Late-gestation exogenous oestrogen inhibits testicular descent in fetal mice despite M�llerian duct regression

Abstract

Cryptorchidism in male offspring is caused by injecting oestrogen into pregnant mice. Two proposed explanations are: (1) that oestrogen interferes with the action of mullerian inhibiting substance (MIS) on testicular descent; and (2) that oestrogen preserves the mullerian duct primarily by inhibition of MIS, and that cryptorchidism is secondary to mechanical interruption of testicular descent by the mullerian duct. To test these opposing views, 5 mg oestrogen benzoate was injected into pregnant mice on day 15 and the fetuses were delivered on day 19 by caesarean section. By day 15 the embryonic mullerian duct is almost completely regressed. Controls were animals in whom no injections were made. Sham controls were animals in whom solvent alone was injected on day 14. Twenty-six experimental animals, 24 controls, and 24 sham controls were observed for macroscopic and microscopic findings. The testes were significantly cryptorchid in oestrogen-treated mice. Histological studies confirmed that the oestrogen injections were made when the mullerian duct had almost completely regressed, since only a few cystic remnants persisted. These findings suggest that oestrogen directly causes testicular nondescent. It is postulated that oestrogen inhibits MIS and that MIS plays an important role in the transabdominal descent of the testes.