不孕不育一直是困扰着诸多家庭的严重问题，在育龄夫妻中有10-15%面临不孕不育。精子释放障碍可以导致男性无精子症。然而精子释放过程中顶端ES连接是如何降解并移除的？泛素化依赖的蛋白酶体降解通路可能参与了这一重要的生物学过程。我们前期研究发现FBXO7在睾丸中参与E3泛素连接酶功能。缺失了FBXO7的小鼠，表现出雄性不育，精子无法释放，滞留于生精小管中，激素水平未见异常。缺失了FBXO7后ES连接蛋白ESPIN泛素化水平降低。提示着FBXO7可以作为“开关”分子调控精子释放功能。本课题拟通过分析生殖细胞和Sertoli细胞条件性基因敲除小鼠表型，揭示FBXO7缺失影响的具体环节；筛选和鉴定FBXO7参与SCF复合体E3泛素连接酶的底物及其他共作用蛋白，从而全面阐明FBXO7在精子释放过程中发挥的调控作用。

10%-15% of childbearing couples facing reproductive problem. Failure of spermiation leads to male infertility. It is remained unclear of regulating factors of apical ectoplasmic specialization (ES) during spermiation. Ubiquitin-26S proteasome system may involve in degradation of ES component. In our human testicular proteomics research, we focus on an E3 ubiquitin ligase component, FBXO7. FBXO7-null male mice were infertile and failure of spermiation, with normal hormone level. Lack of FBXO7 reduced ubiquitination of an ES protein, ESPIN. These results suggested that FBXO7 is an ‘on-off’ of spermiation by protein ubiquitination. We will phenotype conditional knockout of FBXO7 in germ cell and Sertoli cell; look for ubiquitinated substrates of FBXO7-E3 ligase; identify and verify FBXO7 binding protein network. Our study could provide an overall view of FBXO7 in regulation of spermiation.