获能是正常生理条件下精子顶体反应、精卵融合及受精的必要前提，蛋白酪氨酸磷酸化水平是评价精子获能的重要指标。热体克蛋白 90（Hsp90）是一种高度保守的分子伴侣，有维持细胞功能、细胞信号调控等重要功能。我们前期研究发现，Hsp90特异性抑制剂格尔德霉素可增强蛋白酪氨酸磷酸化，提示与酪氨酸蛋白激酶家族成员Src密切相关，影响精子获能及受精，但目前其调控机制不清楚。因此本项目拟围绕Hsp90及Cdc37如何调控人精子获能期间的Src活性，开展四个层面研究：研究精子Hsp90共伴侣Cdc37的定位情况；是否存在Hsp90-Cdc37相互作用；它们有否被PKA、PKC磷酸化；如何调控Src活性从而影响磷酸化水平。旨在揭示Hsp90及Cdc37在获能过程中的作用及其调节Src活性的新机制，填补精子蛋白酪氨酸磷酸化的调控理论，为不明原因性男性不育的诊治提供新的科学依据，为开发男性避孕药物提供新策略。

Sperm capacitation is a prerequisite for acrosome reaction, sperm-egg fusion and fertilization under normal physiological conditions. Protein tyrosine phosphorylation is an important signature of sperm capacitation. Heat shock protein 90 (Hsp90) is a highly conserved molecular chaperone, which plays important roles in the maintenance of cell functions, signaling regulation and other important biological functions. In the previous study, we found that geldanamycin, a specific inhibitor of Hsp90, enhances protein tyrosine phosphorylation in human sperm, suggesting the phenomenon is closely involved in tyrosine protein kinase family member Src (Src), which affects capacitation and fertilization. However, the mechanism by which Hsp90 regulates Src in human sperm remains unclear. Therefore, this study will focus on how Hsp90 regulates the Src activity during human sperm capacitation in four perspectives: where cell division cycle protein 37 (Cdc37), Hsp90 co-chaperone protein, in human sperm locates; whether Hsp90 acts by interacting with Cdc37; whether Hsp90 and Cdc37 is phosphorylated by the kinase of PKA and PKC; and how these factors affect the Src activity leading to protein phosphorylation. This study is to clarify the roles of Hsp90 and Cdc37 and the new mechanism by which they regulate the Src activity during capacitation. This study will complement the theory relevant to the regulation of protein phosphorylation int sperm, show new scientific evidence for the diagnosis and treatment of the unexplained male infertility and provide new strategy for the development of male contraceptive drugs.