人早孕期蜕膜巨噬细胞呈免疫耐受表型，参与胚胎植入和胎盘发育等妊娠过程，其分化发育异常与自发流产密切相关。我们新近研究发现子宫内膜基质细胞蜕膜化过程伴随1,6-二磷酸果糖（FBP）的富集，FBP可促进蜕膜IL-27分泌、诱导蜕膜环氧合酶（COX）-2+巨噬细胞分化，并改善自发流产小鼠模型的胚胎丢失，然而机制不明。故本项目以体外模拟母-胎界面微环境和体内动物实验为研究手段，利用细胞内感知蛋白鉴定、巨噬细胞耗竭和免疫重建等技术，研究FBP感知蛋白诱导蜕膜COX-2+巨噬细胞分化的分子机制，COX-2+巨噬细胞调节母-胎免疫耐受和滋养细胞侵袭的作用机制，及FBP代谢失常诱导蜕膜巨噬细胞功能异常致自发流产的病理机制。以期阐明子宫内膜蜕膜化进程中蜕膜巨噬细胞分化发育的免疫代谢调节机制及其异常致自发流产的机制，为完善母-胎免疫耐受理论提供新方向，为从免疫代谢角度寻找防治自发流产的新策略提供科学依据。

Human decidual macrophages (dMφ) with an immune tolerant phenotype in early pregnancy, are involved in several processes required for a successful pregnancy, including trophoblasts invasion as well as placental development. Their dysfunction is closely related to spontaneous abortion. Our recent studies have found that decidualization is accompanied by the enrichment of fructose-1,6-diphosphate (FBP). FBP can promote the secretion of IL-27 in decidua, induce COX-2+ dMφ differentiation and improve embryo loss in spontaneous abortion mice. But the exact molecular mechanism is unclear. Therefore, taking advantage of in vitro trials for imitating the microenvironment of decidua and in vivo animal experiments, the techniques of intracellular sense protein identification, macrophage depletion and immune reconstitution were used. Our study intends to investigate: the molecular mechanism of FBP sense protein on inducing decidual COX-2+ macrophage differentiation, the molecular mechanism of COX-2+ dMφ differentiation on regulating maternal-fetal immune tolerance and trophoblasts invasion; and the pathological mechanism of spontaneous abortion induced by FBP metabolic disorder-mediated dMφ dysfunction. This project will help to elucidate the immune metabolism mechanism of dMφ differentiation and development during decidualization and the mechanism of spontaneous abortion caused by dMφ dysfunction, provide a new direction for the theory of maternal-fetal immune tolerance, and provide a scientific basis for finding a new strategy to prevent spontaneous abortion from the perspective of immune metabolism.