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 non-immunized normo- or hypercholesterolemic rabbit mothers.
Gestational hypercholesterolemia was associated with increased levels of some eicosanoids formed by the cyclooxygenase and 12-lipoxygenase pathways only (including TXB2, PGF2α, 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 (e.g. 5-HETE, HXB3, 12-HETE), 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.