Fig. 4

Macrophage polarization and aberrant nerve distribution participate in peripheral neuroinflammation and neuroangiogenesis in endometriosis. Monocytes emigrated from the blood vessels can differentiate into macrophages under different stimuli. After that, macrophages migrate into the endometriotic lesion, mediated by multiple specific molecules (such as CSF-1, CCL-2, and MCP-1) in endometriosis. Sema3A/NRP-1 regulates the polarization of macrophage phenotype and causes macrophage entrapment into the lesion simultaneously. M2 macrophages in the lesion can secrete Sema3A, NGF, and VEGF, participating in the neuroangiogenesis in endometriotic milieus. Nerve fibers in the lesion are also capable to regulate the activity of macrophages. Macrophage and nerve interaction may exacerbate neuroinflammation in endometriosis, eventually resulting in the occurrence of pain sensation