宫腔粘连（IUA）是困扰不孕女性的重要疾病，发病机制尚不清楚，目前临床治疗效果不理想。课题组已证实经血干细胞移植能有效修复IUA。经血干细胞源于子宫内膜干细胞，但它在内膜损伤修复中的作用有待阐明。前期研究发现IUA患者子宫菌群构成显著改变，并且菌群代谢产物-短链脂肪酸的宫腔浓度显著降低，体外实验表明短链脂肪酸-丁酸钠促进经血干细胞的增殖，NEDD4-2表达上调，SMAD3表达下调，提示子宫内膜菌群调控经血干细胞增殖可能在内膜损伤后的修复过程中具有重要作用。本项目拟采用内膜类器官、细胞实验和体外实验探讨：1）短链脂肪酸调节的干细胞功能在子宫内膜损伤修复中的关键作用；2）短链脂肪酸对经血干细胞NEDD4-2表达的影响；3）NEDD4-2/SMAD3信号通路在菌群代谢产物调控经血干细胞功能中的作用机制。研究有助于理解菌群调控干细胞功能在宫腔粘连病理过程中的作用机制，并为预防粘连提供新的技术手段。

The etiology of intrauterine adhesions (IUA), a leading cause of female infertility, remains unclear. Current clinical treatments for severe IUA showed poor results. We have proved that autologous menstrual blood-derived stromal stem cells (MenSCs) transplantation was beneficial for IUA patients. MenSCs is composed of shedding endometrial stem cells during menstruation, whose function in endometrial recovery after damage needs clarification. Previously, significantly changed composition of endometrial microbiota as well as reduced microbiota metabolite-SCFA were found in IUA patients. Stimulation with sodium butyrate (NaB), one kind of SCFA, promoted the proliferation of MenSCs in vitro. Furthermore, the expression of NEDD4-2 was enhanced while its substrate SMAD3 was reduced. These results indicated that endometrial microbiota regulated expansion of MenSCs took part in endometial restoration. In this project, through using endometrial organoid, MenSCs and in vitro assays, we will investigate: 1) the key role of endometrial microbiota regulated endometrial stem cells proliferation in endometrial recovery after damage, 2) the effects of SCFA on regulating NEDD4-2/SMAD3 pathway of MenSCs, 3) the molecular mechanism of NEDD4-2/SMAD3 pathway in regulation of MenSCs. Our work will help understanding endometrial microbiota regulated endometrial stem cell function in the pathogenesis of IUA, and providing new choice for prevention of IUA and its recurrence.