Prenatal maternal stress and wheeze in children: novel insights into epigenetic regulation

Psychological stress during pregnancy increases the risk of childhood wheeze and asthma. However, the transmitting mechanisms remain largely unknown. Since epigenetic alterations have emerged as a link between perturbations in the prenatal environment and an increased disease risk we used whole geno...

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Published in:Scientific reports 2016-06, Vol.6 (1), p.28616-28616, Article 28616
Main Authors: Trump, Saskia, Bieg, Matthias, Gu, Zuguang, Thürmann, Loreen, Bauer, Tobias, Bauer, Mario, Ishaque, Naveed, Röder, Stefan, Gu, Lei, Herberth, Gunda, Lawerenz, Christian, Borte, Michael, Schlesner, Matthias, Plass, Christoph, Diessl, Nicolle, Eszlinger, Markus, Mücke, Oliver, Elvers, Horst-Dietrich, Wissenbach, Dirk K., von Bergen, Martin, Herrmann, Carl, Weichenhan, Dieter, Wright, Rosalind J., Lehmann, Irina, Eils, Roland
Format: Article
Language:English
Subjects:
45/77
631/337/176/1988
692/308/174
Asthma
Children & youth
Deoxyribonucleic acid
Disease
DNA
DNA methylation
Epigenetics
Fetuses
Genetic testing
Genomes
Health risks
Humanities and Social Sciences
Mothers
multidisciplinary
Pharmacy
Pregnancy
Science
Science (multidisciplinary)
Stress
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Summary:Psychological stress during pregnancy increases the risk of childhood wheeze and asthma. However, the transmitting mechanisms remain largely unknown. Since epigenetic alterations have emerged as a link between perturbations in the prenatal environment and an increased disease risk we used whole genome bisulfite sequencing (WGBS) to analyze changes in DNA methylation in mothers and their children related to prenatal psychosocial stress and assessed its role in the development of wheeze in the child. We evaluated genomic regions altered in their methylation level due to maternal stress based of WGBS data of 10 mother-child-pairs. These data were complemented by longitudinal targeted methylation and transcriptional analyses in children from our prospective mother-child cohort LINA for whom maternal stress and wheezing information was available (n = 443). High maternal stress was associated with an increased risk for persistent wheezing in the child until the age of 5. Both mothers and children showed genome-wide alterations in DNA-methylation specifically in enhancer elements. Deregulated neuroendocrine and neurotransmitter receptor interactions were observed in stressed mothers and their children. In children but not in mothers, calcium- and Wnt-signaling required for lung maturation in the prenatal period were epigenetically deregulated and could be linked with wheezing later in children’s life.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep28616