热休克蛋白Dnajb8在精子变形中的机制研究

弱精子症多是由于精子发育异常导致的男性不育。我们前期研究发现，转录因子SOX30调控靶基因Dnajb8的表达。有意思的是，Dnajb8在不育人群精子中的表达显著下降。初步研究表明，DNAJB8蛋白在睾丸中特异表达，定位在精子鞭毛中段，但它是否参与调控精子尾部形成和雄性生育力并不清楚。为了研究DNAJB8在精子发生过程的具体作用机制，我们拟开展以下内容：1）DNAJB8的表达模式和亚细胞定位；2）DNAJB8对精子变形的生理功能；3）用免疫共沉淀联合质谱测定及蛋白组学分析等手段鉴定与DNAJB8相互作用蛋白，揭示其分子机理。基于已积累的工作基础，包括成功制作DNAJB8特异抗体和CRISPR/Cas9基因敲除鼠，本课题将通过详细阐述DNAJB8在睾丸中的蛋白功能，为临床弱精子症的发病原因提供新的科学见解。

Asthenozoospermia is a major cause of male infertility caused by spermiogenesis defect. We recently found that the expression of Dnajb8 was regulated by transcription factor SOX30. Interestingly, DNAJB8 expression was significantly reduced in sperm in infertile men. DNAJB8 is specifically expressed in testis and localized in the middle piece of the sperm tail. However, its precise role in sperm tail formation and male fertility remains to be identified. In order to determine the role and mechanism of DNAJB8 in spermatogenesis, we carry out the following study: 1) The expression and subcellular localization of DNAJB8; 2) Physiological function of DNAJB8 in spermiogenesis; 3) Identification of DNAJB8 interacting proteins by immunoprecipitation combined with mass spectrometry and proteomic analysis and revealing its molecular mechanism in spermatogenesis. Based on the work from DNAJB8 specifically antibody and gene knockout mice by CRISPR/Cas9, the function of DNAJB8 protein in testis is analyzed, which provides new insights for understanding the pathogenesis of asthenozoospermia.