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 expre...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.展开更多
基金This work was supported by grants from the Ministry of Science and Technology of China(2011CB966302,2013CB947900,2014CB910601,and 2013CB945502)the National Natural Science Foundation of China(81430065 and 31371388)+1 种基金the Fundamental Research Funds For Central Universities(WK2070000034)a Special Research Fund for the Doctoral Program of Higher Education from Ministry of Education of China(20123402130006).
文摘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.
