Epigenetic changes are associated with altered behavior and neuropsychiatric disorders and they modify the trajectory of aging. Maternal anxiety during pregnancy is a common environmental challenge for the fetus, causing changes in DNA methylation. Here, we determined the mediating role of DNA methylation and the moderating role of offspring sex on the association between maternal anxiety and children’s behavioral measures. In 83 mother–child dyads, maternal anxiety was assessed in each trimester of pregnancy when the child was four years of age. Children’s behavioral measures and children’s buccal DNA methylation levels (NR3C1, IGF2/H19 ICR, and LINE1) were examined. Higher maternal anxiety during the third trimester was associated with more methylation levels of the NR3C1. Moderating effects of sex on the association between maternal anxiety and methylation were found for IGF2/H19 and LINE1 CpGs. Mediation analysis showed that methylation of NR3C1 could buffer the effects of maternal anxiety on children’s behavioral measures, but this effect did not remain significant after controlling for covariates. In conclusion, our data support an association between maternal anxiety during pregnancy and DNA methylation. The results also underscore the importance of sex differences and timing effects. However, DNA methylation as underlying mechanism of the effect of maternal anxiety during pregnancy on offspring’s behavioral measures was not supported.

Exposure to stress during pregnancy may program susceptibility to the development of obesity in offspring. Our goal was to determine whether prenatal maternal stress (PNMS) due to a natural disaster was associated with child obesity, and to compare the DNA methylation profiles in obese versus non-obese children at age 13½ years. Women and their children were involved in the longitudinal natural disaster study—Project Ice Strom, which served as a human model to study PNMS. Blood was collected from 31 children (including five obese children). Infinium HumanMethylation450 BeadChip Array was performed for genome-wide DNA methylation analyses. Results demonstrated a well-defined obesity-associated genome-wide DNA methylation pattern. There were 277 CpGs, corresponding to 143 genes, were differentially-methylated. IPA analyses revealed 51 canonical pathways, and enrichment of pathways was involved in immune function. Although no significant association was found between PNMS and child obesity, the preliminary data in the study revealed obesity-associated methylation patterns on a genome-wide level in children.

The potent neurotoxicity of benzo[a]pyrene (B[a]P) has been suggested to be a susceptibility factor accelerating the onset of brain tumours and the emergence of neurobehavioural disturbances. B[a]P has been shown to be neurotoxic, acting directly on both the central and peripheral nervous systems, as well as indirectly via peripheral organs like liver and gut. By using a realistic B[a]P exposure scenario (0.02–200 mg/kg/day, 10 days) in mice, we elucidated brain-specific B[a]P metabolism and at identified hydroxylated B[a]P metabolites in serum which could be used as markers of cognitive impairment. Repeated oral administration of B[a]P led to, at the doses of 20 and 200 mg/kg/day, significant overexpression of Cyp1a1/Cyp1b1 in 2 out of the 3 brain regions considered, thereby suggesting the ability of the brain to metabolize B[a]P itself. At the same doses, mice exhibited a reduction in anxiety in both the elevated plus maze and the hole board apparatus. Concomitantly, B[a]P triggered dose-dependent changes in Nmda subunit expression (Nr1 and Nr2a/Nr2b) in areas involved in cognition. We detected 9-OH-B[a]P and 7,8-diol-B[a]P in serum at the level for which cognitive impairment was observed. We suggest that these metabolites may, in the future be exploited as potent biomarkers of B[a]P-induced cognitive impairments.