Role Of Rictor/mTORC2 In Mouse Embryo Implantation

ObjectivePregnancy is a complex process that comprises discrete events including implantation,decidualization,placentation through the process of parturition.Human infertility and abortion have always been global social and economic issues that have attracted widespread attention.Despite the current rapid development of assisted reproductive technology,infertility provided an opportunity for pregnancy.However,it has been found from the research of assisted reproductive technology that the success rate of embryo implantation remains at a low level.Effective reciprocal cross-talk between the receptive uterus and a competent blastocyst is critical for successful implantation.To date,several transcription factors,autocrine/paracrine factors and post-transcriptional factors have been confirmed to collectively regulate the process.mTOR signaling pathway as a regulatory center for cell proliferation,growth and survival.mTORC2,one of the main members of mTOR,for embryo implantation has not been reported.In order to lay the foundation for exploring the role and related mechanisms of Rictor in mouse embryo implantation.The expression profile of rictor/mTORC2 in the endometrium of early pregnant mice were explored.Methods1)The mouse model of early pregnancy were established.2)The mouse model of Rictor gene uterine-specific knockout were established.ResultsImmunohistochemistry results showed that Rictor mainly expressed in the luminal and glandular epithelium in the D1 of pregnancy（D1 for short）to D4 and sustained highly expressed in decidual zone surrounded implantation site after embryo implantation.The conditional knockout mice withgenotypeRictor^fl/flCre^+/-weresuccessfullypropagated.Immunohistochemistry,Western blot and RT-qPCR showed that the expression of Rictor was decreased significantly in mouse uterus which indicated that Rictor uterine conditional knockout mice were successfully established.Compared with the control mice,the size and weight of the uterus of the knockout mice were significantly lower（P<0.01）.The uterus of D5 in conditional knockout mice showed no visible embryo implantation sites and the expression of Ki67 and MUC1（markers of proliferation and endometrial receptivity）in the luminal epithelial cells increased significantly.Conclusion1.Rictor may regulate endometrial receptivity or stromal cell decidualization and participate in mouse endometrial embryo implantation;2.The embryo implantation is blocked and the implantation rate is significantly reduced in conditional knock out mouse;3.Normal uterine receptivity was impaired after conditional knockout Rictor.