Bcorl1介导SUMO修饰在精子生成障碍中的作用及其可能机制

精子生成障碍是男性不育主要原因之一，也是男性生殖健康面临的最主要威胁。课题组前期基于男性不育人群，对X染色体进行外显子测序，发现BCORL1基因突变在生精障碍患者中显著富集。在小鼠中敲除该基因的同源基因Bcorl1，雄性小鼠呈现不育表型，表现为精子活力及数量减少，精子线粒体结构异常；睾丸转录组测序发现SUMO修饰关键基因Sumo2表达显著下调，推测Bcorl1可能通过介导SUMO修饰调控精子生成过程。本研究拟揭示Bcorl1在精子生成过程中的时空表达规律及发挥作用的阶段；基于已建立的不育小鼠模型，通过ChIP-seq及ChIP-qPCR等实验论证Bcorl1调控Sumo2表达的机制；应用IP-MS等实验明确Bcorl1介导SUMO修饰在精子生成过程中的调控机制。进而阐明Bcorl1在精子生成过程中的重要作用，为男性不育的治疗提供新的理论依据。

Spermatogenesis failure is one of the most important causes of male infertility, which mainly threatens male reproductive health. We found that BCORL1 mutation was significantly enriched in patients with spermatogenesis failure using exome sequencing of the X chromosome in our previous study. Bcorl1 knockout male mice were infertile with impaired sperm motility and decreased sperm counts. Moreover, sperm cells were abnormal mitochondrial structure. Testicular mRNA-seq data showed that the expression of Sumo2 was significantly reduced in Bcorl1 knockout mice, suggesting that Bcorl1 was potentially involved in SUMOylation in spermatogenesis. This project aims to reveal the spatiotemporally dynamic expression of Bcorl1 and further clarify its function involved in different stages of spermatogenesis. Based on the established Bcorl1 knockout infertile mice model, we will apply ChIP-seq and ChIP-qPCR to explore the molecular mechanism of Bcorl1 regulate Sumo2 expression in germ cells. Finally, we will demonstrate the mechanism of Bcorl1 mediated SUMOylation in spermatogenesis by IP-MS. This project will illuminate the important role of Bcorl1 in spermatogenesis, which providing new theoretical evidence for the diagnosis of male infertility.