REPRODUCTIVE EMBRYOLOGY

Part of “CHAPTER 90 – NORMAL AND ABNORMAL SEXUAL DIFFERENTIATION AND DEVELOPMENT“

Early in ontogeny, the gonads of both sexes are indifferent and bipotential. Large primordial germ cells are visible in the fourth week among the endodermal cells of the wall of the yolk sac near the origin of the allantois. In the fifth week, these germ cells migrate by ameboid movement along the dorsal mesentery of the hindgut to the gonadal ridges (Fig. 90-9). During the sixth week, the primordial germ cells migrate into the underlying mesenchyme and become incorporated in the primary sex cords (Fig. 90-10, see also Fig. 90-9).

FIGURE 90-9. A, Drawing of 5-week embryo depicting migration of primordial germ cells. B, Three-dimensional sketch of caudal region of 5-week embryo, showing location and extent of the gonadal ridges on medial aspect of urogenital ridges. C, Transverse section, showing anlage of adrenal (suprarenal) glands, gonadal ridges, and migration of primordial germ cells. D, Transverse section through 6-week embryo, showing primary sex cords and developing müllerian (paramesonephric) ducts. E, Similar transverse section at later stage, showing the indifferent gonads and müllerian and wolffian (mesonephric) ducts. (From Moore KL. The developing human: clinically oriented embryology, 3rd ed. Philadelphia: WB Saunders, 1982:271.)

FIGURE 90-10. Schematic sections illustrating differentiation of indifferent gonads into testes or ovaries. A, At 6 weeks, indifferent gonads are composed of outer cortex and inner medulla. B, By 7 weeks, testes begin to develop under the influence of the testes-determining factor on the Y chromosome. Primary sex cords have become seminiferous cords, and they are separated from the surface epithelium by the tunica albuginea. C, By 12 weeks, ovaries begin to develop in the absence of any influence from a Y chromosome. Cortical cords have extended from surface epithelium, displacing the primary sex cords centrally into the mesovarium, where they form rudimentary rete ovarii. D, Testis at 20 weeks has a well-developed rete testis and seminiferous tubules derived from the seminiferous cords. An efferent ductule has developed from a wolffian tubule, and the wolffian duct has become the duct of the epididymis. E, Ovary at 20 weeks contains primordial follicles formed from cortical cords. Rete ovarii derived from primary sex cords and wolffian tubule and duct are regressing. F, Section of seminiferous tubule from 20-week fetus. No lumen is present at this stage, and the seminiferous epithelium is composed of two kinds of cells. G, Section of ovarian cortex of 20-week fetus showing three primordial follicles. (From Moore KL. The developing human: clinically oriented embryology, 3rd ed. Philadelphia: WB Saunders, 1982:271.)

Divergent development begins at ˜40 days of gestation. With the development of the gonad, controlled by a gene or genes regulating testicular differentiation, the translation of gonadal sex into phenotypic sex follows predictably as a function of the type of gonad formed.

In males, gonaductal differentiation depends on at least two substances secreted by the fetal testes (Fig. 90-11 and Fig. 90-12). The first, testosterone, is produced by the Leydig cells. This hormone stabilizes the wolffian ducts to stimulate the growth and development of the epididymis, vasa deferentia, and seminal vesicles. The second, AMH, is a glycoprotein secreted by the Sertoli cells that acts locally to cause nearly complete regression of the müllerian ducts by 8 weeks of fetal age, before the secretion

of testosterone and the stimulation of the wolffian ducts.39 Studies have established that AMH is similar structurally to transforming growth factor-β (TGF-β) and to ovarian inhibin.39,40 and 41 The structural locus has been localized to the short arm of chromosome 19.42 The receptor for AMH, a serine-threonine kinase with a single transmembrane domain, is expressed in the region around the fetal müllerian duct and in Sertoli and granulosa cells.43,44

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