Environmental antiandrogens: low doses of the fungicide vinclozolin alter sexual differentiation of the male rat:

In humans and rodents, exposure to antiandrogenic chemicals during sexual differentiation can produce malformations of the reproductive tract. Perinatal administration of 100 or 200 mg vinclozolin (V) kg−1 day−1 during sexual differentiation in rats induces female-like anogenital distance (AGD), retained nipples, cleft phallus with hypospadias, suprainguinal ectopic scrota/testes, a vaginal pouch, epididymal granulomas, and small to absent sex accessory glands in male offspring. Vinclozolin is metabolized to at least two active forms, M1 and M2, that display antiandrogenic activity by binding the androgen receptor (AR). Here, we present information on the reproductive effects of oral treatment with low dosage levels of V during sexual differentiation of the male rat. Vinclozolin was administered to the dam at 0, 3.125, 6.25, 12.5, 25, 50, or 100 mg kg−1 day−1 from gestational day 14 to postnatal day 3 (the period of fetal/neonatal testicular testosterone synthesis and sexual differentiation). At doses of ...