Function Regulation of EPO at Human Maternal-Fetal Interface in the Early Pregnancy
|Course||Obstetrics and Gynecology|
|Keywords||Erythropoietin Hypoxia-inducible factor Abortion|
Objective To observe the erythropoietin EPO (erythropoietin, EPO) and its receptor (Erythropoietin Receptor EPOR) during early pregnancy in the mother - fetal interface function adjustment, and its abnormal expression in the incidence of spontaneous abortion and possibly signaling pathway. Methods trimester spontaneous abortion villi and decidua 20 cases, each using immunohistochemistry, RT-PCR, Western blot detection of EPO, EPOR and HIF-1alpha expression, and Western blot analysis of downstream signaling molecules STAT5 p38, JNK, ERK, AKT activation. And through in vitro studies, outside the velvet nourish the role of endometrial stromal cells, the cell lines HTR-8/SVneo and primary cultured medium with different concentrations of anti-EPO antibodies and the EPO detection of trophoblast invasion capacity and nourish cells and endometrial stromal cells, cell viability, proliferation and apoptosis. EPO and EPOR in early pregnancy mother - fetal interface trophoblast cells, endometrial stromal cells and epithelial cells have a strong expression; whether in mRNA or protein levels, spontaneous abortion compared with normal pregnancy group expression was significantly lower (p lt; 0.05). Further analysis of Stat5, p38, JNK, ERK, Akt activation found villi and decidua of spontaneous abortion anti-apoptotic factor activation of STAT5 was significantly lower than normal chorionic tissue (p lt; 0.01); but JNK, ERK, Akt in two no significant difference (p gt; 0.05) in the group. The spontaneous abortion organization of pro-apoptotic factor p38 activation was significantly higher than normal early pregnancy tissue (p lt; 0.01). Normal chorionic villi and decidua of HIF-1alpha expression; spontaneous abortion organizations expressed lower (p lt; 0.05) Anti-EPO antibodies to a dose-dependent inhibition of to nourish cell invasion, inhibition of cell viability and proliferation of trophoblast cells and endometrial stromal cells, can be a time-and dose-dependent manner, and significantly contribute to both cell apoptosis. Conclusion EPO and EPOR In the normal early pregnancy - maternal interface high expression may be involved in the maintenance of normal pregnancy; decreased expression resulted in the occurrence of spontaneous abortion. In normal pregnancy - maternal interface, EPO downstream anti-apoptotic factor STAT5 activation and inhibition of the activation of pro-apoptotic factor p38; EPO on STAT5 and p38 abnormal regulation of trophoblast cells and endometrial stromal cells, apoptosis, leading to the final resulting in pregnancy failure. HIF-1alpha as EPO upstream regulatory factors, in normal pregnancy villi and decidua higher expression; HIF-1alpha expression decreased, which may affect the regulation of the EPO - maternal interface, resulting in pregnancy failure. Our in vitro studies further confirmed that the mother during early pregnancy - fetal interface EPO regulation of trophoblast cells and endometrial stromal cells, the biological behavior, participation in early pregnancy the placenta is formed.