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 regu-lated by the transcriptional factor Emx2,and the Emx2–miR-181 axis plays an importantrole 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.