[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). CONCLUSION: Flutamide can cause abnormal sex differentiation and sex development and induce the experimental model of hypospaias in rats.