Placental exosomes polarize human monocyte-derived macrophages to a decidual M2-like macrophage phenotype

Macrophages are abundant in uterine mucosa during the peri-implantation phase and early pregnancy. Decidual macrophages display dynamic changes alone with pregnancy progress: During the peri-implantation phase, macrophages displayed a pro-inflammatory phenotype which facilitates embryo implantation. While, In the late firster trimester and second trimester, decidual macrophages are anti-proinflammatory which are helpful to pregnancy maintenance. Alterations in the ratio of pro-inflammatory/anti-inflammatory decidual macrophages lead to abortion, preeclampsia, and preterm birth. Placenta-derived exosomes (pEXO) are critical in the immune cell modulation such as T cell apoptosis, NK activities, and T regulatory (Treg) differentiation. However, it is unknown whether placenta-derived exosomes contribute to decidual macrophage polarization during early pregnancy. Here we report that exosomes from the placenta explant stimulate M2 macrophage polarization via exosomal miRNA-30d-5p. Mechanistically, miRNA-30d-5p polarized macrophages to M2 phenotype by inhibiting HDAC9 expression. Furthermore, the conditioned medium of pEXO-treated macrophages promoted trophoblast migration and invasion. By contrast, conditioned medium impaired the ability of endothelial cell tube formation. However, pEXO-treated macrophages have no impact on T cell proliferation. Together, we demonstrated that pEXO promoted trophoblast migration and invasion, endothelial cell migration, and attenuation of endothelial cell tube formation by polarizing macrophage to decidua-like macrophage. Overall design: mRNA profiles of pEXO-treated macrophages (N=2) and Control macrophage (N=2)