Preeclampsia is a pregnancy-specific syndrome that is the leading cause of maternal death during pregnancy in the developed world. In preeclampsia, a combination of immunological, genetic and environmental factors can lead to altered cytotrophoblast (CTB) invasion of the uterine wall, a process that is critical for normal placental development and pregnancy maintenance. Marinobufagenin (MBG) is an endogenous inhibitor of the sodium pump Na(+)/K(+) ATPase, and increased plasma MBG is associated with hypertension, chronic renal failure and preeclampsia. In the present study, the effects of MBG on CTB differentiation and invasion were investigated utilizing the first trimester extravillous CTB cell line SGHPL-4. MBG significantly inhibited SGHPL-4 proliferation in a dose-dependent manner. In addition, growth factor-induced migration and invasion were significantly inhibited by MBG treatment. These findings demonstrate that MBG impairs CTB differentiation along the invasive pathway. Elucidating the mechanisms by which MBG impairs placental development may increase our understanding of fetal and maternal pathologies associated with preeclampsia.