BKCa对cAMP诱导的子宫内膜蜕膜化的作用机制研究

Decidulization is crucial for the establishment and maintenance of pregnancy. .Though ion-exchange inside and outside cells play an important role, the regulatory mechanism is still unclear. cAMP is a key in inducing decidulization by PKA, COX2 and PGs pathway in endometrial stromal cells. BKCa, a Ca2+ activated K+ channel protein, is involved in biological regulation of cAMP pathway by binding the regulatory site of protein phosphorylation at C terminal to PKA. In our previous study, we found that the expression of BKCa reached a peak in the mid-luteal phase, and was decreased in the decidua of spontaneous abortion patients, in addition, cAMP could stimulate K+ signal in endometrial stromal cells by BKCa, which all suggested that BKCa might regulate decidulization and embryo implantation through cAMP related signaling pathways..In this study, we will use genetic technology, exogenous BKCa and regulator of key molecules in cAMP signaling pathways, and diversified mouse models，to explore the function of BKCa in decidulization induced by cAMP and find out its upstream and downstream regulatory factors，which may provide a new idea in diagnosis and treatment strategies for implantation failure and spontaneous abortion.

子宫内膜蜕膜化是妊娠建立与维持的关键，细胞内外的离子交换在其中发挥重要作用，但其调控机制尚未明确。cAMP是诱导蜕膜化的关键分子，通过PKA、COX2、PGs等形成信号通路调控蜕膜化。BKCa是大电导钙激活钾离子通道蛋白，可通过C末端的蛋白磷酸化调节位点与PKA结合，从而参与cAMP途径的生物活性调控。我们前期研究发现BKCa表达在蜕膜化形成的黄体中期达到峰值，在自然流产蜕膜中表达降低，子宫内膜基质细胞中cAMP可通过BKCa激活K+信号，提示BKCa可能通过cAMP相关信号通路调控蜕膜化和胚胎着床。因此本研究拟利用基因技术，以及外源性给予BKCa和cAMP信号通路关键分子的调节剂，结合模式动物实验，深入探讨BKCa在cAMP诱导的蜕膜化中的作用机理和上下游调控因子，为蜕膜化相关疾病如着床失败、复发性流产的防治提供新的切入点。

子宫内膜蜕膜化是妊娠建立与维持的关键，细胞内外的离子交换在其中发挥重要作用，但其调控机制尚未明确。cAMP是诱导蜕膜化的关键分子，通过PKA、COX2、PGs等形成信号通路调控蜕膜化。BKCa是大电导钙激活钾离子通道蛋白，可通过C末端的蛋白磷酸化调节位点与PKA结合，从而参与cAMP途径的生物活性调控。我们前期研究发现BKCa表达在蜕膜化形成的黄体中期达到峰值，在自然流产蜕膜中表达降低，子宫内膜基质细胞中cAMP可通过BKCa激活K+信号，提示BKCa可能通过cAMP相关信号通路调控蜕膜化和胚胎着床。本研究利用基因技术，以及外源性给予BKCa和cAMP信号通路关键分子的调节剂，结合模式动物实验，深入探讨BKCa在cAMP诱导的蜕膜化中的作用机理和上下游调控因子，为蜕膜化相关疾病如着床失败、复发性流产的防治提供新的切入点。