Validation of an ovine model for studying impacts of prenatal docosahexaenoic acid supplementation on fetal tissue membrane composition and metabolism.

Dietary supplementation with long-chain omega-3 fatty acids such as docosahexaenoic acid (DHA) is recommended to women during pregnancy to prevent preterm birth and support optimal fetal development. DHA supplementation also decreases circulating triglyceride levels through diverse effects on systemic lipid metabolism, but its impacts on fetal metabolism are largely unknown due to inherent limitations of such investigations during pregnancy. The aim of the present study was to validate a large animal model suitable for investigating impacts of prenatal DHA supplementation on fetal development and metabolism. White-faced ewes were fed either a control diet (Show-rite NewCo Lamb Feed) or a DHA-supplemented diet (control diet + 3% algae-derived DHA) from 2-3 weeks before pregnancy until mid-gestation (75 days), after which serum, placenta and fetal tissues were collected for biochemical analysis of phospholipid fatty acid composition and fatty acid transporter expression, and a broader characterization of nutrient metabolism of fetal heart, skeletal muscle, and liver. Prenatal DHA supplementation reduced maternal serum triglycerides and significantly enriched all six fetal tissues examined. These results were paralleled by tissue-specific impacts on fetal fatty acid transporters and metabolism, a greater capacity of fetal muscle and heart to oxidize lipids over carbohydrate substrates, and reduced expression of insulin receptor substrate-1 in fetal muscle and liver. In conclusion, this study demonstrates the utility of an ovine model for investigating the biological effects of prenatal DHA supplementation on fetal development and metabolism, and highlights the need for a better understanding of its impacts on fetal and offspring metabolic health trajectory.