The Effect Of Low Molecular Weight Heparin On Trophoblasts

Background: It was suggested that administration of low molecular heparin (LMWH), an anticoagulant agent, prevents recurrent pregnancy complications among women with thrombophilia. Importantly, recent studies have suggested that the favorable effect of LMWH is not dependent upon its anticoagulant effect. The aim of the study was to investigate the influence of LMWH on trophoblasts.

Methods: Jeg-3 cells were cultured for 24 hours in either standard conditions (O2=20%), hypoxia (O2< 1%) or in hypoxia mimetic agents with and without LMWH (Enoxaparin). In order to investigate the effect of Enoxaparin on trophoblasts differentiation we measured the secretion of human chorionic gonadotropin (hCG) to culture medium and expression of Syncytin. In addition, we investigated the effect of Enoxaparin on cleavage of poly (ADP-ribose) polymerase (PARP), M-30 expression, caspase 3 cleavage and p53 expression as markers of trophoblasts apoptosis.

Results: hCG secretion and expression of Syncytin were reduced significantly when trophoblasts were exposed to hypoxia. Interestingly, Enoxaparin significantly protected JEG3 cells from hypoxic injury as expressed by increased hCG secretion and syncytin expression. Enoxaparin had an anti apoptotic effect on trophoblasts as determined by: cleavage of PARP, M-30 expression, caspase 3 cleavage and P53 expression.

Conclusions: Enoxaparin has a favorable effect on trophoblasts differentiation and prevention of apoptosis. The data suggest a possible mechanism by which Enoxaparin prevents placental hypoxic injury and finally prevents pregnancy complications.

Authors:

Eli Rimon, MD

Lis Maternal Hospital, Tel Aviv Medical Center