Extracellular vesicle-associated microRNA-138-5p regulates embryo implantation and early pregnancy by adjusting GPR124

Abstract Background Functional embryo-maternal interactions occur during the embryo implantation and placentation. Extracellular vesicles with microRNA (miRNA) between cells have been considered of critical importance for embryo implantation and programming of human pregnancy. MicroRNA-138-5p functions as the transcriptional regulator of GPR124. However, the mechanism of microRNA-138-5p- and GPR124-regulated NLRP3 inflammasome activation remains unclear. In this study, we examine the roles of microRNA-138-5p and GPR124-regulated inflammasome in embryo implantation and early pregnancy. Methods Human decidual stromal cells were isolated from the abortus tissue, collected by curettage from missed abortion patients and normal pregnant women at 6- to 12-wk gestation, after informed consent. Transmission electron microscopy (TEM) images of isolated extracellular vesicles were obtained. NGS and microarray were performed for miRNAs analysis. The predicated target genes of the differentially expressed miRNA were analyzed to identify the target genes and their pathway. Results Isolated extracellular vesicles from decidua and decidual stromal cells were confirmed by TEM images. We demonstrated the down-regulation of miR-138-5p and the overexpression of GPR124 in spontaneous miscarriage compared to normal pregnancy. We also showed the excessive activation of NLRP3 inflammasome in spontaneous miscarriage compared to normal pregnancy. Conclusions Here we newly demonstrate that the miR-138-5p and GPR124-regulated NLRP3 inflammasome were expressed in extracellular vesicles derived from decidua and decidual stromal cells, indicating the miR-138-5p, GPR124 and NLRP3 inflammasome have potential modulatory role on decidual programming and placentation of human pregnancy. Our findings represent a new concept regarding the role of extracellular vesicles, miR-138-5p, GPR124, and NLRP3 inflammasome in normal early pregnancy and spontaneous miscarriage.