Differentiation of the Genital Ducts Is Determined by Hormones

During the indifferent stage, the primordial genital ducts are the paired mesonephric (wolffian) ducts and the paired paramesonephric (müllerian) ducts. In the normal male fetus, the wolffian ducts give rise to the epididymis, vas deferens, seminal vesicles, and ejaculatory ducts, while the müllerian ducts become vestigial. In the normal female fetus, the müllerian ducts fuse at the midline and develop into the oviducts, uterus, cervix, and upper portion of the vagina, while the wolffian ducts regress (Fig. 39.9). The mesonephros is the embryonic kidney.

The fetal testes differentiate between weeks 6 and 8 of gestation. Leydig cells, either autonomously or under regulation by hCG, start producing testosterone. Sertoli cells produce two nonsteroidal compounds. One is the antimül-lerian hormone (AMH), also known as müllerian inhibiting substance, a large glycoprotein with a sequence homologous to inhibin and transforming growth factor (P, which inhibits cell division of the müllerian ducts. The second is androgen-binding protein (ABP), which binds testosterone. Peak production of these compounds occurs between weeks 9 and 12, coinciding with the time of differentiation of the internal genitalia along the male line. The ovary, which differentiates later, does not produce hormones and has a passive role.

The primordial external genitalia include the genital tubercle, genital swellings, urethral folds, and urogenital sinus. Differentiation of the external genitalia also occurs between weeks 8 and 12 and is determined by the presence or absence of male sex hormones. Differentiation along the male line requires active 5a-reductase, the enzyme that converts testosterone to DHT. Without DHT, regardless of the genetic, gonadal, or hormonal sex, the external genitalia develop along the female pattern. The structures that develop from the primordial structures are illustrated in Figure 39.10, and a summary of sexual differentiation during fetal life is shown in Figure 39.11. Andro-gen-dependent differentiation occurs only during fetal life and is thereafter irreversible. However, the exposure of females to high androgens either before or after birth can cause clitoral hypertrophy. Testicular descent into the scrotum, which occurs during the third trimester, is also controlled by androgens.

Gonad

Gonad

Mesonephros Müllerian duct Wolffian duct

Urogenital sinus

Indifferent stage

Indifferent stage

Fallopian tube

Fallopian tube

Female Uro Sinus

Vagina

Female

Vagina

Female

Mesonephros Müllerian duct Wolffian duct

Urogenital sinus

Testis

Testis

Epididymis Vas deferens Seminal vesicle Prostate

Bulbourethral gland

Male

Male

Epididymis Vas deferens Seminal vesicle Prostate

Bulbourethral gland

Differentiation of the internal genitalia and the primordial ducts.

(Modified from George FW, Wilson JD. Embryology of the urinary tract. In: Walsh PC, Retik AB, Stamey TA, et al., eds. Campbell's Urology. 6th Ed. Philadelphia: WB Saunders, 1992;.1496.)

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