Macrophages display proinflammatory phenotypes in the eutopic endometrium of women with endometriosis with relevance to an infectious etiology of the disease

Objective: To phenotype transcriptomically M1 macrophages (M phi 1) and M2 macrophages (M phi 2) in the endometrium of women with endometriosis. Design: Prospective experimental study. Setting: University research laboratory. Patient(s): Six women with endometriosis and five controls without disease, in the secretory phase of the menstrual cycle. Intervention(s): M phi 1, M phi 2, uterine natural killer, and T regulatory cells were isolated from human endometrium using a uniquely designed cell-specific fluorescence activating cell sorting panel. Transcriptome profiles were assessed by RNA high sequencing, bioinformatics, and biological pathway analyses. Main Outcomes Measure(s): Differential gene expression between M phi 1 and M phi 2 in women with and without endometriosis and in M phi 1 versus M phi 2 in each group was determined and involved different biologic and signaling pathways. Result(s): Flow cytometry analysis showed no significant differences in total numbers of leukocytes between control and endometriosis groups, although M phi 1 were higher in the endometriosis group versus controls. Statistical transcriptomic analysis was performed only in M phi 1 and M phi 2 populations due to larger sample sizes. Bioinformatic analyses revealed that in women with endometriosis, endometrial M phi 1 are more proinflammatory than controls and that M phi 2 paradoxically have a proinflammatory phenotype. Conclusion(s): As M phi are phenotypically plastic and their polarization state depends on their microenvironment, the altered endometrial environment in women with endometriosis may promote endometrial M phi 2 polarization and an M phi 1 proinflammatory phenotype. Moreover, aberrant phenotypes of M phi may contribute to abnormal gene expression of the eutopic endometrium and a proinflammatory environment in women with endometriosis relevant to the pathophysiology of the disease and compromised reproductive outcomes. (C) 2019 by American Society for Reproductive Medicine.