DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project Ice Storm.

Lei Cao-Lei,David P Laplante,Guillaume Elgbeili,Moshe Szyf,Franz Veru,Suzanne King

doi:10.1186/s13148-016-0219-0

Abstract

BackgroundPrenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. We tested here the hypothesis that DNA methylation of genes in the NF-κB signaling pathway in T cells mediates the effect of objective PNMS on Th1 and Th2 cytokine production in blood from 13½ year olds who were exposed in utero to the 1998 Quebec ice storm.ResultsBootstrapping analyses were performed with 47 CpGs across a selection of 20 genes for Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-4 and IL-13). Six CpGs in six different NF-κB signaling genes (PIK3CD, PIK3R2, NFKBIA, TRAF5, TNFRSF1B, and LTBR) remained as significant negative mediators of objective PNMS on IFN-γ secretion after correcting for multiple comparisons. However, no mediation effects on IL-2, IL-4 and IL-13 survived Bonferroni correction.ConclusionsThe present study provides preliminary evidence supporting the mediating role of DNA methylation in the association between objective aspects of PNMS and child immune states, favoring a Th2 shift.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-016-0219-0) contains supplementary material, which is available to authorized users.

Highlights

Prenatal maternal stress (PNMS) is an important programming factor of postnatal immunity
One cannot extrapolate the effects of stress on the fully developed adult immune system to the effects of maternal stress on the unborn child, due to the physiological changes occurring in stress physiology during pregnancy [8], the dynamic shielding from the maternal environment that the placenta provides to the fetus [9], and the developmental stage [10] of the immune system at the time of exposure to PNMS
Since DNA methylation levels were obtained from T cells, we focused on exploring the potential mediation effect of DNA methylation on Th1- and Th2-type cytokine secretion

Summary

Introduction

Prenatal maternal stress (PNMS) is an important programming factor of postnatal immunity. One cannot extrapolate the effects of stress on the fully developed adult immune system to the effects of maternal stress on the unborn child, due to the physiological changes occurring in stress physiology during pregnancy [8], the dynamic shielding from the maternal environment that the placenta provides to the fetus [9], and the developmental stage [10] of the immune system at the time of exposure to PNMS Despite these considerations, PNMS has demonstrated a pervasive influence on immunity per se, altering a broad array of functions at the molecular and cellular levels.

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