Embryogenesis of the reproductive system. Development of the female reproductive system. Stages of pituitary gland development

Sex formation is the process of development of many characteristics and properties that distinguish males from females and prepare them for reproduction. Sexual differentiation covers a number of stages of the embryonic and postembryonic periods.

The formation of the reproductive tract in embryogenesis is determined by the interaction of three groups of factors: the genetic mechanism, internal epigenetic factors (enzyme systems, hormones) and external epigenetic factors reflecting the influence of the external environment.

The concept of “sex” is made up of a number of interconnected biological, mental and social components.

The genetic sex of the unborn child is predetermined at the moment of fusion of the egg and sperm and is determined by the set of sex chromosomes formed in the zygote when the maternal and paternal gametes are combined (XX - female, XY - male), and a set of special genes that determine primarily the type of gonads, the level of enzyme activity systems, tissue reactivity to sex hormones, synthesis of sex hormones.

Male and female gonads develop from one undifferentiated rudiment. Until 6 weeks of embryonic life, it is morphologically the same for both females and males and consists of a cortical and medulla layer. Subsequently, the ovary is formed from the cortical layer, and the testicle is formed from the medulla.

It has now been proven that the gene that determines the differentiation of the gonad primordium according to the male type determines the biosynthesis of a specific membrane protein, the H-Y antigen. The cells of the developing organism, including the cells covering the surface of the primordial gonad, contain receptors for the H-Y antigen. Uptake of H-Y antigen by these cells induces the development of the primary gonad into the testis. In the experiment, the introduction of the H-Y antigen into the undifferentiated gonad of females induces the development of testicular tissue. There is an opinion that the morphogenesis of the gonad is regulated not by one, but by several genes, and one H-Y antigen is not enough for complete differentiation of the testis. At least 18 genes are proposed to be required for the prenatal development of the male phenotype.

The differentiation of the primary gonad into the ovary is not a passive process, but is induced by specific molecules corresponding to the H-Y antigen in the male. In ovarian differentiation, a certain role is played by loci of the X chromosome located in the region of its centromere, closer to the short arms of the chromosome.

The development of the male and female gonads begins in the same way, with the formation of genital ridges - future gonads - on the medial side of the primary bud. The elements of the developing gonads are gonocytes, giving rise to oogonia and spermatogonia, derivatives of the coelomic epithelium - the future epithelial elements of the gonads and mesenchymal tissue - the future connective tissue and muscle elements of the gonads [Volkova O. V., Pekarsky M. I., 1976] (Fig. 1). The interstitial tissue of the gonad, derived from mesenchymal cells, forms Leydig cells in male embryos, and theca tissue in female embryos.

Differentiation of the testicle begins somewhat earlier than the ovary, since the high hormonal activity of the fetal testicle is necessary for the further formation of the reproductive tract of the male fetus. The ovaries are hormonally inactive during intrauterine life. Thus, gonadal differentiation is determined by genes located on the sex chromosomes.

The next stage of sexual formation is the differentiation of internal and external genitalia. In the early stages of embryogenesis, the reproductive system has bisexual anlages of the internal and external genitalia. The internal genital organs differentiate at the 10-12th week of the intrauterine period. The basis of their development are the indifferent mesonephric (Wolffian) and paramesonephric (Müllerian) ducts.

During the development of a female fetus, the mesonephric ducts regress, and the paramesonephric ducts differentiate into the uterus, oviducts, and vaginal vault (Fig. 2). This is facilitated by the autonomous tendency of any fetus towards feminization (development according to the female, “neutral” type). The fallopian tubes are formed in the form of paired formations from the Müllerian cords that have not fused in the upper third, while the uterus and vagina are formed as a result of the fusion of the Müllerian ducts. The fusion of the Müllerian ducts begins from the caudal end by the 9th week of embryogenesis. The completion of the formation of the uterus as an organ occurs by the 11th week. The uterus is divided into the body and cervix at the end of the 4th month of intrauterine development [Fedorova N.N., 1966].

During the development of a male fetus, the paramesonephric ducts regress, and the mesonephric ducts differentiate into the epididymis, seminal vesicles, and vas deferens. The formation of the reproductive tract according to the male type is possible only in the presence of a full-fledged, active embryonic testicle. The paramesonephric (Müllerian) ducts in male embryos regress under the influence of a factor synthesized by the fatal testes and called “Müller-suppressing substance”, “anti-Müllerian factor”. This factor is different from testosterone and is a thermolabile macromolecular product of Sertoli cells lining the walls of the seminiferous tubules. The Müllerian canal regression factor is protein in nature, nonspecific and belongs to glycoproteins. Anti-Mullerian factor activity persists in the testes throughout intrauterine life and even after birth. When studying the inhibitory effect of human testicular tissue on the development of paramesonephric ducts of a female rat embryo, the activity of testicular tissue was highest in children under 5 months, and then gradually decreased. After 2 years, anti-Mullerian factor activity was not detected. However, the paramesonephric ducts are sensitive to the regression factor for a very short time and already in the postnatal period this sensitivity disappears. Mesonephric (Wolfian) ducts persist and differentiate into epididymis, seminal vesicles, and vas deferens only when there is a sufficient amount of androgens produced by the fetal testes. Testosterone does not interfere with the differentiation of paramesonephric (Müllerian) leaks.

The external genitalia are formed from the 12th to the 20th week of the intrauterine period. The basis for the development of the external genital organs of fetuses of both sexes are the genital tubercle, labioscrotal ridges and urogenital sinus (Fig. 3). In the female fetus, differentiation of the external genitalia occurs regardless of the state of the gonads. During this period, the vagina (its caudal 2/3), clitoris, labia majora and minora, vestibule of the vagina with separate external opening of the urethra and the entrance to the vagina are formed.

The formation of the external genitalia of a male fetus occurs normally only when the functional activity of the embryonic testes is sufficiently high. Androgens are necessary for the differentiation of embryonic anlages according to the male type: the urogenital sinus - into the prostate gland and urethra, the urogenital tubercle - into the penis, the corpora cavernosa, the genital ridges - into the scrotum, the mesonephric duct - into the epididymis, the vas deferens, the seminal vesicle. Masculinization of the external genitalia in the male fetus also consists of atrophy of the vaginal process of the urogenital sinus, fusion of the scrotal suture, enlargement of the corpora cavernosa of the penis and the formation of the male-type urethra. The descent of the testicles from the abdominal cavity begins from the 3rd month of embryonic life, and by 8-9 months the testicles descend into the scrotum. Their descent is caused by both mechanical factors (intra-abdominal pressure, atrophy and shortening of the inguinal cord, uneven growth of the structures involved in this process) and hormonal factors (the influence of placental gonadotropins, androgens of the fetal testicles, gonadotropic hormones of the fetal pituitary gland) [Bodemer Ch., 1971; Eskin I.A., 1975]. The descent of the testicles coincides with their maximum androgenic activity.

EMBRYOGENESIS OF THE URINARY TRACT AND GENITAL ORGANS

The urinary tract and genital organs develop together from common anlages. To facilitate the perception of information, we consider the embryogenesis of the kidneys and ureters, bladder and urethra, gonads, genital ducts and external genitalia separately.
KIDNEYS AND URETERS
Kidney development in humans goes through three stages - pre-bud, primary and final kidney (Fig. 2.1).
Predpochka
The kidney, an analogue of the excretory organ in lower vertebrates, is formed at the level of the 4th–14th somites. The preference consists of 6-10 pairs of tubules flowing into paired excretory ducts, which are formed at the same level, grow in the caudal direction and empty into the cloaca. In humans, the preference kidney does not function and disappears by the 4th week of embryogenesis.
Primary kidney
The primary kidney, an analogue of the excretory organ in bony fish and amphibians, is formed at the beginning of the 4th week, reaches its maximum size by the end of the 8th week of embryogenesis and functions throughout this entire period. The primary bud gradually undergoes reverse development. The only exception is the Wolffian duct (duct of the primary kidney), which gives rise to the male genital organs. The tubules of the primary kidney are formed from the mesoderm caudal to the adrenal bud shortly before its disappearance. Unlike the tubules of the prerenal, each tubule of the primary kidney on one side forms a blind cup-shaped outgrowth (glomerular capsule), into which capillaries (glomerulus) are immersed. On the other side, each tubule connects with the nearest duct of the anterior kidney, which opens into the cloaca. From now on it is called the Wolffian duct. Then the tubules of the primary kidney elongate, take an S-shape and branch. This increases the area of ​​their contact with the capillaries. Blood from the glomerulus flows through one or more efferent vessels, which again break up into capillaries, forming a dense network around the tubules of the primary kidney.
The final bud
The final bud is formed from metanephrogenic tissue (derivative of mesoderm) and Wolffian proto-

6th week

Start of 4th week

Prerenal degeneration

Predpochka

Undifferentiated metanephrogenic tissue

Rectum

Cloaca

Ureteral growth

Urogenital sinus

Figure 2.1. Embryogenesis of the kidneys and ureters. At the beginning of the 4th week, some of the tubules of the prerenal are preserved, but the tubules of the primary kidney are already formed, which connect to the Wolffian duct. A ureteric process appears in the caudal part of the Wolffian duct. By the 6th week, the preference kidney disappears and degeneration of the primary kidney tubules begins. The ureteric process grows in the dorsocranial direction and grows into the metanephrogenic tissue. At the 8th week, the final bud moves upward. The cranial end of the ureteric process expands and gives off numerous branches.

to a. Development of the final bud begins when the embryo is 5-6 mm long. First, at the point where the Wolffian duct bends before it enters the cloaca, a ureteric outgrowth appears. The ureteric process elongates in the cranial direction, capturing metanephrogenic tissue. As you grow ureteral As the outgrowth grows, the metanephrogenic tissue also moves further and further in the cranial direction. At the same time, it grows and quickly differentiates. The cranial end of the ureteric process in the thickness of the metanephrogenic tissue expands, forming the renal pelvis. Many blind branches extend radially from the renal pelvis, which, in turn, also branch, forming collecting ducts. Metanephrogenic tissue cells form clusters around the blind ends of the collecting ducts. In these clusters, central cavities form, and they themselves become S-shaped and connect to the collecting ducts, forming continuous tubular structures. One part of each S-shaped cluster of cells turns into the proximal and distal convoluted tubules and the loop of Henle, the other into the glomerulus and its capsule. As the final bud grows, more and more tubules are formed at its periphery. At this stage of embryogenesis, the mesoderm and the developing glomeruli are clearly visible under the microscope (Fig. 2.2). The development of the glomeruli ends by the 36th week, when the fetus weighs about 2500 g. The final bud is formed at the level of the 28th somite (L4 vertebra), and by the time of birth it rises to the L1 or TH2 vertebra. This is partly due to the cranial displacement of the kidney, partly due to the rapid growth of the caudal part of the fetus. At the beginning of the cranial displacement (7-9 weeks), the kidneys pass over the aortic bifurcation and rotate 90° around the longitudinal axis, while their convex dorsal surface becomes lateral. After rotation, the rate of cranial displacement slows down.
Thus, kidney embryogenesis has the following features.
The prebud, primary and final bud develop from the mesoderm.
The tubules always form in isolation and then connect to the excretory ducts.
Prerenal ducts are formed at the level of the prerenal tubules.
The ducts of the prerenal organ give rise to the Wolffian ducts and hence the ureters.
Prerenal ducts grow in a caudal direction and empty into the cloaca.
The ureters are formed from outgrowths of the Wolffian ducts, and the renal tubules are formed from metanephrogenic tissue.
Developmental defects
Violation of cranial displacement leads to kidney dystopia. If the kidney is located on its side,
they talk about homolateral dystopia, if on the opposite side - about heterolateral. In the latter case, fusion of the kidneys is possible. Since the processes of cranial displacement and rotation of the kidney occur simultaneously, kidney dystopia is usually combined with incomplete rotation. Fusion of metanephrogenic tissue leads to fusion of the kidneys, most often to the formation of a horseshoe kidney.
When the ureteral process is split, incomplete duplication of the ureter occurs. If an accessory ureteric projection departs from the Wolffian duct, complete doubling of the ureter is observed, with both ureteric projections, as a rule, contacting one area of ​​metanephrogenic tissue. Occasionally there are two ureteric outgrowths and two areas of metanephrogenic tissue. As a result, an additional bud is formed. During duplication, the main ureter is formed first in the caudal part of the Wolffian duct and drains the lower pole of the kidney. The accessory ureter drains the upper pole of the kidney, but enters the bladder caudal to the main one. Thus, according to the Weigert-Meyer law, duplicate ureters always intersect. If the main and accessory ureteral processes depart from the Wolffian duct nearby, the orifices of the ureters are also located nearby. If the accessory ureteric outgrowth is located far from the main one, the mouth of the accessory ureter is located in the neck of the bladder, urethra or in the genitals (Fig. 2.3). Ectopic ureter also occurs when the ureteric protrusion extends from the Wolffian duct higher than normal. If there is no ureteral process on any side, unilateral renal agenesis develops and only half of the bladder triangle is formed.

BLADDER AND URENARY CHANNEL

The expansion of the blind end of the hindgut caudal to the allantois forms the cloaca, which is separated from the amnion by a thin plate - the cloacal membrane. The latter lies in the recess of the ectoderm under the base of the tail. When the length of the embryo reaches 4 mm, at the junction of the allantois and the hindgut, a crescent-shaped fold begins to grow into the lumen of the cloaca in the caudal direction, which gradually forms the urogenital septum. At the 7th week of embryogenesis, it completely divides the cloaca: the urogenital sinus is formed ventrally, and the rectum is formed dorsally. During the formation of the urogenital septum, the outer ectodermal surface of the cloacal membrane, first facing the anterior abdominal wall, shifts caudally and backward. This occurs due to the development of the lower part of the anterior abdominal wall of the embryo and the disappearance of the tail and contributes to the formation of the urinary rectum

Partitions. As a result of the proliferation of mesoderm in the area of ​​the cloacal membrane and the attachment of the umbilical cord, an elevation is formed - the genital tubercle. As the lower part of the anterior abdominal wall develops, the genital tubercle and the site of attachment of the umbilical cord diverge further and further. The cloacal membrane disappears only after the cloaca is divided, so the urogenital sinus and rectum open outward with separate openings. The urogenital sinus has a cylindrical shape, communicates cranially with the allantois and
opens outward through the urogenital opening. The rectum opens outward through the anus.
Wolffian ducts gradually grow into the urogenital sinus. By the 7th week of embryogenesis, the Wolffian ducts and ureters open into the urogenital sinus with separate openings. An accumulation of mesoderm appears between them. Then the openings of the Wolffian (future ejaculatory) ducts shift downward and medially, and the openings of the ureters move upward and laterally. The accumulation of mesoderm described above is

Figure 2.2. Development of nephrons. A cluster of metanephrogenic tissue cells forms around each collecting duct. Later, a cavity is formed inside each of them. Renal tubules develop from clusters of metanephrogenic tissue cells. On the one hand, they connect to the nearest collecting duct, and on the other, they form the glomerulus and its capsule.

appears to be limited by the openings of the Wolffian ducts and ureters (Fig. 2.3). In the future, a triangle of the bladder is formed from it. Thus, the epithelium of the triangle of the bladder is of mesodermal origin, while the rest of the epithelium of the bladder and urethra is of endodermal origin.
The urogenital sinus has two segments. They are separated by a plane passing through the Müllerian tubercle (see below). It is formed on the dorsal wall of the urogenital sinus, where the fused Müllerian ducts come into contact with it. The first segment includes the ventral
and the pelvic sections of the urogenital sinus, where the ureters drain. From this segment the bladder, the female urethra and part of the male urethra are formed. The second segment is formed by the urethral portion of the urogenital sinus. The Wolffian and fused Müllerian ducts contact it. From this segment are formed part of the male urethra, the distal part of the vagina (one fifth) and the vestibule of the vagina.
At the 3rd month of embryogenesis, the ventral section of the urogenital sinus expands and turns into an epithelial sac, the apex of which narrows, forming the urinary duct. The pelvic portion of the urogenital sinus remains as a narrow tube and forms the female urethra or the prostatic portion of the male urethra proximal to the spermatic colliculus. The mesoderm surrounding the ventral and pelvic sections of the urogenital sinus differentiates into smooth muscle cells and an outer connective tissue membrane. By the 12th week of embryogenesis, the wall of the urethra and bladder is completely formed (Fig. 2.4).

The urethral section of the urogenital sinus forms the distal part of the vagina, its vestibule (Fig. 2.5.), as well as the distal section (distal to the seminal colliculus) of the prostate and the membranous part of the male urethra. The spongy part of the urethra is formed by the ventral fusion of the urogenital folds. In female fetuses, the urogenital folds do not fuse and become the labia minora. The bladder first reaches the umbilicus, where it connects with the allantois.

Figure 2.3. Development of ureteric outgrowths. Ureteral outgrowths appear in the 4th week of embryogenesis. The sections of the Wolffian ducts located caudal to them form the wall of the urogenital sinus. As a result, the ureters and Wolffian ducts open into the urogenital sinus with separate openings. The part of the Wolffian duct involved in the formation of the urogenital sinus forms the triangle of the bladder.

Figure 2.4. Differentiation of the urogenital sinus in male fetuses. At the 5th week of embryogenesis, the urogenital septum separates the rectum and the urogenital sinus, into which the Wolffian ducts and ureteric processes flow. The wall of the urogenital sinus remains in its original form until the 12th week. Then the muscular layer begins to form from the surrounding mesenchyme. The prostate gland develops from multiple epithelial outgrowths of the developing urethra cranial and caudal to the Wolffian ducts. At the 3rd month of embryogenesis, the ventral part of the urogenital sinus expands, forming the bladder. Part of the male urethra is formed from the narrow pelvic region. Tanagho EA, Smith DR: Mechanisms of urinary continence. 1. Embryologic, anatomic, and pathologic considerations. Jurol 1969 ,100:640 .

By the 15th week of embryogenesis, the allantois at the level of the navel is obliterated. By the 18th week, the bladder begins to move downward. Its apex stretches, narrows and carries with it the obliterated allantois, which is now called the urinary duct. By the 20th week of embryogenesis, the bladder is significantly removed from the navel, and the urinary duct forms the median umbilical ligament.

Developmental defects

If the cloaca does not divide during embryogenesis, a rare developmental defect is observed - congenital cloaca. More often, due to incomplete division of the cloaca, congenital fistulas are formed between the rectum and the bladder, urethra or vagina. As a rule, this is combined with anal atresia.

Impaired downward displacement of the bladder and non-closure of the urinary duct lead to the formation of a vesico-umbilical fistula or cyst or diverticulum of the urinary duct.

If the genital tubercle is laid more caudal than normal, then the cavernous bodies are formed caudal to the urogenital sinus. As a result, the urogenital groove appears on the dorsal surface of the cave

corpora and remains partially or completely open (epispadias). With complete epispadias, the entire anterior wall of the urethra, up to the bladder, is absent. An even more severe malformation is bladder exstrophy - the absence of the anterior wall of the bladder and part of the anterior abdominal wall. Violation of the fusion of the urogenital folds causes hypospadias - partial or complete absence of the posterior wall of the spongy part of the urethra.

I. Embryonic development of the organs of the male reproductive system. The formation and development of the reproductive system is closely connected with the urinary system, namely with the first kidney. The initial stage of the formation and development of the organs of the reproductive system in males and females proceeds in the same way and is therefore called the indifferent stage. At the 4th week of embryogenesis, the coelomic epithelium (visceral layer of splanchnotomes) on the surface of the first kidney thickens - these thickenings of the epithelium are called genital ridges. Primary germ cells, gonoblasts, begin to migrate into the genital ridges. Gonoblasts first appear as part of the extraembryonic endoderm of the yolk sac, then they migrate to the wall of the hindgut, and there they enter the bloodstream and reach and penetrate into the genital ridges through the blood. Subsequently, the epithelium of the genital ridges, together with gonoblasts, begins to grow into the underlying mesenchyme in the form of cords - the genital cords are formed. The reproductive cords consist of epithelial cells and gonoblasts. Initially, the sex cords retain contact with the coelomic epithelium, and then break away from it. Around the same time, the mesonephric (Wolffian) duct (see embryogenesis of the urinary system) splits and the paramesanephric (Müllerian) duct is formed parallel to it, which also flows into the cloaca. This is where the indifferent stage of development of the reproductive system ends.
Subsequently, the reproductive cords fuse with the tubules of the first kidney. From the reproductive cords the epitheliospermatogenic layer of convoluted seminiferous tubules of the testicle is formed (from gonoblasts - germ cells, from coelomic epithelial cells - sustenotocytes), the epithelium of the straight tubules and the testicular network, and from the epithelium of the first kidney - the epithelium of the efferent tubules and the epididymal canal. The vas deferens is formed from the mesonephric duct. From the surrounding mesenchyme, a connective tissue capsule, the tunica albuginea and the mediastinum of the testicle, interstitial cells (Leydig), connective tissue elements and myocytes of the vas deferens are formed.
The seminal vesicles and prostate gland develop from protrusions of the wall of the urogenital sinus (part of the cloaca separated from the anal rectum by the urorectal fold).
The serous covering of the testicles is formed from the visceral layer of the splanchnotomes.
The paramesonephric (Müllerian) duct does not take part in the formation of the male reproductive system and, for the most part, undergoes reverse development, only from its most distal part does the rudimentary male uterus form in the thickness of the prostate gland.
Male gonads (testes) are laid on the surface of the first kidney, i.e. in the abdominal cavity in the lumbar region, retroperitoneal. As it develops, the testicle migrates down the posterior wall of the abdominal cavity, becomes covered with the peritoneum, passes through the inguinal canal at approximately the 7th month of embryonic development, and shortly before birth descends into the scrotum. Impaired descent of one testicle into the scrotum is called monorchidism, and failure of both testicles to descend into the scrotum is called cryptorchidism. Sometimes, in the future, the testicle(s) may spontaneously descend into the scrotum, but more often it is necessary to resort to surgical intervention. From a morphological point of view, such an operation should be performed before the age of 3 years, since it is at this time that a gap appears in the sex cords, i.e. the sex cords turn into convoluted seminiferous tubules. If the testicle does not descend into the scrotum, then at 5-6 years of age irreversible dystrophic changes begin in the spermatogenic epithelium. Leading subsequently to male infertility.

II. Histological structure of the testes ( testicles). The outside of the testicle is covered with peritoneum; under the peritoneal membrane there is a capsule of dense, unformed fibrous connective tissue - the tunica albuginea. On the lateral surface, the tunica albuginea thickens - the mediastinum of the testicle. Connective tissue septa extend radially from the mediastinum, dividing the organ into lobules. Each lobule contains 1-4 convoluted seminiferous tubules, which in the mediastinum, merging with each other, continue into straight tubules and tubules of the testicular network.

The convoluted seminiferous tubule is lined from the inside with an epitheliospermatogenic layer and is covered from the outside by its own membrane.
The epitheliospermatogenic layer of the convoluted seminiferous tubules consists of 2 cell differentials: sprematogenic cells and supporting cells.
Spermatogenic cells are germ cells at various stages of spermatogenesis:
a) dark stem spermatogonia type A – slowly dividing, long-lived reserve stem cells; located in the most peripheral zones of the tubule (closer to the basement membrane);
b) light stem spermatogonia of type A - rapidly renewing cells, are at the first stage of spermatogenesis - the stage of reproduction;
c) in the next layer, closer to the lumen of the tubule, there are first-order spermatocytes at the growth stage. Light stem spermatogonia of type A and first-order spermatocytes remain connected to each other using cytoplasmic bridges - the only example in the human body of a special form of organization of living matter - syncytium;
d) in the next layer, closer to the lumen of the tubule, there are cells at the stage of maturation: a spermatocyte of the first order undergoes 2 divisions in rapid succession (meiosis) - as a result of the first division, spermatocytes of the second order are formed, the second division - spermatids;
e) the most superficial cells of the seminiferous tubules - spermatozoa are formed from spermatids during the last stage of spermatogenesis - the formation stage, which ends only in the epididymis.
The total duration of maturation of male germ cells from a stem cell to a mature sperm is about 75 days.
The second differential of the epitheliospermatogenic layer is supporting cells (synonyms: sustentocytes, Sertoli cells): large pyramid-shaped cells, oxyphilic cytoplasm, irregularly shaped nucleus, the cytoplasm contains trophic inclusions and almost all organelles of general purpose. The cytolemma of Sertoli cells forms bay-shaped invaginations into which maturing germ cells are immersed. Functions:
- trophism, nutrition of germ cells;
- participation in the production of the liquid part of sperm;
- are part of the blood-testicular barrier;
- supporting-mechanical function for germ cells;
- under the influence of follitropin (FSH), the adenohypophysis synthesizes androgen binding protein (ABP) to create the necessary concentration of testosterone in the convoluted seminiferous tubules;
- synthesis of estrogens (by aromatization of testosterone);
- phagocytosis of degenerating germ cells.
The epitheliospermatogenic layer is located on the usual basement membrane, then outward follows the tubular lining, in which 3 layers are distinguished:
1. The basal layer is made up of a network of thin collagen fibers.
2. Myoid layer - from 1 layer of myoid cells (they have contractile actin fibrils in the cytoplasm) on their own basement membrane.
3. The fibrous layer - closer to the basement membrane of myoid cells consists of collagen fibers, further closer to the surface - of fibroblast-like cells.
Outside, the convoluted seminiferous tubules are entwined with hemo- and lymph capillaries. The barrier between the blood in the capillaries and the lumen of the convoluted seminiferous tubules is called the hemotesticular barrier, consisting of the following components:
1. Hemocapillary wall (endotheliocyte and basement membrane).
2. The proper shell of the convoluted seminiferous tubule (see above) of 3 layers.
3. Cytoplasm of sustentocytes.
The blood-testis barrier performs the following functions:
- helps maintain a constant concentration of nutrients and hormones necessary for normal spermatogenesis;
- does not allow A-genes of germ cells to pass into the blood, and from the blood to maturing germ cells - possible A-bodies against them;
- protection of maturing germ cells from toxins, etc.
In the testicular lobules, the spaces between the convoluted seminiferous tubules are filled with interstitial tissue - layers of loose fibrous connective tissue containing special endocrine cells - interstitial cells (synonyms: glandulocytes, Leydig cells): large round cells with weakly oxyphilic cytoplasm. Under an electron microscope: agranular EPS and mitochondria are well defined; by origin - mesenchymal cells. Leydig cells produce male sex hormones - androgens (testosterone, dihydrotestosterone, dihydroepiandrosterone, androstenedione) and female sex hormones - estrogens, which regulate secondary sexual characteristics. The function of Leydig cells is regulated by the adenopituitary hormone lutropin.
The process of spermatogenesis is very sensitive to the effects of unfavorable factors: intoxication, hypo- and avitaminosis (especially vitamins A and E), malnutrition, ionizing radiation, prolonged exposure to a high-temperature environment, a febrile state with high body temperature lead to destructive changes in the spermatozoa. tubules.

III. Epididymis (epidedymis). The seminal fluid enters the epididymis through the efferent tubules, which form the head of the epididymis. The efferent tubules in the body of the organ merge with each other and continue into the appendage canal. The efferent tubules are lined with a peculiar epithelium, where cuboidal glandular epithelium alternates with prismatic ciliated epithelium, therefore the contour of the lumen of these tubules in a cross section is folded or “jagged”. The middle shell of the efferent tubules consists of a thin layer of myocytes, the outer shell is made of loose connective tissue.
The appendage canal is lined with 2-row ciliated epithelium, therefore the lumen of the canal on the cut has a smooth surface; in the middle shell, compared to the efferent tubules, the number of myocytes increases. Functions of the appendage:
- organ secretion dilutes sperm;
- the stage of spermatogenesis formation is completed (spermatozoa are covered with glycocalyx and acquire a negative charge);
- reservoir function;
- reabsorption of excess fluid from sperm.

IV. Prostate gland (prostate) – in the embryonic period it is formed by protrusion of the wall of the urogenital sinus and surrounding mesenchyme. It is a muscular-glandular organ that surrounds the urethra in the form of a sleeve immediately after exiting the bladder. The glandular part of the organ is represented by alveolar-tubular end sections, lined with tall cylindrical endocrinocytes, and excretory ducts. The secretion of the gland dilutes sperm, causes capacitation of sperm (activation, acquisition of mobility), contains biologically active substances and hormones that affect the functions of the testicle.
In old age, hypertrophy of the glandular part of the prostate (prostate adenoma) is sometimes observed, which leads to compression of the urethra and difficulty urinating.
The spaces between the secretory sections and excretory ducts of the gland are filled with layers of loose connective tissue and smooth muscle cells.
Male sex hormones androgens cause hypertrophy and enhance the secretory function of the prostate glands, and female sex hormones estrogens, on the contrary, suppress the function of these glands and lead to the degeneration of tall columnar secretory cells into non-secretory cubic epithelium, therefore, for malignant prostate tumors, the use of estrogens and castration is indicated (stopped androgen production).

Vas deferens– the mucous membrane is lined with multi-row ciliated epithelium, under the epithelium is its own plastic made of loose connective tissue. The middle shell is muscular, very highly developed; the outer shell is adventitial.

Seminal vesicles– develop as a protrusion of the wall of the urogenital sinus and mesenchyme. It is a long, highly convoluted tube, the inside is lined with glandular high columnar epithelium, the middle layer is smooth muscle. The secretion of the glands dilutes the sperm and contains nutrients for sperm.

The topic “Male reproductive system” is discussed in four mini-lectures:

1. Male gonads - testicles

2. Spermatogenesis. Regulation of testicular activity

3. Vas deferens. Accessory glands.

4. Development of the male reproductive system.

Below the lectures are the text.

1. MALE GONADS - TESTLES

2. SPERMATOGENESIS. ENDOCRINE REGULATION OF TESTICAL ACTIVITY

3. Vas deferens. Accessory glands

Development of the male reproductive system

The formation of the reproductive system in the initial stages of embryogenesis (up to the 6th week) occurs in the same way in both sexes, moreover, in close contact with the development of the urinary and urinary organs. At the 4th week, thickening of the coelomic epithelium, which covers the kidney, forms on the inner surfaces of both primary kidneys - genital ridges. Epithelial cells of the ridge, giving rise to follicular cells of the ovary or sustentocytes of the testicle, move deep into the kidney, surround gonocytes migrating here from the yolk sac, forming sex cords ( future ovarian follicles or testicular convoluted tubules). Mesenchymal cells accumulate around the sex cords, giving rise to the connective tissue septa of the gonads, as well as ovarian thecocytes and testicular Leydig cells. From both at the same time mesonephric (Wolffian) ducts of both primary buds, stretching from the kidney bodies to the cloaca, are split off running parallel paramesonephric (Müllerian) ducts.

Thus, by the 6th week, the indifferent gonad contains the precursors of all the main structures of the gonads: sex cords, consisting of gonocytes surrounded by epithelial cells, around the sex cords are mesenchymal cells. Cells of the indifferent gonad are sensitive to the action of the Y chromosome gene product, which is designated as testis-determining factor (TDF). Under the influence of this substance, in the 6th week of embryogenesis, the testicle develops: the sex cords occupy a central position in the gonad, the renal tubules of the primary kidney turn into the initial sections of the vas deferens, the precursors of sustentocytes produce Mullerian inhibitory factor (MIF-substantia), under the influence of which the paramesonephric ducts atrophy , while the mesonephric ones become the vas deferens.

1. Testicle (testis)

Testicle(testis) performs two functions: 1) generative: formation of male germ cells - spermatogenesis, and2) endocrine: production of male sex hormones.

The testis has a connective tissue capsule and is covered on the outside with a serous membrane. Connective tissue septa extend from the capsule into the organ, dividing the organ into 150-250 lobules. Each lobule has 1-4 convoluted seminiferous tubules, where spermatogenesis directly occurs. The wall of the convoluted tubule consists of spermatogenic epithelium located on the basement membrane, a layer of myoid cells and a thin fibrous layer separating the tubule from the interstitial tissue.

Spermatogenic epithelium The convoluted tubule consists of two types of cells: developing sperm and sustentocytes. Among spermatogenic cells sustentocytes(supporting cells, Sertoli cells) are the only type of non-spermatogenic cells of the spermatogenic epithelium. Supporting cells, on the one hand, are in contact with the basement membrane, and on the other, lie between the developing sperm.

Sustentocytes have large and numerous finger-like projections that can simultaneously contact a large number of sperm precursors at different stages of development: spermatogonia, first- and second-order spermatocytes, spermatids. With their processes, sustentocytes divide the spermatogenic epithelium into two sections: basal, which contains spermatogenic cells that have not entered meiosis, that is, in the first stages of development, and adluminal a section located closer to the lumen of the tubule and containing spermatogenic cells in the last stages of development.

The myoid cells of the convoluted tubule, contracting, promote the movement of sperm in the direction of the seminiferous ducts, the beginning of which are the straight tubules and the rete testis.

Between the tubules in the testis there is loose fibrous connective tissue containing blood vessels, nerves and interstitial glandulocytes (Leydig cells), producing male sex hormones – androgens.

Cytological characteristics of the main phases of spermatogenesis. Spermatogenesis consists of four successive stages: 1) reproduction, 2) growth, 3) maturation, 4) formation.

Breeding phase characterized by the division of spermatogonia, activated at the beginning of puberty and almost constantly dividing by mitosis in the basal part of the convoluted tubule. There are two types of spermatogonia: A and B. According to the degree of chromatin condensation in the nuclei type A spermatogonia divisible by 1) dark– these are resting, true stem cells, 2) light- These are dividing semi-stem cells that undergo 4 mitotic divisions. Spermatogonia are the most sensitive cells of the testicle. Many factors (including ionizing radiation, overheating, alcohol intake, fasting, local inflammation) can easily cause their degenerative changes.

By their last division, type A spermatogonia turn into type B spermatogonia(2с,2n), and after the final division they become 1st order spermatocytes.

Spermatocytes of the 1st order are connected to each other using cytoplasmic bridges, which are formed as a result of incomplete cytotomy during division, which contributes to the synchronization of development processes and nutrient transfer. Such an association of cells (syncytium), formed by one spermatogonia A (maternal), moves from basal section tubule in adluminal.

2) Growth phase. Spermatocytes of the 1st order increase in volume, doubling of the genetic material occurs - 2c4n. These cells enter a long (about 3 weeks) prophase of the 1st meiotic division, which includes the stages of leptotene, zygotene, pachytene, diplotene and diakinesis. In the interphase before meiosis and in the early stages of prophase of the 1st division of meiosis, the 1st order spermatocyte is located in the basal part of the convoluted tubule, and then in the adluminal section, since crossing over occurs during pachytene - the exchange of parts of paired chromatids, providing genetic diversity of gametes and the cell becomes different from other somatic cells of the body.

3) Maturation phase characterized by the completion of the 1st division of meiosis: spermatocytes of the 1st order finish prophase, go through metaphase, anaphase, telophase, as a result of which from one spermatocyte of the 1st order two spermatocytes of the 2nd order (1c2n) are formed, which are smaller compared to spermatocytes are of the 1st order in size, located in the adluminal part of the convoluted tubule and have a diploid set of DNA.

Spermatocytes of the 2nd order exist for only one day, which makes them practically invisible on a histological specimen, in contrast to the large number of spermatocytes of the 1st order in a section of a convoluted tubule. Spermatocytes of the 2nd order enter the 2nd division of meiosis (equation), which occurs without chromosome reduplication and leads to the formation of 4 spermatids (1с1n) - relatively small cells with a haploid set of DNA containing either an X or Y chromosome.

4) Formation phase consists of transforming spermatids into mature germ cells - sperm, which in the human body takes up to 20 days. The spermatid develops a tail, a mitochondrial coupling, and an acrosome. Almost all of the cell's cytoplasm disappears, with the exception of a small area called the residual body. At this stage of spermatogenesis, the cytoplasmic bridges between spermatogenic cells are broken, and the sperm are free, but they are not yet ready for fertilization.

The time required for spermatogonia A to develop into a sperm ready to enter the epididymis in humans is 65 days, but final differentiation of the sperm occurs in the epididymal duct over the next 2 weeks. Only in the area of ​​the tail of the epididymis do sperm become mature sex cells and acquire the ability to move independently and fertilize an egg.

Sustentocytes play an important role in spermatogenesis: they provide support-trophic, protective-barrier functions, phagocytose excess cytoplasm of spermatids, dead and abnormal germ cells; promote the movement of spermatogenic cells from the basement membrane to the lumen of the tubule. Sertoli cells are homologues of ovarian follicular cells, therefore special attention is paid to the synthetic and secretory function of these cells.

The following are formed in sustentocytes: androgen binding protein(ASB), which creates a high concentration of testosterone in spermatogenic cells, necessary for the normal course of spermatogenesis; inhibin, inhibiting the secretion of follicle-stimulating hormone (FSH) of the pituitary gland; activin, stimulating the secretion of FSH by the adenohypophysis; liquid medium tubules; local regulatory factors; Mullerian-inhibiting factor (in the fetus). Just like ovarian follicular cells, sustentocytes have receptors for FSH, under the influence of which the secretory function of sustentocytes is activated.

Blood-testis barrier. Spermatogenic cells that have entered meiotic division are isolated from the internal environment of the body by a blood-testis barrier, which protects them from the action of the immune system and toxic substances, since these cells are genetically different from other cells of the body, and if the barrier is violated, an autoimmune reaction may occur, accompanied by death and destruction germ cells.

The basal part of the convoluted tubule exchanges substances with the interstitium of the testicle and contains spermatogonia and preleptotene spermatocytes of the 1st order, that is, cells that are genetically identical to the somatic cells of the body. The adluminal region contains spermatocytes, spermatids and spermatozoa, which due to meiosis have become distinct from other cells of the body. When they enter the blood, the substances produced by these cells can be recognized by the body as foreign and undergo destruction - but this does not happen, because the contents of the adluminal section are isolated due to the lateral processes of sustentocytes - the main component of the blood-testicular barrier. Also, thanks to the barrier in the adluminal section of the spermatogenic epithelium, a specific hormonal environment is created with a high level of testosterone, necessary for spermatogenesis.

Components of the blood-testis barrier: 1) capillary endothelium of the somatic type in the interstitium, 2) basement membrane of the capillary, 3) layer of collagen fibers of the tubule, 4) layer of myoid cells of the tubule, 5) basement membrane of the convoluted tubule, 6) tight junctions between the processes of sustentocytes.

Leydig cells- perform an endocrine function in the testicle: they produce male sex hormones - androgens (testosterone), are homologs of interstitial cells of thekocytes in the ovary. Leydig cells are found in the interstitial tissue between the convoluted tubules of the testicle, lying singly or in clusters near the capillaries. Androgens produced by Leydig cells are necessary for normal spermatogenesis; they regulate the development and function of the accessory glands of the reproductive system; ensure the development of secondary sexual characteristics; determine libido and sexual behavior.

Cytochemical characteristics of Leydig cells. These are large, round-shaped cells with a light-colored nucleus with 1-2 nucleoli. The cytoplasm of the cells is acidophilic, contains a large number of elongated mitochondria with lamellar or tubular cristae, a highly developed aEPS, numerous peroxisomes, lysosomes, lipofuscin granules, lipid droplets, as well as Reike crystals - protein inclusions of regular geometric shape, the function of which is unclear. The main secretory product of Leydig cells, testosterone, is formed from cholesterol by the enzyme systems of the aEDS ​​and mitochondria. Leydig cells also produce small amounts of oxytocin, which stimulates the activity of smooth muscle cells in the vas deferens.

The secretory activity of glandulocytes is regulated by luteotropic hormone (LH). Large concentrations of testosterone, through a negative feedback mechanism, can inhibit the production of LH by gonadotropic cells of the adenohypophysis.

Regulation of the generative and endocrine function of the testicle.

Nervous regulation is provided by afferent centers of the cerebral cortex, subcortical nuclei and the sexual center of the hypothalamus, the neurosecretory nuclei of which acyclically secrete gonadoliberins and gonadostatins, therefore the functioning of the male reproductive system and spermatogenesis occurs smoothly, without sudden fluctuations.

Endocrine regulation: Testicular activity is under the control of the hypothalamic-pituitary system. Gonadotropin-releasing hormone, secreted in a pulse mode into the portal system of the pituitary gland, stimulates in the pituitary gland the synthesis of gonadotropic hormones - FSH and LH, which regulate the spermatogenic and endocrine functions of the testicle.

FSH enters the testicular interstitium from the blood capillaries, then diffuses through the basement membrane of the convoluted tubules and binds to membrane receptors on Sertoli cells, which leads to synthesis androgen binding protein(ASB) in these cells, as well as inhibin.

LH acts on Leydig cells, resulting in the synthesis of androgens - testosterone, part of which enters the blood, and the other part enters the convoluted tubules with the help of androgen binding protein: ASB binds testosterone and transfers testosterone to spermatogenic cells, namely to spermatocytes 1storder which have androgen receptors.

Women and men have the same negative feedback mechanism, through which the synthesis of gonadotropins is inhibited in the pituitary gland. Inhibin- hormone , which is produced by Sertoli cells, inhibits the formation of FSH in the adenohypophysis in the male body. Testosterone, through a negative feedback mechanism, reduces the production of LH. The more LH, the more testosterone – positive relationship, the more testosterone, the less LH – negative feedback. Testosterone also inhibits FSH release, but only slightly. The combination of action of testosterone and inhibin maximally suppresses the release of FSH.