The antiandrogen flutamide perturbs inguinoscrotal testicular descent in the rat and suggests a link with mammary development

Abstract

Aim: Inadequate androgen activity is a likely cause of cryptorchidism in humans, affecting inguinoscrotal testicular descent. Flutamide, a nonsteroidal antiandrogen, produces cryptorchidism in rats. We aimed to determine the anatomical and histologic effects of flutamide.

Methods: Time-mated Sprague-Dawley female rats were injected subcutaneously with flutamide (75 mg/kg in sunflower oil) on days 16 to 19 of pregnancy. Embryonic (E) and postnatal (P) male offspring were collected (E16, E19, P0, P2, P4, P8) in control and flutamide-treated groups (n = 5-10). Samples were fixed in 4% paraformaldehyde. Five-micrometer-thick sections were prepared for hematoxylin and eosin, trichrome and immunohistochemical stains (Desmin, TuJ1, Ki67). This identified muscle and neural cells and areas of cell proliferation.

Results: Postnatally, the gubernaculum in flutamide-treated rats had more mesenchyme and muscle than controls. Gubernacular eversion failed, and mammary tissue persisted around the gubernaculum in flutamide-treated rats. Flutamide had no effect on embryonic gubernacular anatomy and histology.

Conclusions: Prenatal androgens altered postnatal gubernacular anatomy and histology in the postnatal period. Our findings indicate that the failure of gubernacular differentiation and migration may be because of the ongoing presence of mammary tissue in the region of the external inguinal ring.