Abstract

Mothers provide essential nutrients, including docosahexaenoic acid (DHA), an omega-3 fatty acid, during the perinatal period. DHA deficiency in perinatal mothers is linked to developmental abnormalities, especially in the central nervous system of the offspring; however, its specific impact on distinct events in fetal and neonatal brain development and prospective brain functions remains incompletely understood. We demonstrated using mice lacking Agpat3, a gene encoding the enzyme that synthesizes DHA-containing phospholipids (DHA-PLs), that maternal DHA-PL synthesis significantly contributes to the maternal- offspring DHA supply during the fetal period but not in infancy. Selective modulation of DHA-PL levels during fetal and postnatal periods in Agpat3-knockout mice showed that fetal stage-specific insufficiency in maternal DHA-PL supply potentially influences the neuropsychiatric phenotype in adult mice without affecting postnatal tissue DHA-PL levels, weight gain, and brain expansion. Collectively, enhancing maternal DHA-PL synthesis during pregnancy may help prevent prospective neuropsychiatric abnormalities in the offspring.