Читать книгу Handbook of Clinical Gender Medicine - Группа авторов - Страница 62

The initial signs of masculinization are an increased distance between the anus and genital structures. Circulating androgens, and conversion to dihydrotestosterone (DHT), induce genital tubercle (GT) growth. Tubularization of the urethral plate leads to formation of the urethra and is important for the development of corpus spongiosum and other penile structures. The fossa navicularis forms independently (ectodermal ingrowth is debated). Differentiation of the external genitalia starts at 8 weeks, the coronal sulcus separates the glans and penile shaft by 12 weeks, and the glandular urethra forms by 16 weeks. The prepuce is formed following ventral closure of the glans, and separation of skin folds from the glans is not complete until birth. Involved genes, proteins, and pathways are SHH, FGFs, BMPs, and androgen/androgen receptor.

The scrotum is formed by fusion of the labioscrotal folds under androgen action, leaving a visible raphe. Normal scrotal insertion of the gubernaculum testis is essential for the inguino-scrotal phase of the descensus. The posterior aspect of the testis is not normally covered by the processus vaginalis and is fixed to the scrotal skin. Between 63 and 77 days, feminization or differentiation from the masculinized form begins. The phallus does not lengthen but bends forward or caudally. Before 20 weeks, there is a slow phase of growth of the genital swellings that cover superior and lateral aspects of the clitoris. The anogenital distance does not change, but the phallic portion of the urogenital sinus remains open, and genital folds do not fuse. At 14-20 weeks, the vagina opens into the pelvic portion of the urogenital sinus and it becomes the vaginal vestibule. After fetal ovarian follicular growth (20-22 weeks), there is rapid ventral outgrowth of the perineum, the urethral and vaginal openings separate, and the urethra is brought to the surface. The clitoris becomes incorporated into the fused anterior ends of the genital folds (labia minora), which continue to grow posteriorly. Genital swellings lateral to the labia minora become the labia majora, anteriorly continuous as the mons pubis. The growth of the labia minora is greater than that of the labia majora; they are seen protruding out of the labia majora at 23-25 weeks of gestation. After 26 weeks, the labia majora have grown sufficiently to cover the labia minora [1, 2]. At midtrimester there is no difference in the distribution of androgen receptors between male and female fetuses in the external genitalia; estrogen receptors are present only in the genitalia of the female fetus. It is not known when estrogen receptors appear or what induces their appearance. Their lack may be what protects male fetuses from the effects of maternal estrogen.

Development of a bladder and urethra separate from the vagina requires the growth of a membrane from the cranial to the caudal region in the urogenital sinus. Anomalies of female embryogenesis during this process lead to a variety of clinically recognized disorders. Estrogen is responsible for the vascularity and thickness of vaginal tissue. Failure of the labia to fuse in the normal female fetus may be due in part to the lack of fetal androgen production and low 5-α reductase activity (and in part to maternal estrogen stimulation of ER-positive urethral folds), causing the labia minora to diverge laterally. There is extensive circumstantial evidence that 17β-estradiol and progesterone influence the postnatal physiology of extragenital and especially genital (vulval) skin in the human female.