雌雄减数分裂交叉重组差异的分子基础

Meiosis is the foundation of spermatogenesis and oogenesis, and crossover is the key issue of meiosis. Impaired meiosis crossover is the leading cause of gametogenesis defects and the subsequent infertility, and it can also results in genetic disorder or birth defects. The crossover, in many species, is distinct between males and females. For instance, the crossover frequency in females (humans or mice) is much higher than that in males. But little is known about the mechanism underlying the differences between male and female crossovers, and systematic investigations are still lacking on this issue. The proposed project aims to perform parallel comparative investigations on crossovers differences between male and female mice. The investigations involve comparative analysis on DNA methylation, transcripteome and histone modifications to reveal the molecular basis of the genetic and epigenetic differences between male and female meiosis. We will also construct gene knockout mouse models, by analyzing the phenotypes, certain key genes are to be found in differential regulation in male and female crossovers. The abovementioned investigations will shed light on the molecular basis of the differences between male and female crossovers, and provide theoretical and practical support for the diagnosis and treatment of meiosis defects-related infertility, thus enhancing the preservation of human fertility.

减数分裂是精子和卵子形成的基础，而交叉重组是减数分裂的核心事件。交叉重组异常是导致配子发生障碍进而引起不孕不育的常见原因，也是导致出生缺陷以及多种遗传性疾病的重要因素。在多数生物中，交叉重组在雌雄两性之间存在极大的差异性。例如，人和小鼠雌性减数分裂交叉重组水平要远高于雄性。但是对引起雌雄差异性的机制还知之甚少，目前还鲜有这方面的系统性研究。本项目将针对减数分裂交叉重组在雌雄小鼠之间的差异进行全面系统的比较性研究。本项目主要通过转录组，DNA甲基化组，并且利用特异性的组蛋白修饰抗体结合免疫荧光技术，分析雌雄小鼠减数分裂细胞在遗传学和表观遗传学水平的差异；制备基因敲除小鼠并进行表型分析，揭示关键基因在雌雄减数分裂中的功能差异；最终初步阐明雌雄减数分裂交叉重组差异的分子基础。该项目的完成将为提高减数分裂异常引发的不孕不育的精准诊断和治疗，为人类生殖健康的改善提供理论基础和技术支持。

减数分裂是精子和卵子形成的基础，而交叉重组是减数分裂的核心事件。交叉重组异常是导致配子发生障碍进而引起不孕不育的常见原因，也是导致出生缺陷以及多种遗传性疾病的重要因素。在多数生物中，交叉重组在雌雄两性之间存在极大的差异性，本项目针对减数分裂交叉重组在雌雄小鼠之间的差异进行了全面系统的比较性研究。本项目主要通过转录组分析鉴定了雄性减数分裂和雌性减数分裂差异表达基因，并且利用特异性的组蛋白修饰抗体结合免疫荧光技术，系统分析了雌雄小鼠减数分裂细胞在遗传学和表观遗传学水平的差异；基于上述结果制备MEIOK21基因敲除小鼠并进行表型分析和机制解析，初步揭示MEIOK21在雌雄减数分裂中的功能差异。本项目的系统解析了雌雄减数分裂重组差异的分子基础，为人类生殖健康的改善提供理论基础和技术支持。