Epigenetic Modifications Associated with Maternal Anxiety during Pregnancy and Children's Behavioral Measures.

Lei Cao-Lei,Matthias Platzer,Marion I Van Den Heuvel,Marijke A K A Braeken,Matthias Schwab,Guillaume Elgbeili,Renée A Otte,Bea R H Van Den Bergh,Otto W Witte,Klaus Huse

doi:10.3390/cells10092421

Abstract

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.

Highlights

This article is an open access articleWith the population aging worldwide, understanding the biology of healthy aging is more relevant than ever
The current study prospectively investigated whether maternal anxiety during pregnancy could influence children’s behavioral measures through epigenetic mechanisms
For IGF2/H19 imprinted control region (ICR), we found a negative association between maternal anxiety and methylation levels in boys (Figure 3A–C), in contrast to a positive association in girls

Summary

Introduction

This article is an open access articleWith the population aging worldwide, understanding the biology of healthy aging is more relevant than ever. The relationship between adverse environmental influences during critical periods of prenatal life and the health of offspring in later life is the basis of the ‘Fetal Programming’ or ‘Developmental Origins of Health and Disease (DOHaD) hypothesis’ [6]. Exposure to maternal distress during pregnancy—including the experience of anxiety, of depression or of stressful events—is a rather common environmental challenge for the fetus. The prevalence of depression is up to 10% [12] or 7.4% (95% CIs: 2.2, 12.6), 12.8% (95% CIs: 10.7, 14.8), and 12.0% (95% CIs: 7.4, 16.7) for each trimester, respectively [13]. Higher percentages for depression (pooled prevalence of 25.5% in 37 studies (n = 47,677)) and anxiety (pooled prevalence of 30.5% in 34 studies (n = 42,773)) occur during periods of universal stress exposure, such as the corona pandemic [14]. Boekhorst et al [15] reported a 49.7%

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