Introduction: Low molecular weight heparin (LMWH) is widely administered to women with previous pregnancy complications. Several studies have shown a favorable effect of LMWH on pregnancy outcome but the mechanism is still unclear .
Objective: We hypothesized that LMWH might minimize hypoxic injury of trophoblasts and, hence improve pregnancy outcome .
Methods: Jeg-3 cells were cultured for 24 hours in either standard conditions (O2=20%, (cobalt chloride (0.2 mM), a hypoxia mimetic agent, or hypoxia (O2< 1%) with and without exposure to increasing concentrations (1, 10 and 100 ng/ml) of Enoxaparin. Enoxaparin (Sanofi-Aventis, France) In order to investigate the effect of Enoxaprine on trophoblasts we measured the secretion of HCG to culture medium .
Results: HCG secretion was reduced significantly when throphoblasts were exposed to CoCl2 or hypoxia. Enoxaparin does not influence HCG secretion in standard conditions. Interestingly, Enoxaparin significantly protected JEG3 cells from hypoxic injury as expressed by increased HCG secretion .
* A Comparison of HCG secretion at hypoxia and CoCl2 to control, P<0.05
** A Comparison of HCG secretion in cells exposed to Enoxaparin 10 and 100 ng/dl to Enoxaparin 1 ng/ml, p<0.05
Conclusions: Enoxaparin protect trophoblasts from hypoxic injury as demonstrated by its effect on HCG secretion. Further studies are required to define this novel effect and determine the mechanism behind this effect including HIF1 involvement. If this effect is established it might reveal a mechanism by which Enoxaparin prevents placental hypoxic injury and finally prevents pregnancy complications .
Authors:
Eli Rimon, Joseph B Lessing, Michael J Kupferminc
Tel Aviv Medicl Center, Tel Aviv University, Tel Aviv, Israel