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

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 F-2-isoprostane (F-2-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 F-2-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-PGF(2 alpha). Here, we have investigated two regioisomers of class III (8-iso-15(R)-PGF(2 alpha) and 8-iso-PGF(2 alpha)) and a mix of two isomers of class VI (+/-)5-iPF(2 alpha)-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 F-2-isoPs for later quantification by HPLC-MS/MS. The F-2-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 F-2-isoP isomers were found at concentrations significantly higher in women developing PE later in pregnancy (+ 13%; p = 0.0074). Normalization of F-2-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 068 and 070 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 F-2-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 F-2-isoP isomers are not all generated and eliminated to the same extent and are influenced by the PUFA composition of plasma phospholipids. (C) 2015 Elsevier Inc. All rights reserved.