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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Bose
Patrick
P
Department of Anatomy II, University Hospital RWTH, Aachen, Germany.
Black
Simon
S
Kadyrov
Mamed
M
Weissenborn
Ute
U
Neulen
Joseph
J
Regan
Lesley
L
Huppertz
Berthold
B
D000026:Abortion, Habitual / Q000473:pathology / Q000517:prevention & control; D000925:Anticoagulants / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002460:Cell Line / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005307:Fertilization in Vitro; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D010920:Placenta / Q000187:drug effects*; D010922:Placenta Diseases / Q000473:pathology / Q000517:prevention & control*; D011247:Pregnancy; D011250:Pregnancy Complications, Hematologic / Q000473:pathology / Q000517:prevention & control*; D014327:Trophoblasts / Q000187:drug effects
D000925:Anticoagulants; D006493:Heparin; D001241:Aspirin