Maternal serum of women with pre-eclampsia reduces trophoblast cell viability: Evidence for an increased sensitivity to Fas-mediated apoptosis

Objective: Pre-eclampsia or 'toxemia of pregnancy' has been attributed to the presence of a circulating 'toxin' which disappears from peripheral blood after delivery of the placenta. However, the presence, nature and effects of this toxin have eluded characterization. Increased trophoblast apoptosis has been observed in the placenta of women with pre-eclampsia, and it is possible that this biological phenomenon is important for the genesis of the disease and mediated through a soluble factor(s) present in maternal blood. This study was designed to test the hypothesis that serum from women with pre-eclampsia changes trophoblast viability. Moreover, we sought to examine whether this effect could be mediated through changes in sensitivity to Fas/Fas ligand-mediated apoptosis. Study design: H8 trophoblast cells were cultured with serum obtained from normal pregnant women (n = 48) and patients with pre-eclampsia (n = 12). Cell viability was determined by the Cell Titer 96 assay. Fas sensitivity was determined by treating the cells with an agonist anti-Fas antibody or a blocking anti-Fas ligand antibody. Results: Serum from normal pregnant women did not affect trophoblast cell viability. In contrast, serum from pre-eclamptic women reduced trophoblast viability, and this was enhanced by treatment with an anti-Fas antibody. This effect was reversed by the treatment with a blocking anti-Fas ligand antibody. Conclusion: Serum from women with pre-eclampsia induces the cytotoxicity of a first-trimester trophoblast cell line (H8). This effect appears to be related to changes in trophoblast sensitivity to Fas-mediated apoptosis. These findings suggest that a factor present in the maternal blood of patients with pre-eclampsia may have a role in the genesis of the syndrome.