[Impact of flutamide on sex differentiation in rats].
OBJECTIVE
To investigate the adverse effect of flutamide on the sex differentiation of F1 generation male rats and to establish a rat model of hypospadis.


METHODS
Sixty pregnant SD rats were divided randomly into one control group and five treatment groups. Flutamide was injected subcutaneously (sc) with normal salin (NS) at a dose of 0, 4882.8, 5078.1, 5273.4, 5468.7, and 6250.0 microg/kg x d to the rats in the above groups respectively during the period of gestation day (GD) 12 to 17. The fetuses of two rats from each group were anatomized on GD18 to extract genital tubercle (GT) to make pathological sections. Meanwhile, the position of testes and the development of prostates were examined. The position of urethral opening and testes were examined on GD2, 13 and 28.


RESULTS
The incidence of hypospadias increased with the dose of flutamide (0, 29.00%, 40.00%, 63.68%, 78.72%, and 100% for the above groups respectively). The incidence of single cryptorchidism also increased with the dose of flutamide (0, 4.23%, 6.23%, 9.23%, 11.52%, and 16.28% for the above groups respectively). Flutamide led to 100% incidence of prostate agenesis,100% incidence of female-like areola of nipple, and 100% incidence of female-like anogenital distance (AGD).


CONCLUSIONS
Flutamide can cause abnormal sex differentiation and sex development and induce the experimental model of hypospaias in rats.
Li
Yan
Y
Department of Environmental Health, West China School of Public Health, Sichan University, Chengdu 610041, China.
Zhang
Hao
H
Wang
Wen-Dong
WD
Liang
Ying
Y
Wu
De-Sheng
DS
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D003456:Cryptorchidism / Q000139:chemically induced; D005260:Female; D005485:Flutamide / Q000633:toxicity*; D007021:Hypospadias / Q000139:chemically induced; D008297:Male; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012733:Sex Differentiation / Q000187:drug effects*
D000726:Androgen Antagonists; D005485:Flutamide