Introduction: Maternal obesity is a risk factor for cardiometabolic and immune-related diseases in the offspring after birth. Monocytes from offspring born to obese women have an impaired function that could result from abnormal DNA methylation patterns associated with maternal obesity. The aim of this study was to determine changes in DNA methylation in monocytes from offspring born to obese women and to evaluate the potential effects of such epigenetic changes in immune function.
Methods: Cord blood samples were obtained from healthy term newborns, matched by birthweight and gestational age, born to lean (n = 12) and obese women (n = 15). Genome-wide differentially methylated CpGs (DMC) were determined using an Infinium MethylationEPIC BeadChip (850K). Functional analysis for DMC was performed using DAVID, and the potential effect on gene expression was validated with data from The Cancer Genome Atlas (TCGA) database.
Results: DNA methylation analysis revealed 22,313 DMC in monocytes of female offspring of obese women (FO) (adjusted p < 0.01 with FDR < 0.05), and 20,412 DMC (nominal p < 0.01) in male newborns that lost significance after FDR correction. Functional analysis of genes with hypermethylated CpG located in promoter regions showed an enrichment of immune-related processes and pathways in FO monocytes. TCGA data showed that many of these DMCs were negatively correlated to gene expression suggesting a suppression of monocyte function through DNA methylation. Also, a variety of genes involved in the canonical and alternative NF-κB pathway, a major regulator of inflammation, are differentially methylated in FO monocytes.
Conclusions: Maternal obesity might program in a sex-specific manner the innate immune function through an altered DNA methylation pattern. These epigenetic changes occur at immune-related genes and may account for the impaired function of monocytes in female offspring.
Funded by Fondecyt 1181341