胚胎植入和蜕膜发育是决定妊娠成功的关键环节，这个发生在子宫中的连续生理过程受到了卵巢雌孕激素的精密调控。妊娠过程中，卵巢雌孕激素的分泌不仅受到下丘脑-垂体的调控，同时还受到胎儿或胎盘来源的妊娠识别信号调节。而子宫组织除受到这些激素的调控外，对卵巢甾体激素合成的功能是否有反馈调节还不清楚。申请人在前期研究中已经证实Notch信号的下游核心转录因子Rbpj通过不同分子机制分别在子宫接受态建立和蜕膜分化中发挥关键作用。本项目拟进一步研究：（1）在正常妊娠及多种应激环境下，子宫Notch受体所介导的信号是否参与妊娠的建立和维持过程；（2）利用Notch通路的转基因小鼠证实妊娠过程中子宫来源的信号是否参与对卵巢孕激素合成的调控及其分子机制。本研究旨在全面揭示子宫Notch受体信号对妊娠维持的关键作用，为临床上子宫因素造成的不孕提供新的理论指导。

Embryo implantation and decidual differentiation are two critical events occurred in the uterus for the pregnancy success, which are mainly under the control of ovarian estrogen and progesterone. Notch signaling was evolutionarily conserved pathway to regulate many physiological and developmental functions. During the pregnancy, both the hypothalamus-pituitary axis and fetal originated signaling determine the synthesis of ovarian hormones. Though the uterus was mainly influenced by the ovarian hormones, it remains elusive whether the uterine signaling could feedback regulate the ovarian hormone production. In the previous study, we have demonstrated that the uterine Rbpj, as the core transcription factor in the Notch pathway, regulate the uterus receptivity and decidualization through the different mechanisms. In the present research, we intend to further investigate: (1) the physiological function of uterine Notch2 for pregnancy success under the normal or environmental stress conditions; (2) whether the uterine signaling is involved in the regulation of ovarian hormone production by utilizing the multiple Notch pathway mouse models and the underlying molecular mechanism. This study aims to comprehensively reveal the function of uterine Notch signaling during pregnancy establishment and maintenance and would give some clues for the theoretical basis to the infertility.