Uterine-derived exosomes induce the M2 polarization of macrophages via miR-210-3p/ATP5D to promote endometriosis progression.

Abstract

AIMS: Endometriosis development is associated with peritoneal immune microenvironment abnormality; however, the specific mechanism is uncertain. We aimed to investigate the effects and underlying mechanisms of uterine cavity-derived exosomes on macrophage polarization and endometriosis progression. MATERIALS AND METHODS: Uterine cavity-derived exosomes, miR-210-3p inhibitor or siATP5D were used to treat macrophages. Then evaluated the polarization of macrophages. By co-culturing of treated macrophages with endometrial stromal cells in vitro and an endometriosis C57BL6 mouse model to assess the role of uterine-derived exosomes and macrophages in the development of endometriosis. KEY FINDINGS: Uterine cavity-derived exosomes could increase miR-210-3p expression and induce M2 macrophage polarization. Mechanistically, miR-210-3p can restrict ATP5D expression in macrophages, which leads to M2 polarization. In vivo experiments confirmed that macrophages lentivirally transduced with miR-210-3p can significantly decrease the growth and implantation of mouse endometriosis. SIGNIFICANCE: In summary, our findings suggest that exosomes derived from the uterine cavity may drive macrophages towards M2 and promote endometriosis progression via miR-210-3p/ATP5D.