不孕不育是世界范围共同面对的严峻生殖健康问题，近年来在我国尤显突出。我国育龄人口中不孕不育发生率已高达10%~15%。生殖发育起始于胚胎期的性别决定，随后生殖细胞分别在睾丸和卵巢中通过减数分裂得到单倍体的精子和卵子。本实验室的研究聚焦于哺乳动物性别决定和减数分裂的遗传调控，揭示人类性别紊乱、配子发生障碍等不孕不育致病机制。基于相关研究结果开发生殖调控药物及辅助生殖相关技术，采用基因编辑技术研究人类早期胚胎发育和遗传疾病的治疗。
在大部分哺乳动物中，性别的差异都是由性染色体决定的，常染色体在雌雄个体中都是一致的。长期以来人们普遍认为只有Y染色体（SRY基因）才是男性性别决定必须的，没有Y染色体的个体都发育为雌性。然而在具有XY染色体但是表现为雌性的病人中，只有一小部分是由于SRY基因的突变导致的，这提示可能有其它的性染色体基因参与雄性性别决定。我们的研究首次在X染色体上发现了一个参与雄性性别决定的基因SDX, 该基因的敲除导致XY小鼠发生性别逆转，部分成年小鼠完全逆转为雌性，内外生殖器均发育为雌性。该研究颠覆了人们对性别决定的普遍认识，首次提出X染色体基因也是雄性性腺发育必需的，只有X和Y染色体基因共同作用才能确保个体发育为雄性。文章链接：SDX on the X chromosome is required for male sex determination | Cell Research (nature.com)
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