Cao Shan, Xu Wei, Lou Qin-Qin, Zhang Yin-Feng, Zhao Ya-Xian, Wei Wu-Ji, Qin Zhan-Fen
Nanjing University of Technology, Nanjing 210009, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Toxicol In Vitro. 2014 Apr;28(3):426-31. doi: 10.1016/j.tiv.2013.12.003. Epub 2013 Dec 21.
Progesterone-induced germinal vesicle breakdown (GVBD) of Xenopus oocytes in vitro was used to study endocrine disrupting activity of chemicals in previous studies. In this study, we investigated for the first time effects of environmental androgens on oocyte maturation and effects of anti-androgens on androgen-induced oocyte maturation, using Xenopus GVBD in vitro. Trenbolone and nandrolone, two environmental androgens, were found to induce Xenopus GVBD at low concentrations. The potential of trenbolone to induce GVBD was approximately 100-fold lower than that of testosterone, while nandrolone had a several-fold lower potential than testosterone. Our findings have aroused new concerns for effects of environmental androgens on amphibian oocyte maturation at environmentally relevant concentrations, and suggested that Xenopus GVBD can be used to test androgenic activity of suspicious environmental androgens. Androgen receptor (AR) antagonist flutamide at 10 μM only exhibited a weakly inhibitory effect on androgen-induced GVBD, while another known AR antagonist vinclozolin had no effect even at high concentrations. The results show that Xenopus GVBD is not sensitive to AR-mediated environmental anti-androgens. In contrast to flutamide and vinclozolin, methoxychlor (a weaker AR antagonist) inhibited dramatically androgen-induced GVBD, suggesting that androgen-induced Xenopus GVBD can be used to study non-AR-mediated effects of chemicals on oocyte maturation.
在以往的研究中,曾利用孕酮诱导非洲爪蟾卵母细胞在体外发生生发泡破裂(GVBD)来研究化学物质的内分泌干扰活性。在本研究中,我们首次利用非洲爪蟾体外GVBD实验,研究了环境雄激素对卵母细胞成熟的影响以及抗雄激素对雄激素诱导的卵母细胞成熟的影响。发现两种环境雄激素群勃龙和诺龙在低浓度时即可诱导非洲爪蟾GVBD。群勃龙诱导GVBD的潜力约比睾酮低100倍,而诺龙的潜力比睾酮低几倍。我们的研究结果引发了人们对环境雄激素在环境相关浓度下对两栖类卵母细胞成熟影响的新关注,并表明非洲爪蟾GVBD可用于检测可疑环境雄激素的雄激素活性。10μM的雄激素受体(AR)拮抗剂氟他胺仅对雄激素诱导的GVBD表现出微弱的抑制作用,而另一种已知的AR拮抗剂乙烯菌核利即使在高浓度下也没有作用。结果表明,非洲爪蟾GVBD对AR介导的环境抗雄激素不敏感。与氟他胺和乙烯菌核利不同,甲氧滴滴涕(一种较弱的AR拮抗剂)能显著抑制雄激素诱导的GVBD,这表明雄激素诱导的非洲爪蟾GVBD可用于研究化学物质对卵母细胞成熟的非AR介导作用。