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

Michaela Schmidt, Elad Lax, Rudy Zhou, David Cheishvili, Arne Mathias Ruder, Alessia Ludiro, Florian Lapert, Anna Macedo da Cruz, Paolo Sandrini, Teresa Calzoni, Farida Vaisheva, Christiane Brandwein, Alessia Luoni, Renaud Massart, Laurence Lanfumey, Marco Andrea Riva, Michael Deuschle, Peter Gass, Moshe Szyf

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number23
JournalTranslational Psychiatry
Volume9
Issue number1
DOIs
StatePublished - 1 Jan 2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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