Heparin and aspirin attenuate placental apoptosis in vitro: implications for early pregnancy failure.

Live birth rates are increased by treatment with heparin and aspirin in cases of poor pregnancy outcome such as antiphospholipid syndrome. Both drugs may attenuate miscarriage by inhibiting aberrant coagulation or by modulating trophoblast apoptosis. Here we assessed their roles in trophoblast apoptosis in vitro. BeWo cells and placental villi were cultured in sera from women with successful or failing in vitro fertilization, with and without heparin or aspirin. Apoptosis was assessed by using DNA laddering, cytokeratin 18 neoepitope formation, Bcl-2, and caspase 7 expression. In BeWo cells, sera from in vitro fertilization failure increased trophoblast apoptosis, whereas heparin and aspirin reversed these effects. In villous trophoblast, heparin increased Bcl-2 and cytokeratin 18 protein expression. Heparin and aspirin inhibited DNA laddering. Heparin and aspirin modulate trophoblast apoptosis suggesting a direct impact on trophoblast biology, thus providing an additional mechanism to explain the clinical benefits of heparin and aspirin on recurrent pregnancy loss.