Hormonal control of gubernaculum development during testis descent: Gubernaculum outgrowth in vitro requires both insulin-like factor and androgen

The gubernaculum connects the gonad to the inguinoscrotal region and is inv olved in testis descent. It rapidly develops in the male fetus, whereas dev elopment in the female fetus is lacking. Possible factors involved in guber naculum development are androgens, anti-Mullerian hormone (AMH), and insuli n-like factor (Insl3). Sexual dimorphism in gubernaculum development correl ated with the mitotic activity of cells in the gubernacular bulbs from male and female fetuses. Androgen receptor expression was restricted to the mes enchymal core of the gubernacular bulb, whereas skeletal muscle was defecte d in its outer layer. In an organ culture system devised to further study g ubernaculum development in vitro, morphology of gubernacular explants grown in the presence of testes was comparable with that of gubernacula develope d in vivo. Testicular tissue or medium containing R1881, a synthetic androg en, had a growth stimulatory effect on gubernacular explants compared with ovarian tissue or basal medium only. Moreover, Amh(-/-), Amh(+/-), and Insl 3(+/-) testes stimulated the growth of gubernacular explants to the same ex tent as control testes. Insl3(-/-) testes, however, did not produce such an activity. This study reveals an essential role for both androgen and Insl3 in the gubernaculum outgrowth during transabdominal testis descent.