Maternal PUFAs, Placental Epigenetics, and Their Relevance to Fetal Growth and Brain Development

Dietary polyunsaturated fatty acids (PUFAs), especially omega-3 (n-3) and n-6 long-chain (LC) PUFAs, are indispensable for the fetus' brain supplied by the placenta. Despite being highly unsaturated, n-3 LCPUFA-docosahexaenoic acid (DHA) plays a protective role as an antioxidant in the brain. Deficiency of DHA during fetal development may cause irreversible damages in neurodevelopment programming. Dietary PUFAs can impact placental structure and functions by regulating early placentation processes, such as angiogenesis. They promote remodeling of uteroplacental architecture to facilitate increased blood flow and surface area for nutrient exchange. The placenta's fatty acid transfer depends on the uteroplacental vascular development, ensuring adequate maternal circulatory fatty acids transport to fulfill the fetus' rapid growth and development requirements. Maternal n-3 PUFA deficiency predominantly leads to placental epigenetic changes than other fetal developing organs. A global shift in DNA methylation possibly transmits epigenetic instability in developing fetuses due to n-3 PUFA deficiency. Thus, an optimal level of maternal omega-3 (n-3) PUFAs may protect the placenta's structural and functional integrity and allow fetal growth by controlling the aberrant placental epigenetic changes. This narrative review summarizes the recent advances and underpins the roles of maternal PUFAs on the structure and functions of the placenta and their relevance to fetal growth and brain development.