Fig. 8

Schematic roles of Succinate from macrophage and peritoneal mesothelial cells in the progression of endometriosis by inducing inflammation and promoting ectopic growth. In the microenvironment of ectopic foci, exposure to inflammatory cytokines or contaction with ESCs obviously triggered succinate secretion from M1 polarized macrophages and PMCs, which are the main producers of succinate. Interestingly, compared with the normal endometrium, ESCs in ectopic tissues express high levels of SUCNR1. In PMCs, succinate promotes the auto-secretion of succinate and the expression of SUCNR1 in an autocrine amplification manner. In addition to promoting succinate accumulation, interactions between macrophages, mesothelial cells and ESCs in the ectopic milieu amplify the regulatory effect on cellular function via SUCNR1 signaling. Succinate promoted the survival, adhesion, invasion, and deep infiltration of ESCs via SUCNR1 signaling, leading to the formation of ectopic lesions in endometriosis. In conclusion, succinate in the ectopic milieu synergizes with polarized macrophages to exacerbate inflammation and facilitate endometriosis progress via succinate-SUCNR1-dependent mechanisms