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

被引：21

作者：

Schmidt, Michaela ^{[1
]}

Lax, Elad ^{[2
,3
]}

Zhou, Rudy ^{[2
]}

Cheishvili, David ^{[2
,3
]}

Ruder, Arne Mathias ^{[1
]}

Ludiro, Alessia ^{[4
]}

Lapert, Florian ^{[1
]}

da Cruz, Anna Macedo ^{[1
]}

Sandrini, Paolo ^{[4
]}

Calzoni, Teresa ^{[4
]}

Vaisheva, Farida ^{[2
]}

Brandwein, Christiane ^{[1
]}

Luoni, Alessia ^{[4
]}

Massart, Renaud ^{[3
,5
]}

Lanfumey, Laurence ^{[5
,6
]}

Riva, Marco Andrea ^{[4
]}

Deuschle, Michael ^{[1
]}

Gass, Peter ^{[1
]}

Szyf, Moshe ^{[2
,3
]}

机构：

[1] Heidelberg Univ, Med Fac Mannhe, Cent Inst Mental Hlth Mannhe ZI, J5, D-68159 Mannheim, Germany

[2] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada

[3] McGill Univ, Sackler Program Epigenet & Psychobiol, Montreal, PQ H3G 1Y6, Canada

[4] Univ Milan, Dept Pharmacol & Biomol Sci, Via Balzaretti 9, I-20133 Milan, Italy

[5] Inserm, U894, Ctr Psychiat & Neurosci, F-75014 Paris, France

[6] Univ Paris 05, UMRS894, F-75014 Paris, France

来源：

TRANSLATIONAL PSYCHIATRY | 2019年 / 9卷 / 1期

关键词：

PRENATAL STRESS; PROGRAMS NEUROENDOCRINE; COGNITIVE FUNCTION; MATERNAL-BEHAVIOR; BDNF EXPRESSION; MALE-MICE; RESPONSES; GENE; HIPPOCAMPAL; RATS;

D O I：

10.1038/s41398-018-0348-7

中图分类号：

R749 [精神病学];

学科分类号：

100205 ;

摘要：

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.

引用

页数：11

共 13 条

[1] 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
Translational Psychiatry, 9
[2] Microglial Nr3c1 Depletion Alters Stress Effects on Synaptic Density and Behavior in a Sex-Dependent Manner
Vollmer, Lauren
Mueller, Etienne
Bollinger, Justin
Gonzalez, Rosa
Robinson, J. Elliott
Wohleb, Eric
NEUROPSYCHOPHARMACOLOGY, 2023, 48 : 192 - 193
[3] Methylation of the Glucocorticoid Receptor (NR3C1) in Placenta Is Associated with Infant Cry Acoustics
Sheinkopf, Stephen J.
Righi, Giulia
Marsit, Carmen J.
Lester, Barry M.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE, 2016, 10
[4] Maternal anxiety and depression in pregnancy and DNA methylation of the NR3C1 glucocorticoid receptor gene
Dereix, Alexandra E.
Ledyard, Rachel
Redhunt, Allyson M.
Bloomquist, Tessa R.
Brennan, Kasey Jm
Baccarelli, Andrea A.
Hacker, Michele R.
Burris, Heather H.
EPIGENOMICS, 2021, 13 (21) : 1701 - 1709
[5] The sex-dependent role of the glucocorticoid receptor in depression: variations in the NR3C1 gene are associated with major depressive disorder in women but not in men
Sarubin, Nina
Hilbert, Sven
Naumann, Felix
Zill, Peter
Wimmer, Anna-Maria
Nothdurfter, Caroline
Rupprecht, Rainer
Baghai, Thomas C.
Buehner, Markus
Schuele, Cornelius
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, 2017, 267 (02) : 123 - 133
[6] The sex-dependent role of the glucocorticoid receptor in depression: variations in the NR3C1 gene are associated with major depressive disorder in women but not in men
Nina Sarubin
Sven Hilbert
Felix Naumann
Peter Zill
Anna-Maria Wimmer
Caroline Nothdurfter
Rainer Rupprecht
Thomas C. Baghai
Markus Bühner
Cornelius Schüle
European Archives of Psychiatry and Clinical Neuroscience, 2017, 267 : 123 - 133
[7] MODERATE PRENATAL ALCOHOL EXPOSURE ALTERS CRFR1-REGULATED GABA RELEASE AND ANXIETY-LIKE BEHAVIOR IN A SEX-DEPENDENT MANNER IN ADOLESCENT RATS
Rouzer, S. K.
Diaz, M. R.
ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH, 2021, 45 : 91A - 91A
[8] Mismatched Prenatal and Postnatal Maternal Depressive Symptoms and Child Behaviours: A Sex-Dependent Role for NR3C1 DNA Methylation in the Wirral Child Health and Development Study
Hill, Jonathan
Pickles, Andrew
Wright, Nicola
Quinn, John P.
Murgatroyd, Chris
Sharp, Helen
CELLS, 2019, 8 (09)
[9] Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD
Lewis, Candace R.
Tafur, Joseph
Spencer, Sophie
Green, Joseph M.
Harrison, Charlotte
Kelmendi, Benjamin
Rabin, David M.
Yehuda, Rachel
Yazar-Klosinski, Berra
Cahn, Baruch Rael
FRONTIERS IN PSYCHIATRY, 2023, 14
[10] Prenatal earthquake stress exposure in different gestational trimesters is associated with methylation changes in the glucocorticoid receptor gene (NR3C1) and long-term working memory in adulthood
Ran Wang
Jincheng Wang
Shuqi Xu
Lan Wang
Mei Song
Cuixia An
Xueyi Wang
Translational Psychiatry, 12

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