Abstract

BackgroundPrenatal maternal stress (PNMS) predicts a wide variety of behavioral and physical outcomes in the offspring. Although epigenetic processes may be responsible for PNMS effects, human research is hampered by the lack of experimental methods that parallel controlled animal studies. Disasters, however, provide natural experiments that can provide models of prenatal stress.MethodsFive months after the 1998 Quebec ice storm we recruited women who had been pregnant during the disaster and assessed their degrees of objective hardship and subjective distress. Thirteen years later, we investigated DNA methylation profiling in T cells obtained from 36 of the children, and compared selected results with those from saliva samples obtained from the same children at age 8.ResultsPrenatal maternal objective hardship was correlated with DNA methylation levels in 1675 CGs affiliated with 957 genes predominantly related to immune function; maternal subjective distress was uncorrelated. DNA methylation changes in SCG5 and LTA, both highly correlated with maternal objective stress, were comparable in T cells, peripheral blood mononuclear cells (PBMCs) and saliva cells.ConclusionsThese data provide first evidence in humans supporting the conclusion that PNMS results in a lasting, broad, and functionally organized DNA methylation signature in several tissues in offspring. By using a natural disaster model, we can infer that the epigenetic effects found in Project Ice Storm are due to objective levels of hardship experienced by the pregnant woman rather than to her level of sustained distress.

Highlights

  • Prenatal maternal stress (PNMS) predicts a wide variety of outcomes in the offspring [1]

  • Storm32 scores ranged from 5–21 (Mean = 10.9, SD = 4.2) and Impact of Events Scale-Revised (IES-R) scores ranged from 0–40 (Mean = 9.5, SD = 9.2)

  • No statistically significant correlations were found between subjective PNMS (IES-R) and methylation levels for any CGs

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Summary

Introduction

Prenatal maternal stress (PNMS) predicts a wide variety of outcomes in the offspring [1]. Experimental research with non-human primates shows that in utero exposure to even mild stressors can produce permanent changes in metabolic, immune and behavioral systems in the fetus [4,5]. Retrospective epidemiological studies show that severe PNMS in humans, such as that caused by military invasion, increases risk for a variety of disorders in the offspring including schizophrenia [6]. Prospective human studies suggest that maternal anxiety and life events in pregnancy predict the fetus’ risk for cognitive and behavioral problems in later life [7]. Prenatal maternal stress (PNMS) predicts a wide variety of behavioral and physical outcomes in the offspring. Provide natural experiments that can provide models of prenatal stress

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