Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress
Background: Early life adversity is a risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex-bias in susceptibility, presentation, onset and severity, although mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to
... t contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes. Methods: To determine whether maternal docosahexanoic acid (DHA) supplementation effects offspring outcome following exposure to early prenatal stress (EPS), dams were fed nutritionally complete semi-purified diets that either contained adequate essential omega-6 (n-6) and omega-3 (n-3) fatty acids from corn and soy oils (control diet, CTL) or an experimental diet that was nutritionally-equivalent to the CTL diet, but contained 1% by weight DHA, a long-chain omega-3 fatty acid (22:6n-3). Dams were administered chronic variable stress during the first week of pregnancy (Embryonic day, E0.5 – 7.5). Developmental milestones were assessed at E 12.5. Results: Exposure to early prenatal stress (EPS) decreased placenta and embryo weight in males, but not females, exposed to CTL diet. DHA-enrichment reversed the sex-specific decrease in placenta and embryo weight following EPS. Early prenatal exposure upregulated expression of genes associated with oxygen and nutrient transport, including hypoxia inducible factor 3α (HIF3α), peroxisome proliferator-activated receptor alpha (PPARα), and insulin like growth binding factor 1 (IGFBP1), in placenta of CTL diet males exposed to EPS. DHA-enrichment in EPS-exposed animals abrogated male-specific upregulation of PPARα, HIF3α, and IGFBP1. Conclusions: This suggests that maternal dietary DHA enrichment may buffer against maternal stress programming of sex-specific outcomes during early development.