Fig. 8.

Monocyte-derived macrophages are guardians of the peritoneal cavity in mice with induced endometriosis. Created with https://biorender.com/. Lesion-resident macrophages are a heterogenous population constituted by macrophages that have different origins; endometrial, peritoneal (LpM), and recruited monocytes that differentiate into macrophages in lesions. Wild-type mice with induced endometriosis exhibit increased monocyte recruitment and replenishment of LpM pools from monocytes. In mice where monocyte recruitment is constitutively limited (Ccr2^−/− or Ccl2^−/−), LpM and SpM pools are significantly reduced, consistent with the majority of LpM in the peritoneal cavity being embryo-derived. In these (monocytopenic) mice, more lesions develop. Mice with ontogenetically reprogrammed peritoneal cavities (embryo-derived LpM depleted using liposomal clodronate followed by a 19-d replenishment window) develop significantly fewer lesions. Collectively, these data suggest that monocyte-derived LpM protect the peritoneal cavity when challenged with ectopic endometrial tissue. We propose a putative model where endometrial macrophages promote lesion growth, while monocyte-derived macrophages (possibly monocyte-derived LpM) protect the peritoneal cavity against establishment of lesions.