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VINCLOZOLIN (V) TREATMENT INDUCES REPRODUCTIVE MALFORMATIONS AND INFERTILITY IN F1 MALE RATS WHEN ADMINISTERED DURING SEXUAL BUT NOT GONADAL DIFFERENTIATION. THE EFFECTS ARE NOT TRANSMITTED TO THE SUBSEQUENT GENERATIONS.
Citation:
FURR, J. R. AND L. E. GRAY. VINCLOZOLIN (V) TREATMENT INDUCES REPRODUCTIVE MALFORMATIONS AND INFERTILITY IN F1 MALE RATS WHEN ADMINISTERED DURING SEXUAL BUT NOT GONADAL DIFFERENTIATION. THE EFFECTS ARE NOT TRANSMITTED TO THE SUBSEQUENT GENERATIONS. . Presented at 2009 SOT Annual Meeting, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
This work demonstrates that administration of vinclozolin via a relevant route of administration during fetal gonadal differentiation does not induce hertiable reproductive effects in male rats
Description:
V produces adverse reproductive effects in male rats when administered during sexual differentiation by acting as an androgen-antagonist. It was recently reported that four generations of SD rats, derived from dams dosed via ip injection GD8-15 with 100 mg V/kg/day, displayed prostate, testis, kidney and immune pathologies and infertility. The authors also reported that these abnormalities were transmitted via epigenetic mechanisms. Our study was designed to determine if such effects could he induced by oral treatment with V. Two groups of SD rats were dosed with 100 mg Vikg/d during either gonadal (GDS- 15) or sexual (GD13-17) differentiation. Vehicle controls were dosed GDS-17. GD 13- 17 V treatment demasculinized F 1 male rats, however none of the effects were transmitted to the F2 or F3 generations. In F1 males, GD13-17 V treatment reduced anogenital distance at birth and androgen-dependent tissue weights, and induced female-like nipples, undescended testes, histopathological lesions in the testis, hypospadias and infertility. The effects of V on AGD, nipple and fertility were not transmitted to the F2 generation. In contrast, GD8-15 V treatment did not reduce F1 or F2 fertility, induce reproductive tract malformations, or reduce epididymal sperm numbers in the F1 generation. F3 males will be examined at middle age and the histology of the testes and other organs measured in the males from all generations to determine if V treatment induced affects on these measures. In summary, oral V treatment during gonadal differentiation did not affect reproductive morphology, sperm numbers or the fertility in the F1 or F2 generations. In contrast, clear adverse reproductive effects were seen in the F1 group exposed to V during androgen-dependent sexual differentiation, however these effects were not transmitted to the F2 generation. This abstract does not necessarily reflect US EPA policy.