miRNA-181 regulates embryo implantation in mice through targeting leukemia inhibitory factor

Embryo implantation is a crucial step in mammalian reproduction. However, little is known regarding the physiological roles of microRNAs in the regulation of embryo implantation. Here we show that a minimum uterine expression of miR-181 is essential for the onset of embryo implantation. Both transient and prolonged transgenic expression of miR-181 led to impaired implantation, which can be rescued by exogenous administration of leukemia inhibitory factor (LIF). Mechanistically, miR-181 is able to directly target LIF and downregulate LIF expression, thereby inhibiting embryo implantation. We also show that miR-181 expression is regulated by the transcriptional factor Emx2, and the Emx2-miR-181 axis plays an important role in regulating embryo implantation. Taken together, these results reveal a novel function of miR-181 in embryo implantation through the regulation of LIF, and also indicate a potential link between miR-181 dysregulation and human embryo implantation defects.