Fig. 2.

Inflammatory cells in endometriosis macrophages, MCs, and neutrophils are recruited into endometriotic lesions. After macrophage polarization, M2 macrophages secrete multiple cytokines and reduce the expression of CHUN and NFKBIA mRNA and the ratio of P-NFKBIA/NFKBIA. The latter can also promote the secretion of cytokines. Recruited MCs secrete and induce the production of cytokines, chemokines, and other mediators, resulting in angiogenesis, neurogenesis, and hypersensitivity reactions. Under the influence of a high level of E2 (estradiol), MCs degranulate and secrete a large amount of NGF. NGF upregulates NAV1.8, leading to neurogenesis and hyperalgesia. Neutrophils mainly promote the production of VEGF and IL-17α. IL-17α promotes proliferation of endometrial stromal cells (ESCs) and stimulates Gro-α, IL-8, and COX-2 secretion. In turn, the latter can promote the recruitment of neutrophils. These mediators are involved in the formation of the inflammatory microenvironment in endometriotic lesions, causing neurogenesis, angiogenesis and pain