Exposure of male Albino Swiss rats to the nonsteroidal antiandrogen
flutamide during the period from
gestational day (d) 10 to birth resulted in feminisation of the external
genitalia and the suppression of
growth 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
abnormality were seen in the testes
of flutamide-treated animals, ranging from completely normal tubules with full
spermatogenesis (and the
expected frequency of the stages of spermatogenesis) to severely abnormal
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 scrotally-located
testes least; only the latter
contained normal tubules. Similarly, intra-abdominal testes were the smallest
in weight and contained the
least testosterone. By contrast, postnatal treatment of male rats with flutamide
from birth to postnatal d 14
did not impair development of the external genitalia, the process of
testicular descent or adult
spermatogenesis. These findings confirm that androgen blockade during embryonic
development interferes
with testicular descent but also demonstrate that (1) prenatal flutamide treatment
per se has a detrimental
effect on adult testis morphology but (2) the degree of abnormality of the
testes is strongly influenced by location.