Molecular Biology And Immunology Mechanism Of Integrin αvβ3in The Embryonic Development

Embryo implantation is the result of embryos and maternal bidirectional regulation that involved immune cells, immune molecules, cytokines, adhesion molecules, etc, is an extremely complex physiological process.The two functions of the integrin mediated adhesion and signal transduction play an important role in the embryo implantation,mmune, wound healing and so on the Physiological and pathological process. in recent years, adhesion molecules, especially the role of integrin in embryo implantation is becoming more and more attention, has become one of research hot spots. The study found that avβ3integrin is identified molecules of the receptivity of endometrium when reaches the supreme state begin to express in the receptivity of endometrium. A variety of integrin in the embryo, endometrium and placenta expression play an important regulating role in the process of embryo implantation, avβ3integrin directly involved in the identification adhesion of endometrium and trophoblast cell adhesion and trophoblast cell infiltration, regulating of embryo.This article used the siRNA interfering technology, designed a siRNA interference frag ment of Human Villous Trophoblasts integrin alpha V, fitered the high efficient of the sil ent especial serial of siRNA of integrinaV.Packaged retro virus with high efficiency siR NA silence builded a retrovirus carrier which induced siRNA silencingaV gene of the stable HVT cell line, successfully. Immunofluorescence and co-immunoprecipitation technology found a interaction site of SPP1protein with integrinaV. The research found that after the integrinaV gene silenced, the stimulation of SPP1to the phosphorylation of mTOR,AK,p38,ERK, P70S6K and RPS6protein was weakened, but there has no eff ect to PDK1protein; and also weakened the proliferation of HVT cells.By tail vein injection of integrin avβ3antagonists SB-273005was found that the experimental mice embryos and pregnancy rate dropped significantly (P<0.05). HE staining showed SB-273005can lead to endometrial decidual incomplete, such as thickening of decidual, interstitial edema with a large number of inflammatory cells infiltration or decidual thin, dense stroma, hyperchromatic cells, immunohistochemical, RT-PCR、Western Blot all result has showed that SB-273005could make mice embryos implanted window and the expression quantity of avβ3in the endometrium decreased significantly. besides, on the basis of the unaltered expression of the total FAK. AKT、ERK1/2,the expression of p-FAK、p-AKT、p-ERKl/2on the endometrium are reduced obviously, SB-273005may inhibited the transduction process of the signal which is mediated by integrinavβ3, and eventully inhibited the survival, proliferation and migration of trophoblast, and impacted that the embryo implanted to endometrial; SB-273005can also causeed the low expression of CyclinDl, the high expression of P21cipl, leaded the complete cell cycle cannot finished in order, induced the apoptosis, thus influenced the embryo implanting to endometrial.Treated NK cells with SB-273005and the Thl/Th2ratio increased dramaticlly in the mouse Peripheral Blood,the level of IFN-γ was markedly increased,illustrated that SB-273005can increase the level of pNK cells, improve the odds of miss gestation; The experimental group mouse serum have higher concentration of IL-2、TNF、IFN-γ、 IL-17A,and lower concentration of IL-6, IL-10, SB-273005added the count of NK cells and Thl cells in peripheral blood, and increased the immunotoxicity of murine and rejected that embryo enter intouterus.Above research, we can conclusive that,integrin involved in the PI3K-AKT1and FRAP1-P70S6K-RPS6signal transduction pathway, it could be a supplement to the cell signaling pathways. We will deeply explore that blocking avβ3may influenced embryo implantation:for one thing is impeded recognition between cells, adhesion and migration, disturbed immediately trophoblast cells identification and adhesion with intrauterine, suppressed embryo invasion and development; for another thing, reversed the advantages of Th12cells and cytokines during gestation,cutted off the tolerant formation, suppressed embryo implantation, this article illuminated that intergrinavβ3regulate and control the mechanism of embryo implantation preliminary, and provides theoretical foundation for the new type contraception development.