Cited by 43Epigenetics and DNA MethylationMaternal Mental Health During Pregnancy and PostpartumGenetic Syndromes and Imprinting

Differential gene body methylation and reduced expression of cell adhesion and neurotransmitter receptor genes in adverse maternal environment

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Oh, J-e, Chambwe, N, Klein, S, Gal, J, Andrews, S, Gleason, G, Shaknovich, R, Melnick, A +2 more·2013·Translational Psychiatry

Abstract

Early life adversity, including adverse gestational and postpartum maternal environment, is a contributing factor in the development of autism, attention deficit hyperactivity disorder (ADHD), anxiety and depression but little is known about the underlying molecular mechanism. In a model of gestational maternal adversity that leads to innate anxiety, increased stress reactivity and impaired vocal communication in the offspring, we asked if a specific DNA methylation signature is associated with the emergence of the behavioral phenotype. Genome-wide DNA methylation analyses identified 2.3% of CpGs as differentially methylated (that is, differentially methylated sites, DMSs) by the adverse environment in ventral-hippocampal granule cells, neurons that can be linked to the anxiety phenotype. DMSs were typically clustered and these clusters were preferentially located at gene bodies. Although CpGs are typically either highly methylated or unmethylated, DMSs had an intermediate (20-80%) methylation level that may contribute to their sensitivity to environmental adversity. The adverse maternal environment resulted in either hyper or hypomethylation at DMSs. Clusters of DMSs were enriched in genes that encode cell adhesion molecules and neurotransmitter receptors; some of which were also downregulated, indicating multiple functional deficits at the synapse in adversity. Pharmacological and genetic evidence links many of these genes to anxiety.

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Crossref · 10.1038/tp.2012.130

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  • Oh et al. (176) found that adverse maternal environment induced DNA methylation changes in the offspring and the affected genes encode proteins involved in synapse formation and function (reduced expression of cell adhesion and neurotransmitter receptor genes was observed).

    “the authors found that adverse maternal environment induced DNA methylation changes in the offspring and the affected genes encode proteins involved in synapse formation and function (reduced expression of cell adhesion and neurotransmitter receptor genes was observed).”

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Authors
Oh, J.-E., Chambwe, N., Klein, S., Gal, J., Andrews, S., Gleason, G., Shaknovich, R., Melnick, A., Campagne, F., & Toth, M.
Affiliations
  • Weill Cornell Medicine (US)
  • Rockefeller University (US)
Corresponding author
Oh, J-e
Venue
Translational Psychiatry
Published
2013-01-22
Volume
3
Issue
1
Pages
e218-e218
ISSN
2158-3188 (ISSN-L)
OpenAlex
W2118987066
Cited by
43
References
69
Citations by year
2024: 1 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 7 · 2015: 8 · 2014: 5 · 2013: 1
FWCI
3.13
Type
journal article
Language
en
Open access
Locations
  • Translational Psychiatry (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
National Institute of Mental Health (R01MH058669, R01MH086883, 1R01-MH58669, R01MH094720)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
childhood adversity, DNA methylation, gene body methylation, differentially methylated sites, ventral hippocampus, granule cells, anxiety, adhesion molecules, neurotransmitter receptors, synapses, stress reactivity, vocal communication
MeSH terms
Animals, Anxiety, Cell Adhesion, Disease Models, Animal, Female, Male, Mice, Transgenic, Pregnancy, Prenatal Exposure Delayed Effects, Vocalization, Animal, Dentate Gyrus, CpG Islands, DNA Methylation, Epigenesis, Genetic, Receptor, Serotonin, 5-HT1A, Mice

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