精子功能障碍是导致男性不育的重要原因，而钙信号是调控精子功能的关键途径。特异性人精子黏附分子（SPAM1）是一种具有透明质酸酶活性、对受精过程必不可少的精子膜蛋白。研究表明SPAM1参与人精子胞内钙信号的调节，其异常与男性不育密切相关，然而具体机制尚未明确。本课题前期体外重组获得含有或不含有糖基磷脂酰肌醇（GPI）锚修饰结构域的蛋白（SPAM1或SPAM1-W），结果发现只有SPAM1能有效增强人精子胞内钙信号及顶体反应。故我们假设GPI锚修饰结构域可能是SPAM1调控钙信号的关键区域。结合蛋白重组、荧光钙信号测量和精子膜片钳等手段，本项目拟：1）进一步明确SPAM1对人精子钙信号的调控作用与功能；2）以CatSper为重点，阐明SPAM1调控钙信号的具体机制；3）探索重组SPAM1在弱精症治疗中的应用。本课题有望深化对受精过程的认识，并为精子功能障碍所致男性不育的诊断与治疗提供新思路。

Sperm dysfunction is the significant cause of male infertility, meanwhile, intracellular calcium signal regulation furtherly affects sperm function. Human sperm adhesion molecule 1 (SPAM1) with the activity of degrading hyaluronic acid is a prerequisite for fertilization. Studies have shown that SPAM1 is involved in the regulation of intracellular calcium signal in human sperm, which is closely related to male infertility. However, the pivotal mechanisms of intracellular calcium signal by the regulation of SPAM1 still remain unclear. Previously, glycosylphosphatidylinositol (GPI)-anchored protein SPAM1 and SPAM1-W protein without GPI were obtained by in vitro recombinant. Our data showed only GPI-anchored protein SPAM1 effectively enhanced the intracellular calcium concentration in human sperm by calcium imaging and SPAM1 significantly improved acrosome response in human sperm, indicating that specific GPI-anchored domain of its structure may be important for calcium regulation. In this study, combining with multiple technologies such as recombinant, calcium imaging and sperm patch clamping, this project aims to: 1) investigate the effect of SPAM1 on calcium signaling in human sperm. 2) focusing on CatSper, reveal the mechanism by which SPAM1 modulates the calcium signaling of human sperm. 3) explore the application of recombinant SPAM1 for the treatment asthenozoospermia. This research may deepen the understanding of the fertilization process and provide new thoughts for the diagnosis and treatment of male infertility caused by sperm dysfunction.