| BackgroundRepeated implantation failure(repeated implant failure,RIF)the specific molecular mechanism is not very clear,now known as the 2/3 RIF is caused by uterine receptivity disorders,the reason may be associated with immune,Immunological studies have indicated that pregnancy is a kind of allograft rejection,normal pregnancy embryo,half body tissue antigen by maternal rejection and survival,have a certain relationship with decidual tissue and normal immune microenvironment.Uterine natural killer cell(uterine natural killer cell,uNK)surface specific marker is CD56,most of the uNK cell phenotypes are CD(56bright),CD16(-),low cytotoxicity,secretion of immune regulatory cytokines,vascular growth factors and so on,play an active role in the regulation of the immune regulation of implantation and decidua.Repeated implantation failure patients with secretory rate of CD56+ cells was higher than that of normal women,suggesting that uNK cells may be repeated implantation failure to a certain role in the regulation of endometrial receptivity play.Interleukin-15(interleukelin-15,IL-15)belongs to Th1 related cytokines,studies have shown that it can promote the differentiation and function of NK cells,upregulation of the expression of IL-15 mRNA in normal endometrial secretion,increased secretion of advanced preparation for embryo implantation.Whether the expression of IL-15 increases in secretory phase in repeated failure patients needs to be studied further.Studies have suggested that when TNF-? expression is too high,breaking the implant window Th1 / Th2 factor balance,inhibition of endometrial decidualization process,to promote epithelial cell apoptosis,increase Th1 type cytokine immune response,blocking nourish The invasion of cells produces prostaglandins and activates metalloproteases(MMPs)such as MMP-2 and MMP-9,degrading villous extracellular matrix,triggering early pregnancy failure.Therefore,uNK cells and embryo planting,fetal growth and early placenta is closely related to this relationship once the loss of balance,it will cause repeated planting failure or spontaneous abortion.Changes in the balance of various immune factors may lead to embryo implantation failure,so this study examined the changes in the expression of CD56,IL-15,TNF-? in the endometrium of RIF,and explored its correlation with the occurrence of RIF.Objective1.The expression of IL-15,CD56 and TNF-? were detected by RIF and endometrium in normal secretory phase.2.To explore the expression of IL-15,CD56 and TNF-? in endometrium,and to provide the theoretical basis for the clinical treatment of RIF patients.MethodsThe research topic was approved by the Ethics Committee of the First Affiliated Hospital of Zhengzhou University.All the subjects in the study had informed the contents of the experiment and signed the informed consent form.From September 2016 to March 2017 in our hospital reproductive center IVF-ET/ICSI-ET/Thaw-ET progesterone selection help pregnant pregnancy history to help pregnant again for the control group,at least 4 high-quality embryo transplantation Transplantation or at least three fresh or frozen cycle after cycle,failed to achieve clinical pregnancy patients into experimental group.This study is divided into two parts,the first part of the experiment including 10 cases in the control group and 12 cases in the experimental group,the expression of quantitative qRT-PCR method was used to detect CD56,IL-15,TNF-? in endometrial;The second part of the experiment,including 10 cases of the control group and 12 cases in the experimental group,using immunohistochemical method to detect endometrial CD56,IL-15,TNF-? qualitative and expression of.Results1.The results of qRT-PCR assay showed that CD56,IL-15 and TNF-? were both expressed in the normal endometrium of the secretory phase and in the patients with repeated implantation failure,but the expression in RIF group was significantly higher than that in the control group,the difference was statistically significant(CD56:4.533±2.616 vs.1.302±1.163,P=0.002;IL-15:4.064±2.247 vs.1.614±1.713,P=0.01;TNF-?:6.313±1.912 vs.1.479±0.986,P=0.000).2.The results of immunohistochemistry showed that IL-15,CD56,TNF-? in the secretory phase of normal endometrium and repeated implantation failure were expressed in patients with endometrial epithelial and stromal cells,the average optical density of RIF group was significantly higher than the control group,the difference was statistically significant(P < 0.05).3.Elevated expression of CD56 had a high diagnostic efficacy for RIF,and was positively related to the expression of IL-15 and TNF-?(P < 0.05).Conclusion1.The expressions of IL-15,CD56 and TNF-? were increased in the endometrium of repeated implantation failure than in normal endometrium.2.Elevated expression of CD56 is valuable in the diagnosis of RIF,and may be related to the expression of IL-15 and TNF-?.Further studies are needed to confirm this. |
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