DNA methylation profiles in the blood of newborn term infants born to mothers with obesity

Abstract

Maternal obesity is an important risk factor for childhood obesity and influences the prevalence of metabolic diseases in offspring. As childhood obesity is influenced by postnatal factors, it is critical to determine whether children born to women with obesity during pregnancy show alterations that are detectable at birth. Epigenetic mechanisms such as DNA methylation modifications have been proposed to mediate prenatal programming. We investigated DNA methylation signatures in male and female infants from mothers with a normal Body Mass Index (BMI 18.5–24.9 kg/m2) compared to mothers with obesity (BMI≥30 kg/m2). BMI was measured during the first prenatal visit from women recruited into the Ontario Birth Study (OBS) at Mount Sinai Hospital in Toronto, ON, Canada. DNA was extracted from neonatal dried blood spots collected from heel pricks obtained 24 hours after birth at term (total n = 40) from women with a normal BMI and women with obesity matched for parity, age, and neonatal sex. Reduced representation bisulfite sequencing was used to identify genomic loci associated with differentially methylated regions (DMRs) in CpG-dense regions most likely to influence gene regulation. DMRs were predominantly localized to intergenic regions and gene bodies, with only 9% of DMRs localized to promoter regions. Genes associated with DMRs were compared to those from a large publicly available cohort study, the Avon Longitudinal Study of Parents and Children (ALSPAC; total n = 859). Hypergeometric tests revealed a significant overlap in genes associated with DMRs in the OBS and ALSPAC cohorts. PTPRN2, a gene involved in insulin secretion, and MAD1L1, which plays a role in the cell cycle and tumor suppression, contained DMRs in males and females in both cohorts. In males, KEGG pathway analysis revealed significant overrepresentation of genes involved in endocytosis and pathways in cancer, including IGF1R, which was previously shown to respond to diet-induced metabolic stress in animal models and in lymphocytes in the context of childhood obesity. These preliminary findings are consistent with Developmental Origins of Health and Disease paradigm, which posits that adverse prenatal exposures set developmental health trajectories.

Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity

“…Others have reported placental LPL gene methylation is associated with CB lipid profiles [36] and anthropometric profiles in children at age 5 [37], and adipose tissue lipoprotein lipase (LPL) is associated with metabolic syndrome in adults [38], supporting that LPL may be regulated by DNAme and linked to metabolic disease. Lastly, we observed association of maternal triglycerides with DNAme near PTPRN2, similar to results in offspring from mothers with obesity compared with normal weight from both the Ontario Birth Cohort and Avon Studies [39].…”

SARS-CoV-2 Covid-19 Infection During Pregnancy and Differential DNA Methylation in Human Cord Blood Cells From Term Neonates

“…Our study, however, also has several limitations, for example, the sample size of 16 neonates is small, but similar limited sample sizes have been used in studies investigating differential DNA methylation patterns. 63,64 There is an inherent chance of finding differences in the DNA methylation due to multiple comparison and our results should be considered as being hypothesis generating and should be validated in a larger cohort.…”

Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders

“…This approach has been used to examine maternal smoking (94–97) glucocorticoid, and prenatal folate exposure during pregnancy (55,98), alongside environmental exposures such as pollution (98). Examining DNAm proxies of inflammation is uncommon, but given the health associations with inflammatory-related DNAm in adult cohorts (47,48,99), and the shared nature of epigenetic changes between mother and infants (64,100), we hypothesised that variance in the neonatal methylome could reflect a convergence of amassed inflammatory burden from different perinatal origins.…”