Expression Of ATF4Gene In Mouse Endometrium During Peri-implantation Process Of Embryos And In Chorionic Villus Tissue In Early Spontaneous Abortion Women

ObjectiveThe activating transcription factor4(ATF4), recent studies haveshown that it is up-regulated under hypoxia in human cancer tissues. Uponhypoxia stress, ATF4can inhibit cell apoptosis and promote cellproliferation, ultimately make the cell is adaptive responses to tumorhypoxic microenvironment. It is play an important role in incidence anddevelopment of wide variety of malignant tumors. Furthermore, ATF4couldinduce VEGF transcription at the same transcription signaling pathway.Striking similarities were found in behavioral patterns between embryonicimplantation、invasive trophoblastic cells and cancer cells, and so far ithave not been reported about ATF4’s role in reproduction. So the aim of thepresent study was to investigate the role of ATF4in reproduction bydetecting its expression in mouse endometrium during peri-implantationprocess of embryos and in chorionic villus tissue in early spontaneousabortion women.MethodsEndometrium samples were collected from Day0to Day7in early pregnant mice, and the express level of ATF4mRNA on it was determinedby RT-PCR and the expression level of ATF4protein as determined byimmunohistochemistry and Western blotting. Polyclonal antibody of ATF4was injected into the uterus of the early pregnant mice to observe thechanges of the embryos. The expressions of ATF4and VEGF protein andmRNA in villi from first trimester spontaneous abortion were detected byimmunohistochemistry and Fluorescent quantitative polymerase chainreaction (FQ-PCR).Results1. RT-PCR was demonstrated that the expression of ATF4on theendometrium of pregnant mice was stronger than that of nonpregnantmice(P<0.05), and the tendency was gradually augmented as days went.Itreached the highest level at pregnant d4and declined gradually thereafter.The clearest expression of ATF4protein was primarily limited to thesubluminal stromal cytoplasm in the endometrium of mouse. Expressionalmode of ATF4protein was similar with that of the mRNA.2. ATF4antibody resulted in a significant decrease of embryo implantationas compared with the control group.3. Both protein and mRNA expressions of ATF4and VEGF in thespontaneous abortion group were significantly lower than in Control Groupgroup. Their proteins are mainly expressed in syncytiotrophoblast,cytotrophoblast and villous stromal cells. Correlation analysis showed thatthe expression of ATF4was positively correlated with that of VEGF in SAgroup.Conclusion1. ATF4gene may be involved in the decidualization, and promote the embryo implantation.2. Lower expressions of ATF4and VEGF genes in chorionic villus tissuemay participate in the pathogenesis of spontaneous abortion.