Function Regulation Of Epo At Human Maternal-fetal Interface In The Early Pregnancy

Objective In order to investigate EPO and EPOR expression at maternal-fetal interface to find their possible function and signal pathway in human early pregnancy.Methods Villi and decidua were obtained from normal human pregnancy (n=20) and miscarriage (n=20) during the first trimester of pregnancy. EPO, EPOR and HIF-1αexpression was investigated by RT-PCR, Immunohistochemistry, and Western Blot. The phosphorylation of STAT5, p38, JNK, ERK, AKT was detected by Western Blot. The invasiveness and viability, proliferation and apoptosis of trophoblasts as well as decidual stromal cells with or without neutralizing antibody to EPO were detected in vitro study. Results We demonstrated the strong expression of EPO and EPOR in trophoblasts, decidual stromal cells and glandular epithelium cells in human first trimester pregnancy. In mRNA and protein level, EPO and EPOR expression decreased in the miscarriage as compared to normal pregnancy (p<0.05). The phosphorylation of STAT5 other than AKT, JNK, ERK was obviously down-regulated, and that of p38 was significantly up-regulated in the villus and decidua of miscarriage (p<0.01, p<0.05). HIF-1αexpression was down-regulated in the villus and decidua of miscarriage as compared to normal pregnancy (p<0.05). With neutralizing antibody to EPO, the invasiveness of trophoblasts was greatly down-regulated, as well as the viability, proliferation of trophoblasts and decidual stromal cells, and the apoptosis of them were up-regulated.Conclusions EPO and EPOR are expressed at maternal-fetal interface in human early pregnancy, and their lower expression leads to pregnancy wastage. The phosphorylation of anti-apoptosis gene STAT5 is up-regulated, but not for AKT, JNK, ERK, and the phosphorylation of proapoptosis gene p38 is significantly decreased in normal early pregnancy with comparison to miscarriage. HIF-1α, a major transcriptional regulator for EPO, is down-regulated in miscarriage. The results of the study in vitro confirm further that EPO can regulate the functions of trophoblasts and decidual stromal cells in human first-trimester placentation.