Fetal glucocorticoid receptor (Nr3c1) deficiency alters the landscape of DNA methylation of murine placenta in a sex-dependent manner and is associated to anxiety-like behavior in adulthood.


Journal

Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664

Informations de publication

Date de publication:
17 01 2019
Historique:
received: 06 10 2018
accepted: 13 11 2018
entrez: 19 1 2019
pubmed: 19 1 2019
medline: 21 5 2019
Statut: epublish

Résumé

Prenatal stress defines long-term phenotypes through epigenetic programming of the offspring. These effects are potentially mediated by glucocorticoid release and by sex. We hypothesized that the glucocorticoid receptor (Gr, Nr3c1) fashions the DNA methylation profile of offspring. Consistent with this hypothesis, fetal Nr3c1 heterozygosity leads to altered DNA methylation landscape in fetal placenta in a sex-specific manner. There was a significant overlap of differentially methylated genes in fetal placenta and adult frontal cortex in Nr3c1 heterozygotes. Phenotypically, Nr3c1 heterozygotes show significantly more anxiety-like behavior than wildtype. DNA methylation status of fetal placental tissue is significantly correlated with anxiety-like behavior of the same animals in adulthood. Thus, placental DNA methylation might predict behavioral phenotypes in adulthood. Our data supports the hypothesis that Nr3c1 influences DNA methylation at birth and that DNA methylation in placenta correlates with adult frontal cortex DNA methylation and anxiety-like phenotypes.

Identifiants

pubmed: 30655507
doi: 10.1038/s41398-018-0348-7
pii: 10.1038/s41398-018-0348-7
pmc: PMC6336883
doi:

Substances chimiques

NR3C1 protein, mouse 0
Receptors, Glucocorticoid 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

23

Subventions

Organisme : CIHR
ID : MOP-42411
Pays : Canada

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Auteurs

Michaela Schmidt (M)

Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany. michaela.schmidt@zi-mannheim.de.

Elad Lax (E)

Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.
Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, H3G 1Y6, Canada.

Rudy Zhou (R)

Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.

David Cheishvili (D)

Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.
Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, H3G 1Y6, Canada.

Arne Mathias Ruder (AM)

Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.

Alessia Ludiro (A)

Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.

Florian Lapert (F)

Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.

Anna Macedo da Cruz (A)

Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.

Paolo Sandrini (P)

Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.

Teresa Calzoni (T)

Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.

Farida Vaisheva (F)

Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.

Christiane Brandwein (C)

Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.

Alessia Luoni (A)

Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.

Renaud Massart (R)

Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, H3G 1Y6, Canada.
Inserm, U894, Centre de Psychiatrie et Neurosciences, 75014, Paris, France.

Laurence Lanfumey (L)

Inserm, U894, Centre de Psychiatrie et Neurosciences, 75014, Paris, France.
Université Paris Descartes, UMRS894, 75014, Paris, France.

Marco Andrea Riva (MA)

Department of Pharmacological and Biomolecular Sciences, University of Milan, Via Balzaretti, 9, I-20133, Milan, Italy.

Michael Deuschle (M)

Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.

Peter Gass (P)

Central Institute of Mental Health Mannheim (ZI), Medical Faculty of Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.

Moshe Szyf (M)

Department of Pharmacology & Therapeutics, McGill University, Montreal, QC, H3G 1Y6, Canada.
Sackler Program for Epigenetics and Psychobiology, McGill University, Montreal, QC, H3G 1Y6, Canada.

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Classifications MeSH