Effect of gestational hypercholesterolemia and maternal immunization on offspring plasma eicosanoids.

Abstract

Maternal immunization with oxidized low-density lipoprotein prior to pregnancy prevents pathogenic in utero programming by gestational hypercholesterolemia, but it is unknown whether gestational hypercholesterolemia and maternal immunization affect similar pathways. A lipidomic approach was used for unbiased plasma eicosanoid profiling in adult offspring of immunized and nonimmunized normocholesterolemic or hypercholesterolemic rabbit mothers. Gestational hypercholesterolemia was associated with increased levels of some eicosanoids formed by the cyclooxygenase and 12-lipoxygenase pathways only (including thromboxane B2, prostaglandin [PG] F2α, PGE2, and PGD2). Immunization of hypercholesterolemic or normocholesterolemic mothers reduced 9 of 14 eicosanoids of the cyclooxygenase pathway, 21 of 23 eicosanoids of the 5- and 12-lipoxygenase pathways (eg, 5-hydroxyeicosatetraenoic acid, hepoxilin B3, 12-hydroxyeicosatetraenoic acid), 8 of 19 eicosanoids of the cytochrome P-450 pathway, and all metabolites of the nonenzymatic pathway. Maternal immunization not only counteracts in utero programming by gestational hypercholesterolemia but reduces a broad range of eicosanoid modulators of immunity and inflammation in offspring.