cav3调控精子发生的分子机制研究

精子发生障碍是男性不育的主要病因，主要表现为无精子症或少弱精子症。鉴定调控精子发生的关键基因并揭示其分子机制具有重要的基础和临床意义。前期工作中我们发现一个雄性不育的斑马鱼突变体ja010，该突变体精原细胞分化受阻导致精子发生出现障碍，同时产生生殖细胞肿瘤。我们鉴定出ja010突变体致变基因为cav3，并发现cav3突变导致BMP信号明显下调。由此，我们提出cav3通过介导BMP信号通路调控精子发生的假说。为了证实并阐明cav3调控精子发生的分子机制，本项目将开展以下三项工作：1）具有精子发生障碍的ja010突变体的表型分析；2）致变基因的定位克隆和确定；3）cav3介导BMP信号通路调控精子发生的分子制研究。本项目从分子，细胞水平揭示cav3调控精子发生的分子机制，研究成果有利于深入理解精子发生的分子调控机制，并为临床诊断和治疗精子发生障碍提供理论基础。

Spermatogenesis disorder is the main cause of male infertility, mainly presenting azoospermia or oligospermia.Identification of key genes regulating spermatogenesis and revealing their molecular mechanisms have important basic and clinical significance.In our previous study, we found a male sterile zebrafish mutant ja010 presenting disorder of spermatogenesis and defection of spermatogonia differentiation leading to the formation of GCTs. We identified the gene responsible for ja010 is cav3 and found that Mutations in cav3 cause downregulation of BMP signaling. Therefore, we propose the hypothesis that cav3 regulates spermatogenesis by mediating BMP signaling. To reveal the molecular mechanisms of cav3 in the regulation of spermatogenesis, our work is divided into three parts: 1) the phenotype of spermatogenesis defection in ja010 mutant is identified and analyzed; 2) Positional cloning and identification of mutant gene; 3) Study on molecular mechanisms of cav3 in the regulation of spermatogenesis by mediating BMP signaling.Thus, our study will generate new knowledge on molecular mechanisms of spermatogenesis.