Osteopontin regulates trophoblast proliferation and invasion and associates with spontaneous abortion during early pregnancy

Trophoblast proliferation and invasion are the hall marks of early placental development, defects in trophoblast proliferation and invasion may lead to early pregnancy loss. However, the key molecules that participate in these processes are largely unknown. The study presents here showed that the mRNA and protein levels of osteopontin (OPN) are down-regulated in placental villi tissue from patients with spontaneous abortion when compared with the matched induced abortion group. Knockdown of OPN expression in human choriocarcinoma trophoblast cell line of JEG-3 with OPN shRNA plasmid could attenuate trophoblast proliferation and invasion. PI-3k inhibitor treatment will block the OPN induced P-AKT and MMP-9 expression in JEG-3 cells. In summary, this work describes a direct, positive effect of OPN on the control of human trophoblast invasion by modulation of MMP-9 expression through PI-3k/AKT signal pathway, suggesting that OPN is involved in the pathological process of spontaneous abortion that characterized by insufficient trophoblast invasion.