Male reproductive toxicity of ethinylestradiol associated with 4 weeks daily dosing prior to mating in rats.

Parameters of male reproductive toxicity of ethinylestradiol were assessed by conducting a mating test, sperm assay, organ weight determination and histopathological examination. Male Sprague Dawley rats were orally administered 0.1, 0.3, 3 or 10 mg/kg/day ethinylestradiol for 4 weeks prior to mating. Body weight gain and food consumption were suppressed in all treated groups. Reproductive ability of the 3 and 10 mg/kg/day males disappeared. Slightly low copulation indices were observed in the 0.1 and 0.3 mg/kg/day groups, although fertility indices were not affected. Sperm could hardly be found in the epididymis of 3 and 10 mg/kg/day males. Sperm counts were also decreased in the other treated groups, but sperm motility was not affected. Decreased absolute and/or relative weights of testes, epididymides, prostate and seminal vesicles were observed in all treated groups along with testis, epididymis, seminal vesicle and prostate atrophy, and degenerative changes of spermatocytes, spermatids, Sertoli cells and Leydig cells. These results suggest that sperm quantification and histopathological assessment are more appropriate for assessing male reproductive toxicity of ethinylestradiol than performance of copulation and fertility tests.