Flutamide-induced cryptorchidism in the rat is associated with altered gubernacular morphology

Objectives: One of the major controversies regarding descent of the testes is whether androgenic regulation of the gubernaculum testes exists. To determine if antiandrogens can alter the development of the gubernaculum within the fetus, the following experiment was performed. Methods: Timed pregnant Sprague-Dawley rats were treated with either flutamide, dihydrotestosterone (DHT), or vehicle alone (controls) from gestational day (CD) 15 to 17. Fetal specimens were removed via cesarean section on CD 18 and 20. Serial coronal sections were obtained, and digital microscopy with computer-assisted reconstruction was used to ascertain the morphology of the three components of the gubernaculum, that is, the gubernacular cord and the mesenchymal and muscular components of the gubernacular bulb. Results: Flutamide significantly prevented and DHT significantly enhanced gubernacular cord regression compared with controls (P <0.01). Flutamide also resulted in a significant inhibition of the gubernacular bulb outgrowth, with diminution of both the mesenchymal and muscular components of the gubernacular bulb. Conclusions: These data suggest that androgens play an active role in gubernacular cord regression and gubernacular outgrowth within the fetal rodent.