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

doi:10.1038/s41398-018-0348-7

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 journal › Article › peer-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 language	English
Article number	23
Journal	Translational Psychiatry
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41398-018-0348-7
State	Published - 1 Jan 2019
Externally published	Yes

All Science Journal Classification (ASJC) codes

Psychiatry and Mental health
Cellular and Molecular Neuroscience
Biological Psychiatry

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10.1038/s41398-018-0348-7

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Schmidt, M., Lax, E., Zhou, R., Cheishvili, D., Ruder, A. M., Ludiro, A., Lapert, F., Macedo da Cruz, A., Sandrini, P., Calzoni, T., Vaisheva, F., Brandwein, C., Luoni, A., Massart, R., Lanfumey, L., Riva, M. A., Deuschle, M., Gass, P., & Szyf, M. (2019). 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. Translational Psychiatry, 9(1), Article 23. https://doi.org/10.1038/s41398-018-0348-7

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title = "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",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = jan,

day = "1",

doi = "10.1038/s41398-018-0348-7",

language = "الإنجليزيّة",

volume = "9",

journal = "Translational Psychiatry",

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Schmidt, M, Lax, E, Zhou, R, Cheishvili, D, Ruder, AM, Ludiro, A, Lapert, F, Macedo da Cruz, A, Sandrini, P, Calzoni, T, Vaisheva, F, Brandwein, C, Luoni, A, Massart, R, Lanfumey, L, Riva, MA, Deuschle, M, Gass, P & Szyf, M 2019, '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', Translational Psychiatry, vol. 9, no. 1, 23. https://doi.org/10.1038/s41398-018-0348-7

TY - JOUR

T1 - 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

AU - Schmidt, Michaela

AU - Lax, Elad

AU - Zhou, Rudy

AU - Cheishvili, David

AU - Ruder, Arne Mathias

AU - Ludiro, Alessia

AU - Lapert, Florian

AU - Macedo da Cruz, Anna

AU - Sandrini, Paolo

AU - Calzoni, Teresa

AU - Vaisheva, Farida

AU - Brandwein, Christiane

AU - Luoni, Alessia

AU - Massart, Renaud

AU - Lanfumey, Laurence

AU - Riva, Marco Andrea

AU - Deuschle, Michael

AU - Gass, Peter

AU - Szyf, Moshe

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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DO - 10.1038/s41398-018-0348-7

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SN - 2158-3188

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JO - Translational Psychiatry

JF - Translational Psychiatry

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ER -

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

Abstract

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