项目名称: CHCHD10在双酚A致精子线粒体氧化磷酸化障碍中的作用及机制研究
项目编号: No.81502836
项目类型: 青年科学基金项目
立项/批准年度: 2016
项目学科: 医药、卫生
项目作者: 姜晓
作者单位: 中国人民解放军第三军医大学
项目金额: 18万元
中文摘要: BPA作为一种典型的环境内分泌干扰物具有明显的雄性生殖毒性,但其作用机制尚不清楚。本课题前期研究发现BPA可导致精子活力下降、精子线粒体形态改变以及精母细胞线粒体能量代谢障碍。进一步研究发现BPA处理后一个新的线粒体相关蛋白CHCHD10改变最为明显。文献调研证实CHCHD10与线粒体呼吸链复合酶及氧化磷酸化关系密切,提示CHCHD10基因可能在BPA致精子线粒体氧化磷酸化障碍中起重要作用。本项目拟构建CHCHD10基因稳定沉默细胞模型及BPA致雄性生殖毒性小鼠模型,评价BPA对小鼠精子氧化磷酸化通路的影响,分析CHCHD10在BPA致小鼠精子线粒体氧化磷酸化通路障碍中的作用,并初步探讨BPA对CHCHD10基因的调控机制,为下一步深入研究CHCHD10在BPA所致雄性生殖毒性中的作用及分子机制提供实验依据。
中文关键词: 双酚A;氧化磷酸化;线粒体呼吸链
英文摘要: BPA is a kind of typical environmental endocrine disruptor which has obvious male reproductive toxicity, but the mechanism is still unclear. It has been confirmed that BPA can affect sperm motility, morphology, and GC-2 cell energy metabolism. We found that CHCHD10 increased obviously both in gene and protein level in our previous study. These results suggest that CHCHD10 may play an important role in sperm mitochondrial oxidative phosphorylation. In this study, we will establish stable CHCHD10 gene silence cell model and BPA exposed models in vivo to investigate the effect and mechanism of CHCHD10 on BPA induced sperm mitochondrial oxidative phosphorylation disorders in mice. This study will provide data for exploring the mechanism of BPA induced male reproductive toxicity and the function of CHCHD in male reproductive system.
英文关键词: Bisphenol A;Oxidative phosphorylation;Mitochondrial respiratory chain