Maternal n-3 PUFA deficiency alters brain fatty acid and oxylipin profiles across perinatal development in offspring

Marchaland, F.; Martinat, M.; Di Miceli, M.; Gregoire, S.; Rossitto, M.; Morel, L.; Aubert, A.; Sere, A.; Delpech, J.-C.; Joffre, C.; Acar, N.; Bazinet, R. P.; Laye, S.

doi:10.1101/2025.11.02.686109

bioRxiv · 10.1101/2025.11.02.686109

Maternal n-3 PUFA deficiency alters brain fatty acid and oxylipin profiles across perinatal development in offspring

Marchaland, F.·Martinat, M.·Di Miceli, M.·Gregoire, S.·Rossitto, M.·Morel, L.·Aubert, A.·Sere, A.·Delpech, J.-C.·Joffre, C.·Acar, N.·Bazinet, R. P.·Laye, S.

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Abstract

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 adult male brain 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 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 offspring of mothers fed a sufficient or deficient diet in n-3 PUFAs at embryonic day (E)17.5. Then, fatty acids and oxylipins were measured at different post-natal stages, in the brain at P0 and P7, and in the hippocampus at P14 and P21, in both male and female 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 underscore the critical importance of adequate maternal n-3 PUFA intake during the perinatal period for maintaining an optimal PUFA and oxylipin profiles, with potential implications for fetal and postnatal brain development.

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Marchaland, F., Martinat, M., Di Miceli, M., Gregoire, S., Rossitto, M., Morel, L., Aubert, A., Sere, A., Delpech, J.-C., Joffre, C., Acar, N., Bazinet, R. P., Laye, S.. 2025-11-04. Maternal n-3 PUFA deficiency alters brain fatty acid and oxylipin profiles across perinatal development in offspring. https://doi.org/10.1101/2025.11.02.686109

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