women, unlike men, changes cyclically, since the formation of mature eggs occurs irregularly in them. In contrast to the male body, in which millions of gametes are formed every day, in the female body only one or a few eggs mature, and then at a certain time.

ABOUT varial menstrual cycle- periodic changes in the body of a woman of reproductive age aimed at the possibility of conception. The duration of the menstrual cycle (normal) is about 28 (± 7 days). The beginning of the menstrual cycle is considered the first day of menstruation.

A regular menstrual cycle is ensured by hormones of the adenopituitary-hypothalamic system, which support the rhythmic secretion of follitropin and lutropin. Events that occur during the menstrual cycle involve the ovaries (ovarian cycle) and the uterus (uterine cycle.

Ovarian cycle. First half of the cycle - follicular(under the influence of FSH, some of the follicles develop), the second half - luteal(under the influence of LH, an endocrine gland is formed from the cells of the ovulated Graafian vesicle - the corpus luteum). Ovulation occurs approximately in the middle of the cycle. During ovulation, a second-order oocyte separates from the wall of the ruptured follicle, exits into the abdominal cavity and enters the fallopian tube.

In place of the burst follicle, following ovulation, a corpus luteum is formed, which develops from the walls of the emptied follicle. Follicular cells divide and become luteocytes (luteal cells).

Corpus luteum is a temporary gland that produces hormone progesterone. After a few days, it begins to dissolve and the cavity of the former follicle is filled with connective tissue. At the same time, the production of progesterone decreases and then stops. New follicles begin to develop in the ovaries, and the secretion of estrogen hormones increases again. The unfertilized egg remains in the uterus for several days and then dies. With the disappearance of the corpus luteum, the uterine mucosa undergoes reverse development. In humans and higher apes, its integrity is disrupted, resulting in bleeding - menstruation(from Latin menstrus - monthly) .

Uterine cycle. The uterine cycle is divided into three phases associated with certain structural and functional changes in the endometrium.

Menstrual phase characterized by rejection of the epithelial layer of the endometrium. Just before menstruation, the blood supply to this area decreases as a result of narrowing of the spiral arterioles in the uterine wall, caused by a drop in the level of progesterone in the blood after involution of the corpus luteum. Insufficient blood supply leads to the death of epithelial cells. Then the narrowing of the spiral arterioles is replaced by their expansion, and under the influence of increased blood flow, the endometrium is rejected, and its remains are excreted along with the blood in the form of menstrual flow.

Proliferative phase coincides with the follicular phase of the ovarian cycle and consists of rapid proliferation of endometrial cells, leading to its thickening under the control of estrogen secreted by the developing follicle.

Secretory phase provided by progesterone, secreted by the corpus luteum and stimulating the secretion of mucus by the tubular glands. Together with estrogens, progesterone prepares the endometrium for implantation of a fertilized egg.

If fertilization occurs, the embryo produces human chorionic gonadotropin(CG) to maintain the function of the corpus luteum of pregnancy and continue the synthesis of progesterone. If fertilization does not occur, progesterone synthesis stops and the endometrium sloughs off; approximately 5 days after this, menstruation occurs.

Hormonal regulation The ovarian and uterine cycles are carried out by the hypothalamus-pituitary-ovarian system. GnRH, released by hypothalamic neurons, stimulates the secretion of gonadotropins - follicle-stimulating hormone (FSH) and luteinizing hormone (LH). FSH induces follicular maturation. In women, only one of them matures at the same time (extremely rarely - two or more). The maturing follicle produces ever-increasing amounts of estradiol, which causes proliferation of the endometrium. Having reached a sufficiently high concentration, estradiol, through a positive feedback mechanism, increases the release of GnRH in the middle of the menstrual cycle and increases the sensitivity of the pituitary cells that secrete FSH and LH to it. The result is a peak in the release of these hormones in the middle of the cycle. LH causes ovulation and luteinization of granulosa cells of the follicle. The latter, under its influence, begin to secrete progesterone. Steroids, estradiol and progesterone act on the hypothalamus and pituitary gland through a negative feedback mechanism, suppressing the secretion of FSH and LH in the second half of the cycle. Both hormones also act on the higher parts of the central nervous system, so in animals sexual desire (libido) largely depends on the stage of the cycle. In addition, there are a number of cyclic changes in other body systems: cardiovascular system, respiratory, changes in water balance, in sensory systems and higher parts of the central nervous system, which is manifested in the dynamics of sensory sensitivity, psycho-emotional stress and mental performance.

Table of contents of the topic "Ejaculation (ejaculation). Reproductive function of the female body. Ovarian cycle. Menstrual cycle (uterine cycle). Female sexual intercourse.":
1. Ejaculation (ejaculation). Regulation of ejaculation. Seminal fluid.
2. Orgasm. The orgasmic stage of male sexual intercourse. Stage of resolution of male sexual intercourse. Refractory period.
3. Reproductive function of the female body. Female reproductive function. The stage of preparation of a woman’s body for fertilization of an egg.

5. Ovulation. Ovulatory phase of the ovulatory cycle.
6. Luteal phase of the ovulatory cycle. Corpus luteum phase. Yellow body. Functions of the corpus luteum. Menstrual corpus luteum. Corpus luteum of pregnancy.
7. Luteolysis of the corpus luteum. Lysis of the corpus luteum. Destruction of the corpus luteum.
8. Menstrual cycle (uterine cycle). Phases of the menstrual cycle. Menstrual phase. Proliferative phase of the menstrual cycle.
9. Secretory phase of the menstrual cycle. Menstrual bleeding.
10. Female sexual intercourse. Stages of female sexual intercourse. Sexual arousal in a woman. Excitement stage. Manifestations of the excitement stage.

Ovarian cycle consists of three physiological phases: follicular, ovulatory And luteal, or corpus luteum phases. Follicular phase The ovarian cycle begins in a woman from the moment menstrual bleeding begins. This phase varies in time from 9 to 23 days, but is relatively constant for each woman. Ovulatory phase lasts approximately 1-3 days and ends with ovulation. Rice. 16.9. Scheme of steroidogenesis in the cells of the female gonads. The efficiency of follicle development in the ovaries depends on the regulatory influence of adenohypophysis gonadotropins on them. Receptors on the membrane of the inner membrane cells - for lutropin (RLt) and on the membrane of granulosa cells - for follitropin (RFt), appear in the preantral and early antral stages of follicle development. The binding of hormones to lutropin and follitropin receptors stimulates the synthesis of steroid hormones in cells. Lutropin in thecal cells stimulates the conversion of acetate and cholesterol into androgens (70% of those circulating in the blood plasma). Under the influence of lutropin, thecal cells synthesize a small amount of estrogens. Estrogens and androgens diffuse in small quantities into granulosa cells and, under the influence of follitropin, these hormones are aromatized into estrogens. The main estrogens are estradiol-17B and estrone. The final phase of the ovarian cycle, luteal, during which the hormonal activity of the corpus luteum continues, lasts approximately 14 days.

Follicular phase

During each ovarian cycle starts slow follicle development, the number of which increases over the next two cycles. During this period, approximately 20 follicles reach a size of 2-4 mm and in the subsequent cycle, due to the appearance of follitropin receptors on the membrane of follicular cells, they begin to develop under the influence of this hormone. In about one week during the follicular phase, one of the follicles, on the membrane of which the density of follitropin receptors is higher than that of other follicles, reaches an average size of 11 mm and becomes dominant (secondary follicle). This is due to the fact that it synthesizes more estradiol-17B than other follicles. With a high density of follitropin receptors on the membrane of the dominant follicle, it retains the ability to synthesize estradiol-17B during a cyclic decrease in follitropin secretion in the woman’s adenohypophysis. Under these conditions, other follicles, which have a low density of follitropin receptors on their membrane, synthesize a small amount of estradiol-17B and undergo atresia. The function of follitropin in the development of a dominant follicle is as follows. We recommend watching this training video: Rice. 16.10. Dynamics of lutropin and follitropin content in blood plasma during the menstrual cycle. The successful development of ovulation during the short ovulatory phase depends on a sharp and rapidly passing peak in the secretion of lutropin and follitropin. Gonadotropin secretion peaks over approximately 15 hours, reaches a relatively constant level (the next 15 hours), and then decreases to baseline levels over the next 20 hours. This hormone binds to the membrane receptors of granulosa cells and stimulates the synthesis of aromatase in them, which converts testosterone into estradiol-17B. Testosterone is synthesized in the inner cells of the outer shell of the follicle (theca) and diffuses into granulosa cells, where the hormone is converted into estrogens (Fig. 16.9). The amount of androgens of follicular origin in a woman is approximately 70% of their total concentration in the blood plasma. Granulosa cells contain estrogen receptors, to which estradiol formed in them binds and stimulates the proliferation of these cells, increasing the size of the follicle. At the same time, estradiol-17B, through B-type estrogen receptors, activates the formation of new follitropin receptors in granulosa cells. Therefore, the more granulosa cells are formed in the follicle, the more androgens are aromatized into estrogens, which stimulate the granulosa cells to produce even more estradiol-17(3) (positive feedback mechanism). The increasing synthesis of estrogens in granulosa cells leads to an increase in the concentration of female sex hormones in blood plasma. Estrogens, together with follitropin, stimulate the formation of receptors for lutropin on the membrane of granulosa cells, which is the main regulator of the next stage of development of the antral follicle (tertiary follicle). Lutropin binds to receptors on the membrane of granulosa cells and cells of the inner layer of the outer membrane (theca) and stimulates accumulation of lipids, yellow pigment in them, as well as a pre-ovulatory increase in the formation of progesterone, which initiates ovulation.At the end of the follicular phase, under the influence of increasing secretion of estrogens in the follicle and an increase in the blood plasma concentration of the ovarian cytokine inhibin, the secretion of follitropin in the adenohypophysis is inhibited by a negative mechanism feedback. In this case, a high level of estrogen in the blood plasma causes inhibition of the secretion of gonadoliberin in the hypothalamus and follitropin in the pituitary gland. On the contrary, these same hormones (estrogens and inhibin), through a positive feedback mechanism, stimulate a sharp increase in the concentration of lutropin in the blood plasma 24-36 hours before the onset of ovulation (Fig. 16.10). Normal ovulation during the short ovulatory phase depends on the release, in the form of a quickly passing peak in the concentration of gonadotropins in the blood plasma, primarily lutropin.

Menstrual cycle- cyclical changes in a woman’s body, the external manifestation of which is menstruation.

Cyclic changes in the ovaries - the ovarian cycle - are divided into follicular and luteal phases, and changes in the endometrium - the uterine cycle - into proliferative and secretory phases. As a result of the rejection of the functional layer of the endometrium, menstruation occurs. Menarche is the first menstruation. It is usually observed at 10-12 years of age, while a regular cycle is usually established after 1-1.5 years. The average cycle is 28 days, normal is from 21 to 35 days. The first day of menstruation corresponds to the first day of the menstrual cycle. The duration of menstruation is 2-7 days (on average 4-5 days), blood loss is from 50 to 150 ml (on average 70-100 ml).

The menstrual cycle is determined by the conjugate work of five links of the neurohumoral chain (cerebral cortex, hypothalamus, pituitary gland, ovaries, uterus).

The main secretion products of the hypothalamus are pituitary releasing factors. Gonadotropin releasing hormone (GnRH) controls the secretion of pituitary gonadotropins, luteinizing hormones (LH) and follicle-stimulating hormones (FSH) (Fig. 4).

GnRH is the only hormone that regulates the pulsatile secretion of two pituitary hormones. Chronic infusion of GnRH does not stimulate the secretion of gonadotropins. The pulsatile mode of GnRH secretion (Fig. 5) is necessary due to the very short period of RG puluralysis - about 2-4 minutes. During the menstrual cycle, the frequency and amplitude of GnRH pulsations change: in the follicular phase they are high, and in the luteal phase they decrease.

Rice. 4. Regulation of the menstrual cycle

Rice. 5. Pattern of GnRH secretion

The end of each menstrual cycle and the beginning of the next are characterized by low levels of sex steroids: progesterone and estrogens.

With the cessation of corpus luteum function, the production of FSH and LH increases. Granulosa cells interact with FSH, and cells of the inner thecal layer interact with LH. Every menstrual cycle(Fig. 6) from 3 to 30 primordial follicles, under the influence of FSH, enter the growth phase and secrete estrogens, the level of which progressively increases during the 1st - follicular phase menstrual cycle.

During the growth of secondary follicles (by the 8th day of the menstrual cycle), dominant follicle turning into tertiary follicle(preovulatory, hereinafter graphs bubble, up to 2-3 cm in diameter).

Estrogen synthesis is achieved in two ways. The first pathway involves the enzymatic aromatization of androgens into estrogens by granulosa cells. The second pathway is associated with the synthesis of estrogens in thecal cells in the late stages of the antral phase. Thus, in the middle of the follicular phase, the level of follicular estrogens and androgens increases, which is accompanied by a decrease in FSH concentration (negative feedback).

At the same time, estrogens stimulate the secretion of LH throughout the follicular period.

FSH stimulates:

Growth phase of primordial follicles;

Transport of fluid into the follicle cavity;

Expression of receptors for LH and prolactic acid on granulosa cells;

Aromatase activity. LH stimulates:

Production by follicular cells of low molecular weight proteins that neutralize the factor that suppresses meiosis;

Meiotic division of the oocyte and transition to the 2nd order stage - haploid set;

Synthesis of androgens - androstenedione and testosterone - in cells theca;

Progesterone synthesis (luteinization) in follicular cells;

Synthesis of prostaglandins in follicular cells;

Ovulation induction.

In the preovulatory phase, on granulosa cells of the follicle, FSH induces the development of receptors for LH and prolactin. Thus, at the end of the preovulatory phase, the content of FSH and LH increases, and follicular cells become insensitive to the effects of estrogens and androgens. High concentrations of estrogen stimulate the trigger release of LH and rupture of the wall of the Graafian vesicle (tertiary follicle) - i.e. ovulation, occurring 10-12 hours after the peak of LH levels. Then the egg is released into the abdominal cavity, and begins luteal phase of the cycle.

Estrogens:

Stimulate the proliferation of follicular cells;

Stimulate the expression of FSH receptors;

They take part (together with FSH) in the formation of LH receptors in follicular cells;

Increase LH secretion; with a high estrogen content, GnRH stimulates cells that synthesize LH;

Suppress the secretion of FSH; when estrogen levels are low, GnRH stimulates cells that synthesize FSH.

Androgens:

Inhibit the expression of FSH receptors on granulosa cells;

Inhibits aromatase activity.

The resulting capillaries quickly grow into the follicle cavity, granulosa cells undergo luteinization under the influence of LH, which leads to the formation of the corpus luteum.

Estrogen levels begin to decline from the end of the preovulatory phase against the background of high concentrations of FSH and LH, continue to fall during the early luteal phase and rise again as a result of secretion of the corpus luteum.

Corpus luteum(corpus luteum) is a transient endocrine gland that functions for 8-14 days, regardless of the duration of the menstrual cycle, and synthesizes progesterone, estrogens (mainly 17b-estradiol) and prolactin. Progesterone levels gradually increase after ovulation and peak 8-9 days after ovulation, which is approximately the time of implantation. The thermogenic effect of progesterone leads to an increase in body temperature by at least 0.33 ° C (the effect lasts until the end of the luteal phase).

Progesterone:

Prepares the endometrium for nidation;

Relaxes myometrial fibers;

Has a natriuretic effect, stimulating the secretion of aldosterone;

Placental progesterone is metabolized in the fetal adrenal cortex and testes as a precursor to corticosteroids and testosterone, respectively.

Thus, the luteal phase is characterized by increased concentrations of progesterone and prolactin and low levels of FSH and LH.

As the function of the corpus luteum regresses, the concentrations of sex steroids decrease and a new menstrual cycle begins.

In addition to the listed hormones, the corpus luteum and subsequently the placenta produce relaxin. It inhibits the contractile activity of the myometrium by activating the action of progesterone and increasing the level of cAMP both in the smooth muscle cells of the myometrium and in the chondrocytes of the symphysis pubis, causing its softening.

White body- connective tissue scar in place of the completed function and degenerated corpus luteum.

OVARIAL CYCLE

The number of oogonia in a female embryo by the middle of intrauterine development reaches 5-7 million, however, a significant part of the oocytes undergoes atresia (Fig. 7), associated with low production of gonadotropic hormones. A newborn girl’s ovaries already contain 1-2 million oocytes; by the period of puberty, there are from 100 to 400 thousand of them. During the reproductive period, 98% of primordial follicles die, about 2% reach the stage of primary and secondary follicles, but no more than 400-500 ovulate. All follicles that have begun to develop but have not reached the ovulation stage undergo atresia.

Thus, the lifespan of an oocyte can reach 40-50 years. This is why the risk of fetal gene defects increases significantly with maternal age.

Rice. 7. Pattern of GnRH secretion

FOLLICLE STRUCTURE

Primordial follicle covered by a single layer of follicular cells (granulosa) and surrounded by a basement membrane. The granulosa cells surrounding the oocyte (“corona radiata”) secrete a glycoprotein substrate, which forms a transparent zone - zona pellucida- between the oocyte and granulosa cells. On the surface of the zona pellucida there are species-specific receptors for interaction only with allogeneic spermatozoa; penetration of the zone by one sperm leads to the development of a “zonal reaction” that prevents polyspermy.

The cells of the ovarian stroma form a layer of spindle cells - theca. Androgens, which ensure the development of follicles, are produced exclusively by thecal cells. As a result of proliferation, the latter are divided into two layers: the inner one, which has a glandular structure, and the outer one - connective tissue. Follicular fluid accumulates between them, containing serum transudate and mucopolysaccharide secretion of granulosa cells. The accumulation of fluid gives the follicle the appearance of a vesicle and such a follicle is called

is secondary or antral (Fig. 8). The oocyte located in it has not yet undergone the second meiotic division.

The primordial follicle is covered by a single layer of follicular cells (granulosa) and surrounded by a basement membrane

Rice. 8. Follicle growth

Rice. 9. Tertiary follicle (“Graafian vesicle”)

The development of the oocyte continues until fertilization, and the transformation of a 1st order oocyte into a 2nd order oocyte, which already has a haploid set of chromosomes, occurs either immediately before ovulation or in the fallopian tube.

During each ovarian cycle, 15-20 follicles develop in the ovaries. Some of them reach large sizes (up to 8 mm) by the middle of the cycle, but only one follicle becomes a mature tertiary follicle with a diameter of 2-3 cm (“Graafian vesicle”, Fig. 9).

UTERINE CYCLE

Changes in hormonal levels directly affect the condition of the endometrium, mucous membrane of the fallopian tubes, cervical canal and vagina. The uterine mucosa undergoes cyclical changes (proliferative, secretory and menstrual phases). The endometrium is divided into functional (disappearing during menstruation) and basal (preserving during menstruation) layers.

Proliferative phase- the first half of the cycle - lasts from the first day of menstruation until the moment of ovulation. It is characterized by regeneration of the functional layer due to the migration and proliferation of epithelial cells of the glands of the basal layer to the surface under the influence of estrogens (mainly estradiol). In the endometrium, new uterine glands form and spiral arteries grow from the basal layer. The duration of the phase may vary. Basal body temperature is normal.

Secretory phase- second half - lasts from ovulation to the beginning of menstruation. Epithelial cells stop dividing and hypertrophy. The uterine glands expand, and glandular cells actively secrete glycogen, glycoproteins, lipids and mucin. In the superficial parts of the functional layer, the number of connective tissue cells increases, around which collagen and reticular fibers are formed. Spiral arteries become more convoluted, approaching the surface of the mucous membrane. If implantation of the fertilized egg has not occurred, a decrease in the content of ovarian steroid hormones leads to twisting, sclerosis and a decrease in the lumen of the spiral arteries supplying the upper two-thirds of the functional layer of the endometrium. As a result, there is a deterioration in blood flow in the functional layer, ischemia and rejection, i.e. bleeding.

Menstrual phase- rejection of the functional layer of the endometrium, lasts 3-7 days.

In order to determine the time of ovulation, various methods of functional diagnostics of the phases of the menstrual cycle are used. The following parameters are defined.

1. Basal temperature. It is associated with the thermogenic effect of progesterone (Fig. 10).

Cycle day 1 23456789 1010 11 12 13 14 15 16 17 1819 20 22 23 24 25 2627 2829

Rice. 10. Basal (rectal) temperature

2. Extensibility of cervical mucus. Under the influence of estrogens, the extensibility of mucus significantly increases. Reaches maximum values ​​during ovulation (Fig. 11)

3. The effect of arborization of cervical mucus (the “fern” phenomenon). This phenomenon is most pronounced during the period of ovulation due to

a high concentration of sodium salts that precipitate into crystals (a symptom of crystallization), externally resembling a surface in the form of a tree or fern (Fig. 12).

4. Karyopyknotic index - KPI (using microscopic analysis of a vaginal smear).

Rice. eleven. The degree of extensibility of cervical mucus

Rice. 12. The "fern" phenomenon

CPI is the ratio of keratinized cells with pyknotic (dotted) nuclei to all cells of the vaginal epithelium in the smear (Fig. 13, see inset). The highest CPI value corresponds to the ovulation period - 70-80%, on the remaining days of the menstrual cycle - up to 30-40%.

Embryology- the science of the embryo, the laws of its development. Medical embryology studies the patterns of development of the human embryo, the structural, metabolic and functional features of the placental barrier (mother-placenta-fetus system), the causes of deformities and other deviations from the norm, as well as the mechanisms of regulation of embryogenesis.

The concept of embryogenesis includes the period from the moment of fertilization to birth (for viviparous animals), hatching from eggs (for oviparous animals), and the end of metamorphosis (for animals with the larval stage of development).

FERTILIZATION

Transport of gametes. In humans, the normal volume of ejaculate is about 3 ml; it contains an average of 350 million sperm. To ensure fertilization, the total number of sperm must be at least 150 million, and their concentration in 1 ml must be at least 60 million. Due to high mobility, sperm under optimal conditions can reach the uterine cavity in 30 minutes - 1 hour, and in 1.5-2 h located in the distal (ampullary) part of the fallopian tube, where fertilization occurs. Sperm retain fertilizing ability for up to 2 days.

The first-order oocyte released from the ovary during ovulation has a diameter of about 130 microns and is surrounded by a dense zona pellucida, or membrane, and a crown of follicular cells, the number of which reaches 3-4 thousand. It is picked up by the fimbriae of the fallopian tube (oviduct) and moves along it. This is where the maturation of the germ cell ends. In this case, as a result of the second division, a second-order oocyte (egg) is formed, which loses its centrioles and thereby the ability to divide. The nucleus of a human egg contains 23 chromosomes; one of them is the sex X chromosome.

The human egg usually uses up its reserve of nutrients within 12-24 hours after ovulation, and then dies if it is not fertilized.

Fertilization occurs in the ampullary part of the oviduct. Optimal conditions for the interaction of sperm with the egg

usually created within 12 hours after ovulation. During insemination, numerous sperm approach the egg and come into contact with its membrane. The egg begins to perform rotational movements around its axis at a speed of 4 rotations per minute. These movements are caused by the beating of sperm flagella and last about 12 hours. During the interaction of male and female germ cells, a number of changes occur in them. Sperm are characterized by the phenomena of capacitation and acrosomal reaction. Capacitation is the process of activation of sperm in the fallopian tube under the influence of the mucous secretion of glandular cells. Progesterone activates the secretion of glandular cells. After capacitation, an acrosomal reaction follows, during which the enzymes hyaluronidase and trypsin are released from the sperm. Hyaluronidase breaks down hyaluronic acid contained in the zona pellucida. Trypsin breaks down the proteins of the cytolemma of the egg and corona radiata cells. As a result, the cells of the corona radiata dissociate and the zona pellucida dissolves.

In the egg, the cytolemma in the area of ​​attachment of the sperm forms a lifting tubercle, into which one sperm enters, and a dense membrane appears - the fertilization membrane, which prevents the entry of other sperm and the phenomenon of polyspermy. The nuclei of the female and male germ cells turn into pronuclei, move closer together, and the synkaryon stage begins. Arises zygote, and by the end of the 1st day after fertilization begins splitting up.

The sex of the child depends on the sex chromosomes of the father. Due to the greater sensitivity of male embryos to the damaging effects of various factors, the number of newborn boys is less than that of girls: for every 100 boys, 105 girls are born.

The movement of the fertilized egg is ensured by peristaltic contractions of the muscles of the tube and the flickering of the cilia of the epithelium. The embryo is nourished by small reserves of yolk in the egg and, possibly, the contents of the fallopian tube.

Transport of the embryo to the uterus occurs in an immunosuppressive environment, in the formation of which sperm, blastocyst fluid, A 2-uterine protein (begins to be produced by the glandular epithelium of the endometrium in the coming days after ovulation) and early pregnancy factor (EGF), first described by H. Morton in 1974. EGF is produced by the egg 46-48 hours after

le fertilization and is one of the first indicators of pregnancy and the earliest immunosuppressive agent that prevents blastocyst rejection. Immunological protection factors:

A 2 - endometrial gland protein;

Egg early pregnancy factor;

Syncytiotrophoblast immunoblocking proteins;

HCG and placental lactogen (PL);

Placental fibrinoid lycoproteins;

Proteolytic properties of trophoblast.

Human embryo fragmentation begins by the end of the 1st day and continues for 3-4 days after fertilization (as the embryo moves towards the uterus). The fragmentation of the human zygote is complete, uneven, asynchronous. During the first day it occurs slowly. The first division is completed after 30 hours; in this case, the cleavage furrow passes along the meridian and two blastomeres are formed. The two blastomere stage is followed by the four blastomere stage. After 40 hours, four cells are formed (Fig. 14, see inset).

From the very first divisions, two types of blastomeres are formed: “dark” and “light”. “Light” blastomeres fragment faster and are located in one layer around the “dark” ones, which end up in the middle of the embryo. From the surface “light” blastomeres, a trophoblast subsequently arises, connecting the embryo with the maternal organism and providing it with nutrition. The internal “dark” blastomeres form the embryoblast - the body of the embryo and all other extra-embryonic organs, except the trophoblast, are formed from it. By the time the blastocyst enters the uterus, it increases in size due to an increase in the number of blastomeres and fluid volume due to increased absorption of uterine gland secretions by the trophoblast and active production of fluid by the trophoblast itself.

In the trophoblast, the number of lysosomes increases, in which enzymes accumulate that provide lysis of uterine tissue and thereby facilitate the introduction of the embryo into the thickness of the uterine mucosa, i.e. nidation. Implantation (nidation) begins on the 7th day after fertilization and lasts about 40 hours (Fig. 15, see inset). In this case, the blastocyst is completely surrounded by endometrial tissue - the decidua.

The trophoblast layer soon differentiates into the outer layer - the syncytiotrophoblast, which is constantly replenished with nuclei and cytoplasm due to the underlying inner layer of cytotrophoblast (Langhans layer), since nuclear division is observed only in the cytotrophoblast. The third derivative of the trophoblast is non-proliferative and is a mononuclear cell type that was originally designated "X cells" and is also known as the "intermediate trophoblast". This is the main type of cells that make up the placental platform and, together with the cells of the decidua, penetrate into the maternal spiral arteries, and also form the bulk of the cells of the placental septa. X cells are the main source of human placental lactogen (HPL - human placental lactogen) and large amounts of essential pregnancy protein (MBP - major basic protein)

During the first 2 weeks, the trophoblast consumes the breakdown products of maternal tissues (histiotrophic type of nutrition). Then the syncytiotrophoblast, growing in the form of villi and producing proteolytic enzymes, penetrates the uterus, destroys the maternal decidual vessels, thereby allowing the mother’s blood to pour into uneven lacunae - which are the future “intervillous space”. Thus, the trophoblast comes into direct contact with the blood of the maternal vessels and the embryo begins to receive nutrition directly from the maternal blood (hematotrophic type of nutrition). Full blood circulation in the fetus is established approximately in the 5th week after fertilization.

After implantation is completed, a very important period of organogenesis and placentation begins in the development of the embryo. From the 20th to 21st days, the body of the embryo separates from the extraembryonic organs and the final formation of axial primordia occurs. Organogenesis is completed by the 12-16th week of intrauterine life.

The periods of antenatal development are shown in Fig. 16.

The embryonic mass differentiates, the germ layers are formed: 1) ectoderm; 2) mesoderm; 3) endoderm. They are also differentiated (Fig. 17, see inset).

The neural tube is formed from the ectoderm. The closure of the neural tube begins in the cervical region, then spreads posteriorly and cranially, where the medullary vesicles form. Approximately on the 25th day, the neural tube is completely closed, and from the external environment

Rice. 16. Periods of antenatal development

Only two non-closed openings are communicated with each other at the anterior and posterior ends - the anterior and posterior neuropores. After another 5-6 days, both neuropores are overgrown. When the side walls of the neural folds close and the neural tube forms, the so-called neural crest appears. Neural crest cells are capable of migration. In the trunk, migrating cells form the parasympathetic and sympathetic ganglia and the adrenal medulla. Some cells remain in the neural crest region, they are segmented and give rise to the spinal ganglia.

Differentiation mesoderm begins on the 20th day of embryogenesis.

Mesoderm cells rush to the inner surface of the blastocyst cavity and differentiate into the connective tissue of the chorion and villi. The place where these cells leave the embryo becomes the umbilical cord, into which the allantoic vessels of the future placenta grow.

Changes in the embryo itself are expressed in the fact that the dorsal sections of the mesodermal sheets are divided into dense segments lying on the sides of the notochord - somites. The process of formation of segments, or somites, begins in the head part of the embryo and spreads in the caudal direction. And if on the 22nd day of development the embryo has 7 pairs of segments, then on the 35th day there are 44 pairs. In the process of mesoderm differentiation, a nephrogenic rudiment and embryonic

The first rudiment of connective tissue is mesenchyme. Ecto- and endodermal cells partially participate in the formation of mesenchyme.

Endoderm forms a cavity - the primary gut, the future digestive tube, which develops through the stage of formation of the yolk sac. The separation of intestinal endoderm begins with the appearance of the trunk fold, which, going deeper, separates the embryonic endoderm - the primary gut - from the extraembryonic endoderm - the yolk sac. At the beginning of the 4th week, an ectodermal invagination is formed at the anterior end of the embryo - the oral fossa. Deepening, the fossa reaches the anterior end of the intestine and, after breaking through the membrane separating them, it turns into the oral opening of the unborn child.

The yolk sac and the digestive tube remain connected for some time through the omphalomesenteric duct (yolk stalk), ending in a potential Meckel's diverticulum. The yolk stalk, like the yolk sac, subsequently atrophies.

Thus, the yolk sac, formed by the extraembryonic endoderm and extraembryonic mesoderm, takes an active part in the nutrition and respiration of the human embryo for a very short time. The main role of the yolk sac is hematopoietic. As a hematopoietic organ, it functions until the 7-8th week, and then undergoes reverse development. In the wall of the yolk sac, primary germ cells - gonoblasts - are formed, migrating from it with the blood into the rudiments of the gonads.

In the posterior part of the embryo, the resulting intestine also includes that portion of the endoderm from which the endodermal outgrowth of the allantois arises.

The allantois is a small finger-shaped process of the endoderm that grows into the amniotic stalk. In humans, the allantois is not very developed, but its importance in ensuring nutrition and respiration of the embryo is still great, since vessels grow along it towards the chorion, the final branches of which lie in the stroma of the villi. At the 2nd month of embryogenesis, the allantois is reduced.

In Fig. 18 (see inset) shows what an embryo looks like at 4-5 weeks.

During the periods of organogenesis (Fig. 19) and placentation, as a result of the pathogenic action of environmental factors in the embryo and fetus, those organs and systems that are in this state are primarily affected.

time in the process of differentiation. For various embryonic organ anlages, critical periods do not coincide in time with each other. Therefore, the action of a damaging factor usually causes deformities of various organs and systems. The most sensitive phase of development is the first 3-6 weeks of ontogenesis (the second critical period of development).

Rice. 19. Periods of organogenesis

INTRAuterine GROWTH OF THE FETAL

The dynamics of fetal growth in the uterus is ensured by the interaction of the genetic potential of each individual fetus and the intrauterine environment, which is primarily associated with the function of the placenta and maternal homeostasis. The dynamics of fetal growth during physiological pregnancy corresponds to gestational age (Table 1).

Table 1

Dynamics of fetal growth

After 27 weeks of pregnancy, the dynamics of growth are influenced by the sex of the fetus (Table 2).

Table 2a

Weeks of gestation	Mass centiles for boys, g (A.V. Mazurin, I.M. Vorontsov, 2000)

Table 2b

Dynamics of fetal growth depending on gender

Weeks of gestation	Girls' mass centiles, g (A.V. Mazurin, I.M. Vorontsov, 2000)

The discrepancy between the size of the fetus and the actual period of pregnancy is defined by the concept of “intrauterine growth retardation” (IUGR) of the fetus. The international criterion for IUGR is fetal weight and/or height that is less than normal for gestational age (10th centile and below). IUGR syndrome is one of the clinical manifestations of placental insufficiency.

Placenta- an extra-embryonic organ through which a connection between the embryo and the mother’s body is established. The human placenta belongs to the type of discoidal hemochorial villous placenta. The formation of the placenta begins at the 3rd week, when vessels begin to grow into the secondary (epitheliomesenchymal) villi, forming tertiary villi, and ends at 14-16 weeks of pregnancy.

The placenta is divided into the embryonic, or fetal, part and the maternal, or uterine part.

The fetal part is represented by a branched chorion and the amniotic membrane attached to it, and the maternal part is represented by a modified basal part of the endometrium.

The embryonic, or fetal, part of the placenta by the end of the 3rd month is represented by a branching chorionic plate, consisting of fibrous (collagen) connective tissue covered with cyto- and syncytiotrophoblast. The branching villi of the chorion (stem, or anchor, villi) are well developed only on the side facing

myometrium. Here they pass through the entire thickness of the placenta and with their apices are immersed in the basal part of the destroyed endometrium.

The structural and functional unit of the formed placenta is the cotyledon, formed by the stem villi and its secondary and tertiary branches. The total number of cotyledons in the placenta reaches 200.

The maternal part of the placenta is represented by the basal plate and connective tissue septa that separate the cotyledons from each other, as well as lacunae filled with maternal blood.

On the surface of the basal plate, facing the chorionic villi, there is an amorphous substance - Rohr fibrinoid. Trophoblastic cells of the basal lamina, together with fibrinoid, play a significant role in ensuring immunological homeostasis in the mother-fetus system.

The blood in the lacunae is continuously renewed. It comes from the uterine arteries, which enter here from the muscular lining of the uterus. These arteries run along the placental septa and open into lacunae. Maternal blood flows from the placenta through veins originating from the lacunae.

The blood of the mother and the blood of the fetus circulate through independent vascular systems and do not mix with each other. The hemochorionic barrier separating both blood flows consists of the endothelium of the fetal vessels, the surrounding connective tissue vessels, the epithelium of the chorionic villi (cytotrophoblast, syncytiotrophoblast), and in addition, fibrinoid, which in some places covers the villi from the outside.

The placenta performs trophic, excretory (for the fetus), endocrine (produces hCG, progesterone, PL, estrogens, etc.), protective (including immunological protection) functions.

HCG value

Stimulates the production of progesterone by the corpus luteum.

Stimulates Leydig cells of male fetuses and testosterone production.

Determines the development of male genital organs.

It is an early marker of pregnancy.

It is a criterion for assessing the effectiveness of treatment of trophoblastic tumors, as well as an ovulation inducer due to its biological similarity to PH

PL properties

Participates in immunological defense - inhibits maternal lymphocytes.

Stimulates lipolysis and increases the concentration of free fatty acids.

Inhibits maternal gluconeogenesis.

Increases plasma insulin levels.

Stimulates the synthesis of proteins and amino acids due to the insulinogenic effect.

The concentration of PL depends on the weight of the placenta.

Amniotic membrane. It is avascular and forms the innermost wall of the fruit receptacle. Its main function is the production of amniotic fluid, which provides an environment for the developing organism and protects it from mechanical damage. The epithelium of the amnion, facing its cavity, secretes amniotic fluid and also takes part in their reabsorption. In this case, in the epithelium of the amnion covering the placental disc, predominantly secretion takes place, and in the epithelium of the extraplacental amnion, predominantly resorption of amniotic fluid occurs. Amniotic fluid creates the aqueous environment necessary for the development of the embryo, maintaining the necessary composition and concentration of salts in the amniotic fluid until the end of pregnancy. The amnion also performs a protective function, preventing harmful agents from entering the fetus.

The amnion is loosely connected to the chorion, in which the fetal vessels are located. Its attachment to the chorion occurs around the 12th week of pregnancy; Before this, there is a space filled with fluid between the amnion and chorion. In addition, the amnion often moves during pregnancy and can even detach long before birth. It also sometimes forms cords, which, if they come into contact with the fetus, can cause prenatal amputations and other deformities. Since the amnion is connected to the umbilical cord and is tightly attached to it, the remains of the cords are most often found at the site of attachment of the umbilical cord.

Umbilical cord

The umbilical cord is formed mainly from mesenchyme located in the amniotic stalk and vitelline stalk. The allantois and the vessels growing along it also take part in the formation of the cord. On the surface, all these formations are surrounded by the amniotic membrane. The yolk stalk and allantois are quickly reduced, and only their remains are found in the umbilical cord of the newborn.

The formed umbilical cord is an elastic connective tissue formation in which two umbilical arteries and an umbilical vein pass. It is formed by typical gelatinous (mucous) tissue, which contains a huge amount of hyaluronic acid. It is this tissue, called Wharton's jelly, that provides the turgor and elasticity of the cord. It protects the umbilical vessels from compression, thereby ensuring a continuous supply of nutrients and oxygen to the embryo.

Normally, the umbilical cord is attached to the placenta disc (central attachment), in 7% there is a marginal attachment (battledore) and in 1% - on the membranes (mechanical attachment). Abnormal attachments are more common in multiple pregnancies. Implantation of the placenta is not associated with fetal anomalies, but can be dangerous due to the increased incidence of vascular thrombosis and the possibility of bleeding from vessels ruptured during childbirth.

The length of the umbilical cord is largely determined by the motor activity of the fetus. Thus, a short umbilical cord often indicates its immobility due to neuromuscular pathology or amniotic fusions. On the contrary, a long umbilical cord is sometimes the result of increased motor activity of the fetus.

A single umbilical cord artery occurs in more than 1% of cases, more often in multiple pregnancies. About half of these newborns have congenital anomalies, some of which should be actively diagnosed, and other perinatal problems. A single umbilical cord artery, however, can be present in a completely normal newborn; then this finding only signals the need for caution regarding the presence of pathology in this newborn.

Despite the fact that the body of the mother and fetus are genetically foreign in the composition of proteins, an immunological conflict usually does not occur.

walks. This is ensured by a number of factors; Of these, the following are especially important:

1 - proteins synthesized by syncytiotrophoblast that inhibit the immune response of the maternal body;

2 - hCG and PL, located in high concentrations on the surface of the syncytiotrophoblast, taking part in the inhibition of maternal lymphocytes;

3 - immunomasking effect of glycoproteins of placental fibrinoid, charged, like the lymphocytes of washing blood, negatively;

4 - proteolytic properties of the trophoblast, which also contribute to the inactivation of foreign proteins;

5 - amniotic fluid with antibodies that block antigens A and B (contained in the blood of a pregnant woman) and prevent them from entering the blood of the fetus in the event of an incompatible pregnancy.

In the process of formation of the mother-fetus system, there are a number of critical periods that are most significant for establishing interaction between the two systems and for creating optimal conditions for fetal development.

In human ontogenesis, several critical periods of development can be distinguished: in progenesis, embryogenesis and postnatal life. These include:

1) development of germ cells - oogenesis and spermatogenesis;

2) fertilization;

3) implantation (7-8 days of embryogenesis);

4) development of axial organ rudiments and formation of the placenta (3-8th week of development);

5) stage of increased brain growth (15-20th week);

6) formation of the main functional systems of the body and differentiation of the reproductive apparatus (20-24th week);

7) birth;

8) neonatal period (up to 1 year);

9) puberty (11-16 years).

Menstrual cycle (ovarian and uterine).

The ovarian cycle consists of two phases- follicular and luteal, which are separated by ovulation and menstruation.The duration of the ovarian (menstrual) cycle normally varies from 21 to 35 days.

INfollicular phase under the influence of FSH, the growth and development of one or more primordial follicles is stimulated, as well as the differentiation and proliferation of granulosa cells. FSH also stimulates the processes of growth and development of primary follicles, the production of estrogens by follicular epithelial cells. Estradiol, in turn, increases the sensitivity of granulosa cells to the action of FSH. Along with estrogens, small amounts of progesterone are secreted. Of the many follicles that begin to grow, only 1 will reach final maturity, less often 2-3. The preovulatory release of gonadotropins determines the process of ovulation itself. The volume of the follicle increases rapidly in parallel with the thinning of the follicle wall. The significant increase in estrogen levels observed within 2-3 days before ovulation is due to the death of a large number of mature follicles with the release of follicular fluid. High concentrations of estrogen inhibit the secretion of FSH by the pituitary gland through a negative feedback mechanism. The ovulatory surge of LH and, to a lesser extent, FSH is associated with the existence of a positive feedback mechanism of ultra-high concentrations of estrogen and LH levels, as well as with a sharp drop in estradiol levels during the 24 hours preceding ovulation.

Ovulation of the egg occurs only in the presence of LH or human chorionic gonadotropin. Moreover, FSH and LH act as synergists during the development of the follicle, and at this time the theca cells actively secrete estrogens.

After ovulation, there is a sharp decrease in the levels of LH and FSH in the blood serum. From the 12th day of the second phase of the cycle, a 2-3-day increase in the level of FSH in the blood is observed, which initiates the maturation of a new follicle, while the concentration of LH throughout the second phase of the cycle tends to decrease.

The cavity of the ovulated follicle collapses, and its walls gather into folds. Due to the rupture of blood vessels at the time of ovulation, hemorrhage occurs in the cavity of the postovulatory follicle. A connective tissue scar appears in the center of the future corpus luteum - stigma

The ovulatory surge of LH and the subsequent maintenance of high levels of the hormone for 5-7 days activates the process of proliferation and glandular metamorphosis of granular zone cells with the formation of luteal cells, i.e. comes luteal phase ovarian cycle.

The epithelial cells of the granular layer of the follicle multiply intensively and, accumulating lipochromes, turn into luteal cells; the membrane itself is abundantly vascularized. The vascularization stage is characterized by the rapid proliferation of epithelial granulosa cells and intensive ingrowth of capillaries between them. The vessels penetrate into the cavity of the postovulatory follicle from the side thecae internae into the luteal tissue in a radial direction. Each cell of the corpus luteum is richly supplied with capillaries. Connective tissue and blood vessels, reaching the central cavity, fill it with blood, envelop the latter, limiting it from the layer of luteal cells. The corpus luteum has one of the highest levels of blood flow in the human body. The formation of this unique network of blood vessels ends within 3-4 days after ovulation and coincides with the heyday of the function of the corpus luteum (Bagavandoss P., 1991).

Angiogenesis consists of three phases: fragmentation of the existing basement membrane, migration of endothelial cells and their proliferation in response to a mitogenic stimulus. Angiogenic activity is controlled by major growth factors: fibroblast growth factor (FGF), epidermal growth factor (EGF), platelet-derived growth factor (PLGF), insulin-like growth factor-1 (IGF-1), as well as cytokines such as necrotic factor tumor (TNF) and interleukins (IL-1; IL-6) (Bagavandoss P., 1991).

From this moment on, the corpus luteum begins to produce significant amounts of progesterone. Progesterone temporarily inactivates the positive feedback mechanism, and the secretion of gonadotropins is controlled only by the negative influence of estradiol. This leads to a decrease in the level of gonadotropins in the middle of the corpus luteum phase to minimal values ​​(Erickson G.F., 2000).

Progesterone, synthesized by the cells of the corpus luteum, inhibits the growth and development of new follicles, and also participates in the preparation of the endometrium for the implantation of a fertilized egg, reduces the excitability of the myometrium, suppresses the effect of estrogens on the endometrium in the secretory phase of the cycle, stimulates the development of decidual tissue and the growth of alveoli in the mammary glands. The plateau of serum progesterone concentration corresponds to the plateau of rectal (basal) temperature (37.2-37.5 ° C), which underlies one of the methods for diagnosing ovulation that has occurred and is a criterion for assessing the usefulness of the luteal phase. The basis for the increase in basal temperature there is a decrease in peripheral blood flow under the influence of progesterone, which reduces heat loss. An increase in its content in the blood coincides with an increase in basal body temperature, which is an indicator of ovulation.

Progesterone, being an antagonist of estrogen, limits their proliferative effect in the endometrium, myometrium and vaginal epithelium, causing stimulation of the secretion of glycogen-containing secretion by the endometrial glands, reducing the stroma of the submucosal layer, i.e. causes characteristic changes in the endometrium necessary for implantation of a fertilized egg. Progesterone reduces the tone of the uterine muscles and causes them to relax. In addition, progesterone causes proliferation and development of the mammary glands and during pregnancy helps to suppress the ovulation process. if fertilization does not occur, then after 10-12 days regression of the menstrual corpus luteum occurs, but if the fertilized egg penetrates the endometrium and the resulting blastula begins to synthesize hCG, then the corpus luteum becomes corpus luteum of pregnancy.

Granulosa cells of the corpus luteum secrete the polypeptide hormone relaxin, which takes an important part during childbirth, causing relaxation of the pelvic ligaments and relaxation of the cervix, and also increases glycogen synthesis and water retention in the myometrium, while reducing its contractility.

If fertilization of the egg does not occur, the corpus luteum enters the stage of reverse development, which is accompanied by menstruation. Luteal cells undergo dystrophic changes, decrease in size, and pyknosis of the nuclei is observed. Connective tissue, growing between the disintegrating luteal cells, replaces them, and the corpus luteum gradually turns into a hyaline formation - the white body.

Period of regression of the corpus luteum characterized by a pronounced decrease in the levels of progesterone, estradiol and inhibin A. A decrease in the levels of inhibin A and estradiol, as well as an increase in the frequency of impulses of Gn-RH secretion ensure the predominance of FSH secretion over LH. In response to an increase in FSH levels, a pool of antral follicles is finally formed, from which the dominant follicle will be selected in the future. Prostaglandin F 2 a, oxytocin, cytokines, prolactin and 0 2 radicals have a luteolytic effect, which may be the basis for the development of corpus luteum failure in the presence of an inflammatory process in the appendages. Menstruation occurs against the background of regression of the corpus luteum. By the end of it, the levels of estrogen and progesterone reach their minimum. Against this background, the tonic center of the hypothalamus and pituitary gland is activated and the secretion of predominantly FSH, which activates the growth of follicles, increases. An increase in the level of estradiol leads to stimulation of proliferative processes in the basal layer of the endometrium, which ensures adequate regeneration of the endometrium.

Cyclic changes in the endometrium touch its surface layer, consisting of compact epithelial cells, and the intermediate one, which are rejected during menstruation.

As is known, there is a distinction between phase I - the proliferation phase (early stage - 5-7 days, middle - 8-10 days, late - 10-14 days) and phase II, the secretion phase (early -15-18 day - the first signs of secretory transformations; average - 19-23 days, the most pronounced secretion; late - 24-26 days, beginning regression, regression with ischemia - 26-27 days), phase III, phase bleeding or menstruation (desquamation - 28-2 days and regeneration - 3-4 days).

Fine the proliferation phase lasts 14 days . The changes in the endometrium that occur during this phase are caused by the action of an increasing amount of estrogens secreted by the growing and maturing follicle (Khmelnitsky O.K., 2000).

In the early stage of the proliferation phase(5-7th day of the cycle) the endometrium is thin, there is no division of the functional layer into zones, its surface is lined with flattened cylindrical epithelium, having a cubic shape. Glandular crypts are in the form of straight or slightly convoluted tubes with a narrow lumen; in cross sections they have a round or oval shape. The epithelium of the glandular crypts is prismatic, the nuclei are oval, located at the base, are well stained, the apical edge of the epithelial cells in the light microscope appears smooth and clearly defined.

In the middle stage of the proliferation phase alkaline phosphatase activity increases in the endometrium. Phenomena of edema and loosening are observed in the stroma. The cytoplasm of stromal cells becomes more distinguishable, their nuclei are revealed quite clearly, and the number of mitoses increases compared to the early stage. The stromal vessels are still sporadic, with thin walls.

In the late stage of the proliferation phase(11-14th day of the cycle) some thickening of the functional layer is noted, but division into zones is still absent. The surface of the endometrium is lined with tall columnar epithelium. The glandular structures acquire a more convoluted, corkscrew shape and are more closely adjacent to each other than in the previous stages. The epithelium of glandular crypts is high cylindrical. Its apical edges appear smooth and clear under light microscopy. Electron microscopy reveals microvilli, which are dense cytoplasmic processes covered with a plasma membrane. By increasing in size, they create additional area for the distribution of enzymes. It is at this stage that the activity of alkaline phosphatase reaches its maximum (Topchieva O.I. et al., 1978).

At the end of the proliferation phase light optical examination reveals small subnuclear vacuoles in which small glycogen granules are detected. At this stage, glycogen is formed in connection with the preovulatory secretion of gestagens in the follicle that has reached maturity. The spiral arteries of the stroma, which grow from the basal layer to the middle stage of the proliferation phase, are not yet very tortuous, therefore in histological sections only one or two vessels with thin walls cut across are found (Topchieva O.I. et al., 1978; Zheleznov B. I., 1979).

Thus, estrogens, simultaneously with the proliferation of epithelial cells, stimulate the development of the cell’s secretory apparatus during the proliferation phase, preparing it for further full function in the secretion phase. This explains the sequence of events that has a deep biological meaning. This is why without prior exposure to estrogen on the endometrium, progesterone has virtually no effect. Today it has been revealed that progesterone receptors, which provide sensitivity to this hormone, are activated by the previous action of estrogens.

The secretion phase lasts 14 days, directly related to the hormonal activity of the corpus luteum and the corresponding secretion of progesterone. A shortening or prolongation of the secretion phase by more than two days in women of reproductive age should be considered a pathological condition, since such cycles, as a rule, are anovulatory. Fluctuations in the secretory phase from 9 to 16 days can occur at the beginning or end of the reproductive period, i.e. with the formation or extinction of the utero-ovarian cycle.

In the diagnosis of the 1st week of the secretory phase, changes in the epithelium are of particular importance, allowing us to talk about ovulation that has occurred. Characteristic changes in the epithelium during the first week are associated with the increasing function of the corpus luteum. In the 2nd week, the day of past ovulation can be most accurately determined by the state of the stromal cells. Changes in the 2nd week in the stroma are associated with the highest function of the corpus luteum and its subsequent regression and decrease in progesterone concentration.

During the early stage of the secretion phase(on the 15-18th day of the cycle) the thickness of the endometrium increases noticeably compared to the proliferation phase. The most characteristic sign of the onset of the secretion phase - its early stage - is the appearance of subnuclear vacuoles in the epithelium of the glands. In a conventional light-optical study, the manifestation of secretion in the form of subnuclear vacuoles is usually observed on the 16th day of the cycle, which indicates that ovulation has occurred and the pronounced hormonal function of the menstrual corpus luteum. By the 17th day of the cycle (3rd day after ovulation), glycogen granules are contained in most glands and are located at the same level in the basal regions of the cells under the nucleus. As a result of this, the nuclei located above the vacuoles are also arranged in a row, at the same level. Then, on the 18th day (4th day after ovulation), glycogen granules move to the apical parts of the cells, as if bypassing the nucleus. As a result of this, the nuclei again seem to descend down to the base of the cell. Often by this time, the nuclei in different cells are at different levels. Their shape also changes - they become more rounded, mitoses disappear. The cytoplasm of the cells becomes basophilic, and acidic mucopolysaccharides are detected in their apical part.

The presence of subnuclear vacuoles is a sign of accomplished ovulation. However, we must remember that they are clearly visible under light microscopy 36-48 hours after ovulation. It should be borne in mind that subnuclear vacuoles can also be observed in other situations characterized by the action of progesterone. At the same time, however, they will not be detected in the same way in all glands, and their shape and size will be different. Thus, subnuclear vacuoles are often found in individual glands in the tissue of “mixed” hypoplastic and hyperplastic endometrium.

Along with subnuclear vacuolization, the early stage of the secretion phase is characterized by a change in the configuration of the glandular crypts: they are tortuous, expanded, uniform and regularly located in the loose, somewhat edematous stroma, which indicates the action of progesterone on stromal elements. Spiral arteries in the early stage of the secretion phase acquire a more tortuous appearance, but the “tangles” characteristic of subsequent stages of secretion are not yet observed.

In the middle stage of the secretion phase(19-23rd day of the cycle) the most pronounced secretory transformations are observed in the endometrium, which occur as a result of the highest concentration of corpus luteum hormones. The functional layer is thickened. It clearly shows a division into spongy (spongy) or deep and compact or superficial layers. In the compact layer, the glandular crypts are less tortuous, stromal cells predominate, the epithelium lining the surface of the compact layer is tall, prismatic, and non-secreting. The corkscrew-shaped glandular crypts are quite closely adjacent to each other, their lumens are increasingly expanding, especially by the 21-22nd day of the cycle (that is, by the 7-8th day after ovulation) and become more folded. The process of glycogen release by apocrine secretion into the lumen of the glands ends by the 22nd day of the cycle (8th day after ovulation), which leads to the formation of large, stretched glands filled with fine granules that are clearly visible when stained for glycogen.

In the stroma, during the middle stage of the secretion phase, a decidual-like reaction occurs, noted mainly around the vessels. Then the decidual reaction from the island type acquires a diffuse character, especially in the superficial parts of the compact layer. Connective tissue cells become large, round or polygonal in shape, resembling the appearance of an end pavement; on the 8th day after ovulation, glycogen is found in them.

The most accurate indicator of the middle stage of the secretion phase, indicating a high concentration of progesterone, are changes in the spiral arteries, which in the middle stage of secretion are sharply tortuous and form “tangles”. They are found not only in the spongy, but also in the most superficial parts of the compact layer, since from the 9th day after ovulation the stromal edema decreases, then by the 23rd day of the cycle the tangles of the spiral arteries are already most clearly expressed. The presence of developed spiral vessels in the functional layer of the endometrium is considered one of the most reliable signs that determine the full effect of progesterone. The weak development of “tangles” of spiral vessels in the endometrium of the secretory phase is regarded as a manifestation of insufficient function of the corpus luteum and insufficient preparedness of the endometrium for implantation.

As indicated by O.I. Topchieva et al. (1978), the structure of the endometrium of the middle stage secretory phase on the 22-23rd day of the cycle can be observed with prolonged and increased hormonal function of the menstrual corpus luteum, i.e. with persistence of the corpus luteum (in such cases, the juiciness and decidual-like transformation of the stroma, as well as the secretory function of the glands, are especially pronounced), or in the early stages of pregnancy during the first days after implantation - with intrauterine pregnancy outside the implantation zone; as well as evenly in all parts of the mucous membrane of the uterine body with progressive ectopic pregnancy.

Late stage of the secretion phase(24-27th day of the cycle) occurs if fertilization of the egg has not occurred and pregnancy has not occurred. In this case, on the 24th day of the cycle (10th day after ovulation), the trophism of the endometrium, due to the onset of regression of the corpus luteum and, accordingly, a decrease in the concentration of progesterone, is disrupted, and a number of dystrophic processes develop in it, i.e. Regressive changes occur in the endometrium.

With conventional light-optical microscopy, 3-4 days before the expected menstruation (on the 24-25th day of the cycle), a decrease in the juiciness of the endometrium is noted due to loss of fluid, and wrinkling of the stroma of the functional layer is observed. Due to the wrinkling of the endometrial stroma, the glands become even more folded, are closely located to each other and acquire a sawtooth shape on longitudinal sections, and a star-shaped outline on transverse sections. Along with the glands in which the secretory function has already ceased, there is always a certain number of glands with a structure corresponding to the earlier stages of the secretory phase. The epithelium of glandular crypts is characterized by uneven coloring of the nuclei, some of which are pyknotic; small drops of lipids appear in the cytoplasm.

During this period, in the stroma, predecidual cells come closer to each other and are detected not only in the form of islands around tangles of spiral vessels, but also diffusely throughout the compact layer. Among the predecidual cells, small cells with dark nuclei are found - endometrial granular cells, which, as shown by electron microscopic studies, are transformed from connective tissue cells, i.e. larger predecidual cells, which are located predominantly in a compact layer. In this case, the cells are depleted of glycogen, their nuclei become pyknotic.

On the 26-27th day of the cycle, expansion of capillaries and hemorrhages in the superficial layers can be detected in the stroma. This is because as the cycle progresses, the spiral arterioles lengthen faster than the thickness of the endometrium increases, so that the vessels adapt to the endometrium by increasing tortuosity. During the premenstrual period, coiling becomes so pronounced that it slows blood flow and causes stasis and thrombosis. This point, along with a number of other biochemical processes, explains endometrial necrosis and dystrophic changes in blood vessels that lead to menstrual bleeding. Shortly before the onset of menstruation, vasodilation is replaced by spasm, which is explained by the action of various types of toxic products of protein breakdown or other biologically active substances against the background of a drop in progesterone levels.

Bleeding phase, menstruation(28-4th day of the cycle), characterized by a combination of desquamation and regeneration processes.