Endometrial Extracellular Matrix Rigidity and IFNτ to Ensure the Establishment of Early Pregnancy Through Activation of YAP

In mammalian, early pregnancy is a critical vulnerability period during which complications arise and pregnancy failure. The establishment of maternal endometrial acceptance phenotype is a prerequisite for semi-heterogeneous embryo implantation, and it is also the rate-limiting step of early pregnancy. Here we indicated that the YAP (Yes-associated protein) translocate into the nuclei in the endometrium of cattle and mouse in early pregnancy. Mechanically, YAP acts as nuclear relays of ECM rigidity and cell density, that act requires the actomyosin cytoskeleton and partially dependent Hippo pathway. Furthermore, we found that the soluble factor IFNτ, which is a ruminant pregnancy recognition factor, can also induce the activation of YAP by reducing the expression of miR-16a. This promoted expression of certain endometrial receptor genes, induced cell proliferation and establishes a local immunosuppressive environment that allows conceptus implant to the uterine epithelium. It is consistent with the results of the mouse pregnancy model and pseudo-pregnancy model. These findings provided a novel insight into how the endometrium responds to signals from the cellular microenvironment in early pregnancy. Funding Statement: This study was supported by the National Natural Science Foundation of China (31772816). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: All mouse experiments were conducted in accordance with the university guidelines on animal experimentation (HZAUMO-2015-12), and approval by the Animal Ethics Committee of the Huazhong Agricultural University was obtained for all related procedures.