Maternal Intake of n-3 Polyunsaturated Fatty Acids During Pregnancy Is Associated With Differential Methylation Profiles in Cord Blood White Cells

Abstract

A healthy diet during pregnancy is pivotal for the offspring health at birth and later in life. N-3 polyunsaturated fatty acids (n-3 PUFAs) are not endogenously produced in humans and are exclusively derived from the diet. They are pivotal for the fetus growth and neuronal development and seem beneficial in reducing the risk of cardiometabolic diseases and preventing later allergic disorders in the offspring by modulating the inflammatory immune response. In the present study, we investigated the association between maternal intakes of n-3PUFAs, profiled on maternal erythrocyte membranes at pregnancy term, and offspring DNA methylation on cord blood mononuclear cells in a sample of 118 mother–newborn pairs randomly drawn from the “Feeding fetus’ low-grade inflammation and insulin-resistance” study cohort. N-3 PUFA content on erythrocyte membranes is a validated biomarker to measure objectively medium term intake of n-3 PUFAs. Based on distribution of n-3 PUFA in the whole cohort of mothers, we identified mothers with low (n-3 PUFA concentration <25th percentile), medium (n-3 PUFAs between 25th and 75th percentiles), and high n-3 PUFA content (>75th percentile). The HumanMethylation450 BeadChip (Illumina) was used for the epigenome-wide association study using the Infinium Methylation Assay. The overall DNA methylation level was not different between the three groups while there was significant difference in methylation levels at certain sites. Indeed, 8,503 sites had significantly different methylations between low and high n-3 PUFA groups, 12,716 between low and medium n-3 PUFA groups, and 18,148 between high and medium n-3 PUFA groups. We found differentially methylated genes that belong prevalently to pathways of signal transduction, metabolism, downstream signaling of G protein-coupled receptors, and gene expression. Within these pathways, we identified four differentially methylated genes, namely, MSTN, IFNA13, ATP8B3, and GABBR2, that are involved in the onset of insulin resistance and adiposity, innate immune response, phospholipid translocation across cell membranes, and mechanisms of addiction to high fat diet, alcohol, and sweet taste. In conclusion, findings of this preliminary investigation suggest that maternal intake of n-3 PUFAs during pregnancy has potential to influence the offspring DNA methylation. Validation of results in a larger cohort and investigation of biological significance and impact on the phenotype are warranted.

Evidence for maternal diet-mediated effects on the offspring microbiome and immunity: implications for public health initiatives

“…Conversely, they found that high maternal fish intake was inversely associated with the development of eczema in 2-year-old offspring. Several other studies have found similar findings, including Calvani et al 16 , Romieu et al 17 and others 18 , 19 . Interestingly, a study which objectively evaluated maternal N-3 polyunsaturated fatty acid (PUFA) by determining N-3 PUFA levels on erythrocyte membranes found that high N-3 PUFA content was associated with differential patterns of methylation in the cord white blood cells of offspring 19 , suggesting a lasting epigenetic effect on the immune cells.…”

“…Several other studies have found similar findings, including Calvani et al 16 , Romieu et al 17 and others 18 , 19 . Interestingly, a study which objectively evaluated maternal N-3 polyunsaturated fatty acid (PUFA) by determining N-3 PUFA levels on erythrocyte membranes found that high N-3 PUFA content was associated with differential patterns of methylation in the cord white blood cells of offspring 19 , suggesting a lasting epigenetic effect on the immune cells. Another large prospective study from Japan 20 , The Osaka Maternal and Child Health Study, found that higher intake of n-6 polyunsaturated fatty acids of linoleic acid during pregnancy was independently related to an increase risk of eczema in infants aged 16–24 months, but not to the development of wheeze.…”

Perinatal and Early-Life Nutrition, Epigenetics, and Allergy

“…PUFA can induce epigenetic alterations both in vitro and in vivo [112][113][114]. For instance, perinatal maternal consumption of ω-linolenic acid correlates with the DNA methylation status of a gene encoding the mouse FA desaturase 2 (Fads2) in the livers of mothers and their progeny [115].…”

Current Insights on Early Life Nutrition and Prevention of Allergy

“…The T-helper shift from type 1 to type 2 may derive from a higher n-6: n-3 fatty acids ratio during pregnancy, leading to an increased risk of allergic rhinitis in offspring ( 6 ). It is thought that N-3 PUFAs probably limit cytokine cascade ( 7 ), decrease n-6 PUFA inflammatory effects, regulate T cell function (cell membrane fluidity, signaling, and gene transcription), and promote long-term effects through epigenetic mechanisms ( 8 ). Therefore, daily maternal supplementation of n-3 PUFAs could reduce the risk of food allergies and IgE-associated eczema in infants with a family history of allergy ( 9 ).…”