Endometrial cell-derived small extracellular vesicle miR-100-5p promotes functions of trophoblast during embryo implantation

Communication between maternal uterus and blastocyst occurs in the early stages of pregnancy, and the interaction influences the success of embryo implantation. Whereas small extracellular vesicles (sEVs) play an essential role in mediating intercellular communication in numerous biological processes, their role in embryo implantation during the window of implantation (WOI) remains poorly defined. Here, we report that endometrial epithelial cells (EECs) secrete sEVs during early pregnancy, which affects the trophoblast behaviors (migration, invasion, and proliferation), thus influencing embryo implantation. We show that microRNA (miR)-100-5p, sEVs containing microRNA (miRNA), activates both focal adhesion kinase (FAK) and c-Jun N-terminal kinase (JNK), as well as contributes to trophoblast migration and invasion. Furthermore, our findings indicate that the sEV miR-100-5p promotes angiogenesis during the implantation process. In conclusion, this study reveals a novel mechanism by which EEC-derived sEV miR-100-5p crosstalks with trophoblasts, leading to an enhanced ability for implantation.