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

Abstract

OBJECTIVE: To phenotype transcriptomically M1 macrophages (Mvarphi1) and M2 macrophages (Mvarphi2) 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): Mvarphi1, Mvarphi2, 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 Mvarphi1 and Mvarphi2 in women with and without endometriosis and in Mvarphi1 versus Mvarphi2 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 Mvarphi1 were higher in the endometriosis group versus controls. Statistical transcriptomic analysis was performed only in Mvarphi1 and Mvarphi2 populations due to larger sample sizes. Bioinformatic analyses revealed that in women with endometriosis, endometrial Mvarphi1 are more proinflammatory than controls and that Mvarphi2 paradoxically have a proinflammatory phenotype. CONCLUSION(S): As Mvarphi are phenotypically plastic and their polarization state depends on their microenvironment, the altered endometrial environment in women with endometriosis may promote endometrial Mvarphi2 polarization and an Mvarphi1 proinflammatory phenotype. Moreover, aberrant phenotypes of Mvarphi 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.