Research On The Influence And Preliminary Molecular Mechanism Of Homeobox Gene HOXA10 On The Development Of Early Placenta

BackgroundThe successful implantation of the embryo and the normal development of the placenta are critical to normal pregnancy.Placental trophoblast cells invade the endometrium,for the development of embryos necessary nutrition,to maintain the conditions to provide hormone environment.Placental development requires a series of complex cellular events,starting with the formation and differentiation of trophoblast cells;The cells have a variety of functions,involving cell proliferation,embryo implantation,trophoblast cell stem differentiation into villous trophoblast cells,which is the first differentiation of human embryos,the first development of one of the cell types,and fetal cells that are only accessible to the maternal-fetal interface that are in direct contact with the parent immune system play an important role in the process of maternal-fetal immune tolerance during embryo implantation.Trophoblast cell proliferation,migration,lack of invasion and excessive are caused by early placental development abnormalities,and further lead to embryos,fetal death,causing abortion and other pregnancy-related diseases.The homologous framework gene has been known to have important regulatory role in embryonic development.GATA-3 is expressed in trophoblast cells.Pregnancy-induced hypertension develops Th1 / Th2 balance,The development and severity of blood pressure disease are closely related.The low expression of HOXA11 in the choriocarcinoma BeWo cell line promotes the differentiation of the trophoblast to the trophoblast and promotes the development of choriocarcinoma.Suggesting that homologous box genes play an important role in trophoblast cell development.HOXA10 in the process of embryonic development if the gene mutation can cause Mau Le tube development abnormalities,causing double uterus,uterine mediastinal and other deformities.And it has not been studied in the early stages of embryonic development,that is,early placental development.In this study,the expression of HOXA10 in early placental tissue was significantly higher than that in middle and late placental tissue by gene chip technique,which showed a significant decrease in early placental development,The necessity and related molecular mechanism of HOXA10 on trophoblast cell proliferation were further discussed.Purpose To investigate whether HOXA10 affects trophoblast cell proliferation by regulating the expression of cyclin-dependent protein kinase inhibitor p57 Methods 1.Mouse placenta development as the model,the mouse placental development of 6.5d,14.5d and 19.5d of the three cases of tissue,the mRNA chip detection.The gene selection condition was Fold change> 2.0,P <0.05,and the homologous box gene HOXA10 related to the early placental development was screened out.2.The results of RT-PCR and western blot were used to test the results of early,middle and late advanced placenta.3.In the trophoblast cell line HTR-8 / SVneo,the expression of cyclin-dependent protein kinase inhibitor p57 was detected by small interfering RNA interference HOXA10 expression,and the related proliferation function test was carried out.4.The expression of HOXA10 in villous tissues,villi tissues and villi tissues of spontaneous abortion was detected by IHC.Results 1.The expression of HXXA10 in human placenta was significantly higher than that in middle and late placenta.2.The cell proliferation ability of human trophoblast cells HTR-8 was significantly decreased after HOXA10 expressionCyclin-dependent protein kinase inhibitor p57 is the highest expression of cyclin in the early trophoblast cells,interfering with the high expression of p57 after HOXA10,and inhibiting the cell cycle.Flow cytometry was used to detect the number of cells in each cycle.(P <0.05).The results of CCK8 test showed that the cell proliferation ability was significantly decreased(P <0.05).3.The expression of HOXA10 in human trophoblast cells did not change significantlyThe expression of HOXA10 did not affect the apoptosis of trophoblast cells by interfering with HOXA10 in trophoblast cells after flow cytometry(P <0.05).4.The expression of HOXA10 in villi was significantly lower than that in complete hydatidiform mole,which was significantly higher than that in spontaneous abortion.Conclusion 1.In placental development,HOXA10 in the process of expression with time and space differences,mainly involved in early placental development.2.By regulating the cyclin-dependent protein kinase inhibitor p57,HOXA10 may increase the trophoblast cell proliferation level,which is to ensure a smooth basis for pregnancy.