Maternal fish oil supplementation enhances nutrient transport in the placenta and milk biosynthesis in the mammary gland via the GPR120 signaling pathway.

INTRODUCTION: Maternal fish oil (FO) supplementation during pregnancy has been shown to improve pregnancy outcomes. FO is recognized as dietary source for n-3 polyunsaturated fatty acids (n-3 PUFAs). While early research has focused on the benefits of n-3 PUFAs for fetal neurodevelopment, retinal maturation and neonatal behavior, their roles in the placenta during late pregnancy and in the mammary gland during lactation still remain unknow. OBJECTIVES: Here, we aim to clarify the mechanisms by which maternal supplementation with FO during pregnancy and lactation affects placental and mammary gland function. METHODS: We evaluated the effects of FO on maternal placental nutrient transport, mammary gland milk synthesis and offspring growth. We then explored the molecular mechanisms by which docosahexaenoic acid (DHA) affects the biological function of placental trophoblast cells and mammary epithelial cells through in vitro experiments. Finally, a lipopolysaccharide-challenged experiment was performed to access the potential of maternal FO supplementation in alleviating offspring intestinal inflammation. RESULTS: Maternal supplementation with FO during late pregnancy increased offspring birth weight, associated with enhanced maternal placental vascularization and nutrient transporter abundance. Additionally, maternal FO supplementation during lactation improved milk biosynthesis, increasing the fat, protein, and non-fat solids content in both colostrum and mature milk, thereby promoting offspring growth. The stimulatory effects of DHA on nutrient transportation in placental trophoblast cells and nutrient secretion in mammary gland epithelial cells were mediated by GPR120 signaling pathways. Furthermore, maternal FO supplementation strengthened the placental barrier, reduced placental inflammation, oxidative stress and alleviated lipopolysaccharide-induced intestinal inflammation in offspring. CONCLUSION: Maternal FO supplementation during late pregnancy and lactation enhances offspring growth by increasing placental nutrient transport and milk biosynthesis, mediated by GPR120. Additionally, maternal FO supplementation reduces the susceptibility of offspring to intestinal inflammation.