Bisphenol A induced male germ cell apoptosis via IFNβ-XAF1-XIAP pathway in adult mice
Bisphenol A induced male germ cell apoptosis via IFNβ-XAF1-XIAP pathway in adult mice
复制标题
双酚 A 通过 IFN beta-XAF1-XIAP 途径诱导成年小鼠雄性生殖细胞凋亡
DOI：
10.1016/j.taap.2018.07.009
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发表时间：
2018-09-15
影响因子：
3.8
通讯作者：
Liu, Jin-yi
中科院分区：
文献类型：
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作者：
Jiang, Xiao;Yin, Li;Liu, Jin-yi
双酚A(BPA)通过作为内分泌干扰物损害男性的生育能力。然而，双酚A引起生殖毒性的机制还没有完全阐明。在这里，我们探讨了一种新的促凋亡分子XAF1在双酚A诱导的精子异常发生中的作用以及SPA诱导的XAF1的转录调控机制。双酚A可诱导生殖细胞过度凋亡，从而对精子发生产生不利影响。双酚A暴露后，生殖细胞中XAF1表达上调，参与了细胞凋亡途径。此外，BPA暴露后XIAP和XAF1的表达水平呈负相关。下调XAF1表达可部分抑制GC-2细胞的凋亡，抑制caspase3的激活，提高BPA诱导的XIAP的表达。此外，在体外和体内，BPA暴露后，干扰素β的表达水平都显著上调，并且这些水平与XAF1的表达呈正相关。此外，干扰素β基因敲除降低了BPA处理的GC-2细胞中XAF1的表达，增加了XIAP的表达。综上所述，这些数据表明，SPA通过干扰素β-XAF1-XIAP途径触发小鼠雄性生殖细胞凋亡，这可能是BPA诱导睾丸毒性的原因之一。
Bisphenol A (BPA) impairs male fertility by acting as an endocrine disruptor. However, the mechanisms by which BPA cause reproductive toxicity are not fully elucidated. Here, we explored the role of XAF1, a novel proapoptosis molecule, in BPA-induced abnormal spermatogenesis and the transcriptional regulation mechanism of SPA-induced XAF1. BPA exposure detrimentally impacted spermatogenesis by inducing excessive germ cell apoptosis. XAF1 was upregulated in germ cells after BPA exposure, which was involved in the apoptosis pathway. In addition, the expression levels of XIAP and XAF1 were inversely correlated after BPA exposure. Knockdown of XAF1 expression partially inhibited the apoptosis of GC-2 cells, suppressed the activation of caspase 3 and improved the BPA-induced XIAP expression. Moreover, IFN beta expression levels were significantly upregulated after BPA exposure both in vitro and in vivo, and these levels were positively related to the expression of XAF1. Furthermore, IFN beta knockdown reduced the expression of XAF1 and increased the expression of XIAP in BPA-treated GC-2 cells. Together, these data indicated that SPA triggers male germ cell apoptosis in mice via the IFN beta-XAF1-XIAP pathway, which may contribute to BPA-induced testis toxicity.