Here, reduced syncytin-1 was identified in the late-onset preeclampsia placentas. Reduced syncytin-1 may attenuates the EMT process by promoting apoptosis, inhibiting proliferation and invasion by suppressed PI3K/Akt pathway in trophoblast cells. Our findings provide novel insights into the non-fusogenic biological function of reduced syncytin-1 that may be involves in the pathogenesis of preeclampsia.