精子特异性LRRC52作为调控雄性生育力分子靶标的探索性研究

阐明精子功能调控机制是诊疗男性不育、研发新型避孕药的前提。离子通道是决定精子功能的关键因子。实验室前期研究表明，Slo3是生理条件下调控精子功能最重要的K+通道，离体Slo3结合LRRC52后具有接近于精子钾电流的特征（PNAS,2011），然而LRRC52是否为精子Slo3的在体调节亚基亟待证实。申请者初步研究发现，LRRC52 亦定位于精子尾部主段，抗体可降低小鼠精子活性，提示LRRC52可能是Slo3的在体辅助亚基。依据良好的生殖生理学基础（Reprod Biol Endocrinol, 2010等）和精子膜片钳技术，申请者拟以小鼠和人精子为实验对象，分析LRRC52表达变化与精子活力变化的相关性；观察LRRC52缺失或抗体封闭对精子生理功能的影响；研究LRRC52调控精子钾电流及其活性的具体机制，以期为精子功能调控提供新靶标，而从人精子获得的结果则可为临床应用提供直接理论依据。

Clarifying the molecular mechanisms by which sperm functions are regulated is crucial for the treatment of male infertility and the development of novel contraceptives. Ion channels are critical regulators for sperm function. Previous reports from our laboratory showed that the sperm-specific Slo3 potassium channel plays a vital role in male mouse fertility, and heterologous expression of LRRC52 with Slo3 exhibits a current with features approximate to the native KSper（PNAS,2011）. However, whether LRRC52 is the auxiliary subunit of SlO3 in sperm is yet to be confirmed. Our preliminary studies have found that LRRC52 was located at principal piece of sperm tail, and LRRC52 antibody could reduce sperm activity in mice. Thus, we hypothesize that LRRC52 may be a native auxiliary subunit with functional effect on Slo3. Taking advantage of our extended research experience in reproductive physiology（Reprod Biol Endocrinol, 2010.etc) and sperm patch-clamp technique, we will analyze the correlation between the expression levels of LRRC52 and the changes of sperm motility, investigate the effects of LRRC52 gene deficit or LRRC52 antibody application on sperm function,and explore the underlying mechanisms of LRRC52 in regulating sperm activities. Taken together, we expect to provide a new target for the regulation of sperm function. Furthermore, the results obtained from human sperm in this study may offer scientific basis for future clinical applications.