The effect of perinatal supplementation of DHA on specialized pro-resolving lipid mediators in the brain of offspring

Abstract

The perinatal period is crucial for fetal neurological development, relying on omega-3 polyunsaturated fatty acids (PUFAs) for essential processes. Omega-3 PUFA, including docosahexaenoic acid (DHA), are precursors to a novel class of bioactive metabolites called specialized pro-resolving mediators (SPMs), which have been suggested to have a dual purpose in mitigating neuroinflammation while simultaneously supporting cognitive outcomes, implicating a role in offspring neurodevelopment. DHA is evidenced for its role in early brain development, but the underlying mechanism it exerts its cognitive benefits remain unclear. Pregnant sows were fed a control diet (CON; n = 6) or a diet with DHA (n = 6, 75 mg DHA/kg BW/day) from gestation through lactation. At weaning, piglets (n = 2/sow) underwent resting state-functional magnetic resonance imaging (rs-fMRI) to assess brain functional activation. Subsequently, brain tissue from prefrontal cortex, cerebellum, and hippocampus were collected from piglets. Tissue DHA and eicosapentaenoic acid (EPA)-derived SPMs were quantified using LC-MS. Levels of SPMs were higher in the brains of piglets from DHA-fed sows, particularly in the prefrontal cortex and cerebellum, compared to control piglets. Additionally, a distinct association of several prefrontal SPMs with activation of the cerebellar functional network was marked in the piglet offspring. The findings highlight a potential for SPMs to function as mediators for neurodevelopmental programming, through contributing to inflammation resolution and neuronal connectivity. This work underscores the importance of maternal nutrition in shaping offspring brain health and lays the groundwork for targeted interventions leveraging the benefits of DHA and its bioactive metabolites.