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.
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