人类精子中H3K9ac和H4K16ac相关DNA成分及其甲基化改变在特发性男性不育症机制中的作用研究

Idiopathic male infertility is defined as the cause of male infertility unidentified, which comprises 30%-45% of male infertility. Current studies have shown that residual histone-associated DNA fragments might contain the key genes or DNA elements for early embryogenesis. Based on our formal study, we propose that the abnormalities of those key genes or DNA elements could be the potential cause of idiopathic male infertility. We have specified the components of residual nucleosome-associated DNA in human sperm in our formal study. Utilizing next generation high-throughput sequencing and MALBAC technique, this project intends to further identify the components of predominantly residual-H3K9acand H4K16ac-related DNA in human sperm, to select the important genes or DNA elements which are related to early embryogenesis and to investigate the difference of these DNA elements between sperms of idiopathic male infertility patients and normal control sperms in histone association and DNA methylation characteristics. Our study would provide epigenetic hints for the mechanism of idiopathic male infertility.

特发性男性不育症是指不明原因导致的男性不育症，约占不育症患者总数的30%-45%。现有研究表明，精子中剩余组蛋白相关的DNA片段含有与早期胚胎发育相关的关键基因或DNA成分。在此前研究的基础上，我们进一步认为这些基因或DNA成分的表观遗传学特征异常可能是特发性男性不育症的潜在病因。我们此前的研究已明确了人类精子中剩余核小体相关DNA的成分，本项目拟进一步探索人类精子中含量占优的剩余乙酰化组蛋白H3K9ac和H4K16ac相关DNA的成分，以二代高通量测序结合多重退火环状循环扩增技术（MALBAC），筛选出与人类早期胚胎发育相关的重要基因或DNA成分，并检测这些基因或DNA成分的组蛋白相关性与甲基化程度在特发性不育症患者精子与正常精子中的区别，以期为探索特发性男性不育症的发病机制提供表观遗传学层面的参考。