Plasma F2-isoprostane class VI isomers at 12–18 weeks of pregnancy are associated with later occurrence of preeclampsia

Abstract

Preeclampsia (PE) has long been associated with early oxidative stress, although the symptoms occur later in pregnancy. We have hypothesized that the oxidative stress in PE, as characterized by the presence of F2-isoprostane (F2-isoP) isomers in late pregnancy, should already be present in plasma at the first regular visit of the obstetrical follow-up. There are 64 possible isomers of F2-isoPs derived from the oxidation of arachidonic acid (AA), but only one of these isomers has been investigated so far in PE, the classical 8-iso-PGF2α. Here, we have investigated two regioisomers of class III (8-iso-15(R)-PGF2α and 8-iso-PGF2α) and a mix of two isomers of class VI ((±)5-iPF2α-VI) in plasma samples collected prospectively at 12–18 weeks from normotensive controls (n = 60) and pregnant mothers who developed PE later in pregnancy (n = 33). The plasma samples were subjected to alkaline hydrolysis followed by liquid–liquid extraction to extract total F2-isoPs for later quantification by HPLC-MS/MS. The F2-isoPs were normalized to either plasma volume or polyunsaturated fatty acid (PUFA) levels measured by GC-FID in plasma phospholipids. Early in pregnancy, only the class VI F2-isoP isomers were found at concentrations significantly higher in women developing PE later in pregnancy (+13%; p = 0.0074). Normalization of F2-isoPs to their substrate, AA, or the omega-3 to omega-6 ratio improved the predictability of PE as determined by receiver operating characteristic (from area under the curve of 0.67 to 0.68 and 0.70 respectively). Interestingly, omega-3 fatty acids were 25% higher in the control group than in the PE group (P = 0.0225). Omega-6 PUFAs correlated with F2-Isop isomers only in cases of PE (r > 0.377; P >0.03, Spearman correlation). In sum, this study indicates that specific isomers of class VI are significant predictors of PE. This work also suggests that F2-isoP isomers are not all generated and eliminated to the same extent and are influenced by the PUFA composition of plasma phospholipids.