ABSTRACT

The development of the male reproductive system is a complex process, which occurs during fetal, neonatal, prepubertal, and pubertal periods. In the initial ambisexual stage, male and female embryos are indistinguishable anatomically, having a pair of undifferentiated gonads and two sets of mesodermally derived gonoducts, the Wolffian and Mullerian ducts, within the gonadal ridge. Sexual development in rats and mice proceeds in a cranial-to-caudal direction along the ducts over a period of approximately 5 days in the latter half of gestation (Price and Ortiz, 1965). The gonadal primordia can develop into either testes or ovaries depending on the presence or absence of the Y chromosome. In the male the Wolffian ducts (WD) and in the female the Mullerian ducts are maintained, while the other set of ducts is normally destroyed. Mullerian-inhibiting substance (MIS) is secreted by Sertoli cells of the fetal testes and causes the Mullerian ducts to regress, first at the cranial end and progressing caudally (Josso et al., 1977; Donahoe et al., 1982). Transgenic female mice that inappropriately express MIS lack structures derived from the Mullerian duct, i.e., the oviduct, uterus, and upper portion of the vagina (Behringer et al., 1990), while male mice that lack a functional MIS gene develop uteri and oviductal structures in conjunction with male urogenital organs (Behringer et al.. 1994). The observation that MIS inhibited proliferation of isolated Mullerian duct mesenchyme but not epithelium in vitro (Tsuji et al., 1992) suggests the possibility that Mullerian duct mesenchyme may mediate the destructive effects of MIS on the Mullerian duct. This idea is supported by the discovery of a candidate MIS receptor, which is localized in the mesenchyme surrounding the Mullerian duct (Baarends, et al., 1994; di Clemente, et al., 1994).