子宫内膜容受性是决定妊娠失败与否的主要原因，其关键标志是子宫内膜-蜕膜转变，但是这一过程是如何启动、维持，以及在人的生理周期中是如何被精确调控的尚不清楚。本项目拟解决“子宫内膜-蜕膜转化进程中细胞周期调节和稳态维持的分子机制是什么？”这一科学问题。利用在体基因敲除小鼠模型及体外基质细胞培养模型，结合原位杂交、免疫组化、qRT-PCR、RNA敲降等技术深入探讨：1）细胞增殖正向调节分子MCM家族和负向调节分子TOB1在小鼠子宫围植入期的动态表达模式；2）MCM家族和TOB1对小鼠子宫基质细胞蜕膜化的调节机制；3）MCM家族和TOB1在人子宫内膜不同阶段的动态表达模式；4）MCM和TOB1对人子宫基质细胞蜕膜化的调节机制；5）MCM和TOB1在人子宫内膜疾病中的表达变化及作用，力争系统研究子宫内膜-蜕膜转变中的生理和病理调节机制，为揭示不良妊娠机制及不孕不育的诊治提供理论基础。

The endometrium-decidua transformation is a key event of uterine receptivity, which determines the success of blastocyst implantation and thus the term pregnancy outcome in women. However, the mechanisms governing the initiation and maintenance of endometrium-decidua transformation during human menstrual cycle remained largely unanswered. In this proposal, we propose to address this issue exploring the molecule basis of the cell cycle regulation and the maintenance of homeostasis via employing the in vivo gene knockout mice model and in vitro stromal cell culture model in combination with in situ hybridization, immunochemistry, qRT-PCR and RNA knockdown techniques. The main reseach plan includes: 1) spatiotemporal expression patterns of cell cycle associated molecule MCM and Tob1 during the periimplantation period in mice; 2) regulatory mechanisms of MCM and Tob1 during stromal decidualization in mice; 3）dynamic expression patterns of MCM and Tob1 in different stages of human endometrium; 4) concrete regulations of MCM and Tob1 during stromal decidualization in human; 5) the different pattern and potential role of MCM and Tob1 in human endometrial diseases. This project strives for systematic study on the physiological and pathological orchestration of endometrial-decidual transformation, and will provide new idea and theoretical foundation for infertility tretements and improvememnt of ART pregnancy outcome.