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Sexual Differentiation in the Neonate: Rodent vs. Primate Comparisons

Merck, Sharpe, and Dohme Research Laboratories Department of Safety Assessment WP-45 West Point, PA 19486

There are some similarities and differences in the process of sexual differentiation during development in rodents and primates. The most obvious difference is in the timing of the critical periods for morphogenesis of the reproductive tract and sexual differentiation of the central nervous system (CNS). In primates these events occur late in the first trimester while in rodents they occur in the perinatal period.

The gonadal hormones involved in morphogenesis of the male reproductive tract are identical for all mammalian species studied. Testosterone is the androgen that induces differentiation of the seminal vesicles, vas deferens, and epididymis, while dihydrotestosterone (DHT) promotes differentiation of the external genitalia, urethra, and prostate.

Estrogens, derived from aromatization of testosterone, are the proximal determinants of male sexual differentiation of the CNS in rodents. In nonhuman primates, however, a nonaromatizable androgen, DHT, produces the same effect as testosterone on sexually differentiated behaviors in female offspring. Studies of male patients with 5-reductase deficiency have suggested that maturation of male gender identity and psychosexual behavior in humans is critically dependent on testosterone but not on normal levels of DHT in prenatal and prepubertal life. Gender identity does not appear to be unalterably fixed in humans until the time of puberty and even at this and later times environmental factors have a strong impact.

International Journal of Toxicology, Vol. 8, No. 5, 971-979 (1989)
DOI: 10.3109/10915818909018059


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