维甲酸代谢调控高原鼠兔精原细胞分化的作用机制

高原鼠兔是维持青藏高原特殊生态系统的关键种。作为典型的长日照动物，高原鼠兔的繁殖调控机理研究对于揭示季节性繁殖动物的繁殖策略具有重要意义。申请人的前期工作发现，雄性高原鼠兔在短日照条件下褪黑素分泌增多，导致睾丸内睾酮和维甲酸水平的下降，引起精原细胞分化阻滞，从而进入非繁殖期。进一步的转录组学分析表明，参与维甲酸合成与降解代谢的一些关键酶类（RDHs、RALDHs、CRABPs和CYP26s等）可能涉及这一高原鼠兔精原细胞分化的节律性调控过程。为了验证这一假设，本项目拟进行如下研究：（1）维甲酸代谢酶调控高原鼠兔精原细胞分化的途径；（2）高原鼠兔睾丸内维甲酸代谢酶的上游分子调控机制。本项目的完成不仅能为高原鼠兔的种群调控和繁殖策略研究提供重要参考，还能进一步加深我们对季节性繁殖动物繁殖机理的认识，并为实现哺乳动物雄性生殖细胞发育的外界调控提供理论和技术支持。

Plateau pika (Ochotona curzoniae) plays a keystone role on ecosystem balance and biodiversity of the Qinghai-Tibetan plateau. Studies of molecular regulation in plateau pika’s reproduction have an important significance for uncovering the reproductive strategy of seasonal reproductive animals. Our previous work showed that plateau pikas released more melatonin when they were maintained under the short-day photoperiod, which had an adverse effect on the secretion of testosterone and retinoic acid in their testes, to block the spermatogonial differentiation. This arrest is the basic reason of seasonal reproduction in plateau pikas. Further transcriptomic analysis indicated that there were several crucial enzymes involved in retinoic acid synthesis and degradation, such as RDHs, RALDHs, CRABPs and CYP26s, which could participate in this rhythmic control progression. To test this hypothesis, we will perform our study as follows: (1) determining whether and how retinoic acid metabolic enzymes control spermatogonial differentiation in plateau pikas; (2) elucidating molecular mechanisms regulating retinoic acid metabolism in testis of plateau pikas. Successful completion of the proposed research will offer important reference for the population management and reproductive strategies of plateau pikas, help to understand reproductive mechanisms of seasonal breeding mammals and provide theory and technology support for external regulation strategies of male germ cell development.