Yuan Cong, Zhang Yingying, Liu Yan, Wang Song, Wang Zaizhao
College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling, Shaanxi 712100 China.
College of Animal Science and Technology, Northwest A&F University, Shaanxi Key Laboratory of Molecular Biology for Agriculture, Yangling, Shaanxi 712100 China.
Chemosphere. 2017 Mar;171:355-361. doi: 10.1016/j.chemosphere.2016.12.098. Epub 2016 Dec 21.
Inevitable BPA exposure resulted in disturbance of DNA methylation status and our published study suspected that BPA has the potentiality to disturb DNA demethylation and GSH production in Gobiocypris rarus testes. To confirm this conjecture, several experiments were carried out in the present study. Adult male G. rarus was exposed to 1, 15 and 225 μg L (nominal concentration) BPA for two weeks. The levels of 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC), glutathione (GSH), and enzyme levels for DNA methylation and GSH synthesis in the testes were detected. Meanwhile, the contents of substrates for GSH synthesis were measured. Furthermore, the transcriptional changes of the studied genes were examined. Results indicated that 1-225 μg L BPA caused decrease of testicular ten-eleven translocation proteins (TETs) with more obvious effects at low concentrations. Moreover, all concentrations of BPA resulted in decrease of 5hmC levels while only 225 μg L BPA resulted in significant increase of 5mC. In addition, all treatments resulted in significant decrease of GSH and the replenishment of GSH might be mainly accomplished by circular synthesis. These results indicated that BPA exposure inhibited TETs-mediated DNA demethylation and the declined DNA demethylation mediated by TETs may result in DNA hypermethylation at 225 μg L BPA. In addition, the changes of DNA methylation status were irrelevant with GSH levels.
不可避免的双酚A暴露导致DNA甲基化状态紊乱，我们已发表的研究怀疑双酚A有可能干扰稀有鮈鲫睾丸中的DNA去甲基化和谷胱甘肽（GSH）生成。为证实这一推测，本研究开展了多项实验。成年雄性稀有鮈鲫暴露于1、15和225μg/L（标称浓度）的双酚A中两周。检测了睾丸中5-甲基胞嘧啶（5mC）、5-羟甲基胞嘧啶（5hmC）、谷胱甘肽（GSH）的水平以及DNA甲基化和GSH合成的酶水平。同时，测定了GSH合成底物的含量。此外，还检测了所研究基因的转录变化。结果表明，1-225μg/L的双酚A导致睾丸中十一-易位蛋白（TETs）减少，低浓度时影响更明显。而且，所有浓度的双酚A均导致5hmC水平降低，而只有225μg/L的双酚A导致5mC显著增加。此外，所有处理均导致GSH显著降低，GSH的补充可能主要通过循环合成来完成。这些结果表明，双酚A暴露抑制了TETs介导的DNA去甲基化，在225μg/L双酚A时，TETs介导的DNA去甲基化下降可能导致DNA高甲基化。此外，DNA甲基化状态的变化与GSH水平无关。
