男性精子活力下降会导致男性不育，但发病机制尚不清楚。piRNA 是一种在调控精子发生过程中起着重要作用的小分子非编码RNA。我们前期研究发现弱精症患者精浆中piRNA的种类和含量都明显减少，进一步研究发现弱精症患者精浆外泌体和精子中piRNA的表达量以及精子中与piRNA形成相关蛋白mitoPLD的表达量都显著下降。本项目在此基础上，系统开展mitoPLD-piR-1207/piR-2107-SEMG1信号轴调控精子活力的机制研究，拟通过敲除及过表达mitoPLD实验证实其直接影响piRNA的差异表达；通过荧光素酶报告等实验明确piR-1207和piR-2107直接靶向调控SEMG1基因，最后通过弱精症小鼠模型阐明mitoPLD-piRNA-target信号轴调控精子活力的分子机制。本项目旨在从分子调控通路角度为男性精子活力下降提供新的理论依据，为临床干预和诊治弱精症提供新的思路。

Low sperm motility is a common cause of male infertility, however, its molecular mechanism is not very clear. piRNA, a small non-coding RNA, plays an important role in the regulation of Spermatogenesis. In previous studies, we have found that the types and expression levels of piRNA were significantly downregulated in seminal plasma of asthenospermia patients. Furthermore, the amount of piR-1207/piR-2107 in exosomes of seminal plasma and mature sperm, which come from the asthenospermia patients, were significantly decreased. Meanwhile, mitoPLD, which is essential for piRNAs biogenesis, was also extremely downregulated. Based on these findings, this study will investigate the molecular mechanism of mitoPLD-piR-1207/piR-2107 -SEMG1 axis in regulation of sperm motility. By knockdown or overexpression of mitoPLD, we would confirm that the expression of piRNA can be directly regulated by mitoPLD. Then SEMG1 could be proved as a direct target of piR-1207 and piR-2107 by luciferase reporter assays. Lastly, using mouse asthenospermia models, we could further elucidate the molecular mechanisms of mitoPLD-piRNA-target axis in regulation of sperm motility. As such, this study will provide a novel strategy and theoretical basis for treatment of asthenospermia in the future from the perspective of molecular regulation pathway.