Effects Of Insulin-like Growth Factor-I And Study Of Mitogen-Activated Protein Kinase On Human Trophoblast Cells Of Early Pregnancy

Objective: Our aim was to study the expression of mitogen-activated protein kinase in human chorionic villi of early pregnancy, to investigate the roles of insulin-like growth factor-1 and the effects of MAPK singal pathway on human trophoblast cells cultured in vitro of early pregnancy, and to explore the part of molecular mechanism of trophoblast cell during the process of implantation.Methods: The expression of MAPK in human chorionic villi of early pregnancy was measured by immunohistochemistry technology , Western Blotting and image analysis. The roles of insulin-like growth factor-I and the effects of MAPK singal pathway on human trophoblast cells cultured in vitro of early pregnancy were investigated by cell ELISA, MTT assay, and so on. U0126, the specific inhibitor of ERK/MAPK signal pathway was used to reflect indirectly the possible involvment of ERK pathway on trophoblast cells.Results: In the present study, we found: (1) Phosphate-ERK was expressed in both cytotrophoblast and syntrophoblast in human chorionic villi of early pregnancy, but the expression area and expression intensity of them in natural abortion group were significantly lower than normal group. Phosphate-p38 and phosphate-JNK were expressed in both cytotrophoblast and syntrophoblast in human chorionic villi of early pregnancy in normal group, but they were only expressed in cytotrophoblast in natural abortion group. (2) The expression level of p-ERK in normal group was significantly higher than that of natural abortion group by Western Blotting analysis. (3) Different concentration of insulin-like growth factor-1 could activate ERK on human trophoblast cells cultured in vitro of early pregnancy by cell ELISA assay. Moreover, The activation of ERK showed a concentration-dependent manner. (4) There were siginificant difference in activity of proliferation and HCG secretion between experimental groups of IGF-1 above 10nM and the control one on human trophoblast cells cultured in vitro of early pregnancy by MTT and ECL assay. The activity of proliferation and HCG secretion showed a dose-dependent manner in the same way. (5) U0126, the specific inhibitor of ERK signal pathway could restrain significantly the effects of IGF-1 on trophoblast cells including ERK activation, cell proliferation and HCG secretion. (6) IGF-1 could not stimulate the activity of migration but U0126 could inhibit it on human trophoblast cells cultured in vitro of early pregnancy.Conclusion:1) MAPK pathway maybe is one of important signaling pathways in the process of proliferation, differentiation and invasion of trophoblast cells in human early pregnancy.2) Insulin-like growth factor-I has promoting effect on the proliferation and differentiation of trophoblast cell.3) ERK/MAPK signaling pathway maybe play an important role on the effects of proliferation and differentiation of IGF-I on human trophoblast cell in vitro of early pregnancy.