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腹腔途径给予母代发育阶段的 vinclozolin——无雄激素拮抗剂作用的跨代遗传。

Vinclozolin--no transgenerational inheritance of anti-androgenic effects after maternal exposure during organogenesis via the intraperitoneal route.

机构信息

Experimental Toxicology and Ecotoxicology, BASF SE, 67056 Ludwigshafen, Germany.

出版信息

Reprod Toxicol. 2013 Jun;37:6-14. doi: 10.1016/j.reprotox.2012.12.003. Epub 2013 Jan 8.

Abstract

The goal of this study was to examine the potential transgenerational inheritance of anti-androgenic effects induced by Vinclozolin administered intraperitoneally to pregnant Wistar rats (Crl:WI[Han]). Dams were dosed with Vinclozolin at 0, 4 or 100mg/kg bw/d on gestation days 6-15. Male offspring of F1-F3 generations were bred with untreated females to yield F2-F4 offspring. No evident anti-androgenic effects were observed at 4mg/kg bw/d, but a case of hypospadias as well as delayed sexual maturation in F1 male offspring was observed as a sign of anti-androgenicity at 100mg/kg bw/d. However, F1-F3 males developed normally to sexual maturity and were able to mate and to generate healthy progeny. Sperm count, morphology and motility were not affected in F1-F4 generation male offspring. In conclusion, transgenerational inheritance of Vinclozolin's anti-androgenic effects was not evident in outbred Wistar rats.

摘要

本研究旨在探讨给予怀孕 Wistar 大鼠(Crl:WI[Han])腹腔内 Vinclozolin 后诱导的抗雄激素作用的潜在跨代遗传。在妊娠第 6-15 天,母体以 0、4 或 100mg/kg bw/d 的剂量接受 Vinclozolin 处理。F1-F3 代雄性后代与未处理的雌性交配,产生 F2-F4 代后代。在 4mg/kg bw/d 时未观察到明显的抗雄激素作用,但在 100mg/kg bw/d 时观察到 F1 雄性后代出现尿道下裂和性成熟延迟,表明存在抗雄激素作用。然而,F1-F3 代雄性发育正常,达到性成熟,能够交配并产生健康后代。F1-F4 代雄性后代的精子计数、形态和活力未受影响。总之,Vinclozolin 的抗雄激素作用在 Wistar 大鼠中没有明显的跨代遗传。

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