Maternal dietary n-3 PUFA deficiency leads to sex-specific alterations in placental and cerebral fatty acid profiles and in oxylipin profiles in the developing mouse brain

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), are essential for optimal neurodevelopment through their effect on neuronal proliferation, neurite outgrowth and synaptogenesis. Emerging evidence highlights that brain PUFAs are metabolized in oxylipins, the bioactive oxidized PUFA metabolites known to regulate inflammatory processes. Recent data highlighted that both PUFA and oxylipin profiles are modulated in the brains of adult male mice by dietary PUFA content. However, little is known on the impact of maternal dietary n-3 PUFA intake during the perinatal period and the neurodevelopmental profile of brain fatty acids and associated oxylipins in mouse offspring, and whether these effects differ between sexes. To address this question, we first measured fatty acid levels in the placenta and embryonic brain of male and female mice at embryonic day (E)17.5 of mothers fed an n-3 PUFA-sufficient diet (based on canola oil, rich in the n-3 precursor alpha-linolenic acid) or an n-3 PUFA-deficient diet (based on sunflower oil, rich in the n-6 precursor linoleic acid) in n-3 PUFAs starting at E0. Then, fatty acids and oxylipins were measured at different post-natal stages, in the brain at postnatal day (P)0 and P7, and in the hippocampus at P14 and P21, in both male and female mouse offspring. Our results show that maternal n-3 PUFA dietary deficiency alters fatty acid profiles as early as E17.5 in both the placenta and the brain. Furthermore, dietary intervention affects both fatty acid and oxylipin profiles throughout postnatal brain development, with notable sex-specific differences. These findings highlight the importance of maternal n-3 PUFA intake during the perinatal period for establishing and maintaining PUFA and oxylipin profiles in the developing brain.