Genital System Although genetic gender is determined at fertilization, the early genital system is indistinguishable between the two genders in the embryonic stage. This is known as the “indifferent stage” of genital development, during which both male and female fetuses have gonads with prominent cortical and medullary regions, dual sets of genital ducts, and external genitalia that appear similar. Male sexual differentiation is an “active” process, requiring the presence of the SRY gene (gender-determining region), located on the short arm of the Y chromosome. Clinically, gender is not apparent until about the 12th week of embryonic life and depends on the elaboration of testis-determining factor and, subsequently, androgens by the male gonad. Female development is called the “basic developmental path of the human embryo,” requiring not estrogen but the absence of testosterone.
The primordial germ cells migrate from the yolk sac through the mesentery of the hindgut to the posterior body wall mesenchyme at about the 10th thoracic level, which is the initial site of the future ovary (Figs. 5.10 and 5.11). Once the germ cells reach this area, they induce proliferation of cells in the adjacent mesonephros and celomic epithelium to form a pair of genital ridges medial to the mesonephros. This occurs during the 5th week of gestation. The development of the gonad is absolutely dependent on this proliferation because these cells form a supporting aggregate of cells (the primitive sex cords) that invest the germ cells and without which the gonad would degenerate.
M¨ullerian Ducts The paramesonephric or m¨ullerian ducts form lateral to the mesonephric ducts; they grow caudally and then medially to fuse in the midline. They contact the urogenital sinus in the region of the posterior urethra at a slight thickening known as the sinusal tubercle. Subsequent sexual development is controlled by the presence or absence of testis-determining factor, encoded on the Y chromosome and elaborated by the somatic sex cord cells. Testis-determining factor causes the degeneration of the gonadal cortex and differentiation of the medullary region of the gonad into Sertoli cells.
The Sertoli cells secrete a glycoprotein known as anti-m¨ullerian hormone (AMH), which causes regression of the paramesonephric duct system in the male embryo and is the likely signal for differentiation of Leydig cells from the surrounding mesenchyme. The Leydig cells produce testosterone and, with the converting enzyme 5α-reductase, dihydrotestosterone. Testosterone is responsible for evolution of the mesonephric duct system into the vas deferens, epididymis, ejaculatory ducts, and seminal vesicle. At puberty, testosterone leads to spermatogenesis and changes in primary and secondary sex characteristics. Dihydrotestosterone triggers the development of the male external genitalia and the prostate and bulbourethral glands. In the absence of testis-determining factor, the medulla regresses, and the cortical sex cords break up into isolated cell clusters (the primordial follicles).
The germ cells differentiate into oogonia and enter the first meiotic division as primary oocytes, at which point development is arrested until puberty. In the absence of AMH, the mesonephric duct system degenerates, although in at least one-fourth of adult women, remnants may be found in the mesovarium (epoophoron, paroophoron) or along the lateral wall of the uterus or vagina (Gartner duct cyst) (24).
The paramesonephric duct system subsequently develops. The inferior fused portion becomes the uterovaginal canal, which later becomes the epithelium and glands of the uterus and the upper vagina. The endometrial stroma and myometrium differentiate from surrounding mesenchyme.
Figure 5.10 The comparative changes of the female and male during early embryonic development.