Specific systemic antioxidant response to preeclampsia in late pregnancy: the study of intracellular glutathione peroxidases in maternal and fetal blood

Abstract

The physiopathology of preeclampsia is still unclear, but an imbalance between reactive oxygen species (ROS) and antioxidants, also called oxidative stress, appears to be an important contributing factor. The ROS promote lipid oxidation and are known to induce stress proteins, such as hemeoxygenase 1 (HO-1) and heat-shock protein 70 (Hsp-70). We hypothesized that glutathione peroxidases (GPx), a major class of antioxidant enzymes that regulate cell homeostasis by neutralizing lipid peroxides, are altered in the blood of preeclamptic women and neonates (venous cord blood). Thirty-one preeclamptic and 30 normotensive pregnancies were recruited. The blood was fractionated using a discontinuous gradient to separate the different cell types. The messenger ribonucleic acid (mRNA) expression of GPx-1 and -4, HO-1, and Hsp-70 were analyzed by quantitative reverse transcriptase-polymerase chain reaction. GPx-1 and -4 protein level in blood cells was also detected by Western blot. The experiments were analyzed using the Student t test. The HO-1 and Hsp-70 mRNA expression in whole blood was significantly higher in both fetal and maternal circulations (P < .05). We also discovered that GPx-4 mRNA was 1.6-fold higher in blood of women with preeclampsia than in control pregnancies (P = .04). The latter was associated with an increase of both GPx-1 and GPx-4 protein and mRNA levels in the lymphocyte/monocyte fraction of the blood. Significantly higher GPx-4 mRNA levels in the fetal circulation of the preeclamptic group than the control group were also detected (P < .001). These data indicate that preeclampsia is associated with a specific antioxidant response in both maternal and fetal circulations, likely in response to the deleterious oxidative stress observed in this syndrome.