THE EFFECTS OF PRENATAL AND POSTNATAL EXPOSURE TO THE NONSTEROIDAL ANTIANDROGEN FLUTAMIDE ON TESTIS DESCENT AND MORPHOLOGY IN THE ALBINO SWISS RAT

Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen fl utamide during the period from gestational day (d) 10 to birth resulte d in feminisation of the external genitalia and the suppression of gro wth of the male reproductive tract. In adulthood, testes were found to be located in diverse positions. True cryptorchidism occurred in 10% of cases, whereas 50% of testes descended to the scrotum and 40% were located in a suprainguinal ectopic region. Varying degrees of tubule a bnormality were seen in the testes of flutamide-treated animals, rangi ng from completely normal tubules with full spermatogenesis (and the e xpected frequency of the stages of spermatogenesis) to severely abnorm al tubules lined with Sertoli cells only. For each individual testis, the overall severity of tubule damage was strongly correlated with its adult location, with intra-abdominal testes worst affected and scrota lly-located testes least; only the latter contained normal tubules. Si milarly, intra-abdominal testes were the smallest in weight and contai ned the least testosterone. By contrast, postnatal treatment of male r ats with flutamide from birth to postnatal d 14 did not impair develop ment of the external genitalia, the process of testicular descent or a dult spermatogenesis. These findings confirm that androgen blockade du ring embryonic development interferes with testicular descent but also demonstrate that (1) prenatal flutamide treatment per se has a detrim ental effect on adult testis morphology but (2) the degree of abnormal ity of the testes is strongly influenced by location.