| BackgroundEmbryo implantation refers to the process of implantation of blastocysts with receptive endometrium.The success of embryo implantation depends not only on whether the embryo can develop into blastocysts with implantable ability,but also on the endometrial synergistic entry into the receptive state of the embryo.With the continuous development of assisted reproductive technology(ART),the quality of embryos has been greatly improved,but the implantation rate of clinical embryo transfer is less than 50%,still hovering at a low level,and even multiple transplant failures.At present,most scholars believe that recurrent implantation failure(RIF)is 40 years of age infertility women who have received fresh or frozen thaw cycles transplant ≥ 3 times and transplanted high quality embryos ≥ 4 still can not normal pregnancy,resulting in RIF factors include gamete / embryo factors,uterine factors,immune factors,thrombosis and so on.The exact mechanism at which RIF are present is still unclear,and it is known that 2/3 of RIF is caused by endometrial receptivity disorders.Endometrial receptivity refers to the endometrial tissue in sex hormones,cytokines,adhesion molecules and glycoproteins and other factors under the control of a series of changes to have the ability to tolerate embryo implantation,it is crital for the embryo of normal implantation.Kisspeptin is a polypeptide hormone encoded by the KiSS-1 gene,which binds to its specific receptor GPR54 to inhibit tumor metastasis and can regulate the release of gonadotropin in the hypothalamic pituitary level,thereby regulating reproductive function and participating in puberty initiation,Regulation of follicular development and ovulation and other biological processes.Kisspeptin/GPR54 system in the endometrial expression,can regulate the embryonic trophoblast in the endometrial migration and invasion,participate in endometrial decidualization,embryo implantation,placental formation and other biological processes,in the establishment and maintenance of pregnancy play an important role.Secretory glycoprotein LIF belongs to the family of interleukin-6(IL-6),which is differentially expressed in different menstrual cycles in the endometrium.Its expression is in the corpus luteum and reached its peak in the late stage.External evaluation of endometrial receptivity of one of the main related markers in the endometrial receptivity of the establishment and endometrial decidualization process plays an extremely important role.In recent years,it has been found that Kisspeptin/GPR54 system is expressed in the maternal-fetal interface at the early stage of gestation,and its expression level is affected by E2 and P4.KiSS-1-/-gene knockout mice have the expression of LIF in the endometrium Low,in addition to exogenous LIF,can partially remediate mutant female(KiSS-1-/-)embryo implantation.It is speculated that the Kisspeptin/GPR54 signaling pathway may be involved in the process of mouse embryo implantation by regulating the expression of LIF on the endometrium.The above data are derived from animal experiments.Then,how the expression of Kisspeptin,GPR54,and LIF in the endometrium of human RIF implantation window was changed compared with the normal control group.Whether this change was related to the endometrial tolerance of RIF patients.Related experiments on the above issues for a preliminary discussion.Purpose:To investigate the expression and localization of Kisspeptin,GPR54 and LIF in the endometrium of normal pregnant women and patients with RIF,and to explore the factors that affected the endometrial tolerance of patients with RIF.To improve the endometrial receptivity of RIF patients and improve the ART medium embryo implantation rate and pregnancy rate to provide a theoretical basis.Methods:The patients who received IVF-ET/ICSI-ET/Thaw-ET in the Reproductive Medicine Center of the First Affiliated Hospital of Zhengzhou University from October 2010 to March 2017 were selected for hysteroscopy in the mid-luteal phase or endometrial irritation to collect their endometrium,through the routine pathological examination to determine its secretory phase,through real-time quantitative PCR and immunohistochemical techniques to detect Kisspeptin,GPR54 and LIF in normal pregnant women and repeated transplant failure patients The expression and location of the endometrium were measured and analyzed statistically.Results:1.Real-time fluorescence quantitative PCR results showed that the mRNA of Kisspeptin,GPR54 and LIF were significantly decreased in the endometrium of RIF group compared with normal pregnancy group;2.The results of immunohistochemistry showed that LIF was mainly expressed in the cytoplasm and cell membrane of endometrial glandular epithelium and luminal epithelial cells,and a small expression was observed in stromal cells.Kisspeptin and GPR54 were mainly expressed in the uterus of the cytoplasm and cell membrane of glandular epithelial cells,Kisspeptin in the stromal cells almost no expression,GPR54 in stromal cells have a small amount of expression;by the integral optical density analysis,compared with the normal pregnancy group,in the endometrium of RIF group women,the expression was significantly lower.Conclusion:1.The expression of Kisspeptin,GPR54 and LIF decreased in the endometrium of patients with repeated graft failure;2.The expression characteristics and changes of Kisspeptin and GPR54 in the endometrium of normal women and RIF patients were consistent with that of LIF.Kisspeptin and GPR54 may also be involved in the changes of endometrial receptivity in patients with RIF. |
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