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
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
23Subventions
Organisme : CIHR
ID : MOP-42411
Pays : Canada
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