持续激活型孕激素受体在小鼠子宫蜕膜化中的作用及机制研究

子宫中孕激素受体通过响应卵巢分泌的孕激素调节蜕膜化过程。在前期研究中，我们发现小鼠子宫中存在一个没有报道过的高丰度的孕激素受体变体。通过孕激素反应元件活性分析和染色质免疫共沉淀等一系列实验，我们发现该变体即使在没有孕激素存在的情况下也具有明显的转录因子活性。这是首次发现不需要孕激素的孕激素受体。我们命名为持续激活型孕激素受体（constitutively activated progesterone receptor，caPR）。利用体外模型和体内模型，我们发现敲低caPR会导致蜕膜化失败。caPR具有特殊氨基酸序列，其分子功能与孕激素受体仅有部分交叠，并不等同于孕激素受体，具有特殊活性，值得进一步探索。本项目将针对caPR在蜕膜化中的功能、作用机制和表达调节进行细致研究。本项目的实施有助于进一步了解蜕膜化的分子机理，为不孕症和妊娠相关疾病的防治提供更多线索和理论依据。

The decidualization process is regulated by ovarian progesterone via uterine progesterone receptor. Previously, we identified a novel progesterone receptor isoform of high abundancy in the mouse uterus. Through progesterone responsive element reporter assay, chromatin immunoprecipitation, as well as other experimental methods, we found that this isoform had transcription factor activity even in the absence of progesterone. Thus, we designate it as constitutively activated progesterone receptor (caPR). Using in vitro and in vivo models, we found that knockdown of caPR resulted in impaired decidualization. The caPR has a unique peptide segment, indicating that caPR may exhibit different functions compared to the classic progesterone receptor. In this study, we are going to explore in more detail the function, mechanism of action, and regulation of caPR in mouse uterus during decidualization. Our study may help to understand the molecular mechanism underlying decidualization and provide implications for the development of therapies against female infertility and pregnancy complications.