生物节律基因CRY1通过StAR调控牦牛雄激素代谢及繁殖性能的机制研究

雄激素的节律性分泌影响着动物发情、睾丸发育和精子发生等生殖过程，对动物的繁殖性能十分关键。我们前期发现生物节律基因CRY1在不同年龄段的牦牛睾丸组织中均差异表达，与其繁殖能力呈正相关；成年牦牛睾丸间质细胞中抑制CRY1表达，雄激素合成关键酶StAR表达量显著下调并伴随着雄激素分泌量明显减少。因此，我们推测CRY1通过StAR调控牦牛雄激素代谢进而影响繁殖性能，但CRY1如何调控StAR尚不清楚。本项目拟以牦牛睾丸组织、睾丸支持和间质细胞、基因敲除小鼠为研究对象，应用细胞分离培养、基因编辑、ChIP、Pull-down和Co-IP等分子生物学方法，明确CRY1与StAR的表达相关性；解析CRY1通过StAR调控雄激素合成和代谢的分子机制；阐明CRY1参与调控牦牛和小鼠雄激素代谢的生物学异同效应及其对繁殖性能的影响。这将为牦牛及其他家畜生殖生理的研究提供参考依据。

The rhythmic secretion of androgen is crucial to animal reproductive performance through regulating yak reproductive processes such as estrus, testis development and spermatogenesis. Our previously study showed the expression level of biorhythm gene CRY1 was differentially expressed in the yak testicular tissues at different ages and was up-regulated along with age, and was positively correlated with the reproductive performance. The expression of StAR was significantly down-regulated and along with the secretion of androgen significantly decreased when inhibited the expression of CRY1 in the Leydig cells from adult yak testis. Therefore, we hypothesize that CRY1 regulates the androgen metabolism of yak and affecting reproductive performance via StAR, but its mechanism remains unclear. In the present study, yak testicular tissues, Leydig and Sertoli cells and gene knockout mice will be taken as the study objects and the molecular biological methods such as primary cell culture, gene edit, ChIP, pull-down, and Co-IP will be used to clarify the expression relationship between CRY1 and StAR. And then the molecular mechanism of how CRY1 regulates androgen synthesis and metabolism via StAR will be elucidated. In addition, the biological similarities and differences and its effect on reproductive performance of CRY1 in regulating androgen metabolism between yak and mice will be elucidated. This will provide reference for the study of reproductive physiology in yak and other domestic animals.