Delta-Like 4-Notch signaling regulates trophoblast migration and invasion by targeting EphrinB2

The migration and invasion of trophoblasts during early pregnancy in known to play an important role in placental development, which ensures the oxygen and nutrients to the fetus. Accumulating evidences suggest that Delta-Like 4(DLL4)-Notch signaling may be involved in the process of trophoblast regulation. However, the potential role of DLL4-Notch signaling as well as its molecular mechanism in trophoblast controlling has not been fully studied. This study is designed to investigate the effects of DLL4-Notch signaling on trophoblast functions in human extravillous trophoblast cell line, HTR-8/SVneo. The possible molecular mechanism of DLL4-Notch signaling in trophoblast was also explored. We observed that activation of DLL4-Notch signaling enhanced cell migration and invasion ability while blockage of DLL4-Notch signaling impaired. Control of DLL4-Notch signaling did not affect cell viability. The expression of EphrinB2 was regulated by DLL4-Notch signaling. In addition, up-regulation of EphrinB2 resulted in the similar effects on trophoblast cell functions as DLL4-Notch signaling activation. Moreover, activation of DLL4-Notch signaling reversed the negative impact of EphrinB2 knock-down on trophoblasts migration and invasion. Our study suggested that DLL4-Notch signaling involved in the regulation of trophoblast migration and invasion, which may be induced by direct regulation of EphrinB2 expression.