磷脂酰丝氨酸调控内膜Mφ异常分化导致子宫内膜异位症蜕膜化障碍的机制研究

子宫内膜异位症（EMs）患者的子宫内膜间质细胞蜕膜化能力受损，与EMs不孕患者胚胎着床失败密切相关。我们前期研究证实，EMs患者子宫内膜中CD11c(high)巨噬细胞（Mφ）比例降低，与蜕膜化进程抑制有关；进一步发现，EMs患者来源低自噬子宫内膜间质细胞中磷脂酰丝氨酸（PS）含量减少，是导致CD11c(high)Mφ减少的关键因素。由此我们推测：EMs患者子宫内膜中PS含量减少，影响子宫内膜CD11c(high)Mφ分化，进而抑制间质细胞蜕膜化，是导致EMs患者胚胎不能成功着床的重要原因。本项目拟在前期工作基础上，从临床样本、磷脂酰丝氨酸合成酶1敲除动物模型和细胞水平等层面研究子宫内膜间质细胞PS水平调控内膜Mφ分化，影响子宫内膜蜕膜化的作用和机制，并进一步探讨该过程在EMs患者和动物模型中的变化和作用，以期阐明临床EMs患者行辅助生殖治疗时胚胎着床率降低的原因，并提出可能的干预新策略。

It was confirmed that women with endometriosis exerted impaired endometrial decidualization and failed embryo implantation. However, the underlying mechanism remains elusive. Our previous studies have showed that the proportion of endometrial CD11c(high) macrophage (Mφ) was decreased in endometriosis, and inhibited the endometrial stromal cells (ESCs) decidualization. In addition, the lower level of autophagy in ESCs from endometriosis patients displayed decreased content of phosphatidylserine (PS), which impaired the differentiation of CD11c(high) Mφ in ESC-Mφ co-culture system in vitro. According to our previous study, we hypothesized that aberrantly decreased level of PS in the endometrium of endometriosis patients might inhibit CD11c(high) Mφ differentiation, thus leading to the impaired endometrial stromal cells decidualization and failed embryo implantation. Therefore, we proposed to explore the role of autophagy-regulated PS content in the differentiation of endometrial Mφ, and the molecular mechanisms of endometrial stromal cells decidualization mediated by CD11c(high) Mφ in vitro and in a uterine stromal cell-specific Ptdss1（Phosphatidylserine synthase 1）knockout mouse model, as well as in endometriosis patients and mouse model. These findings have implications for future therapeutic strategies specifically targeting the implantation failure in assisted reproduction technology of endometriosis.