Evidence map›Paper›PMID 24976947›Full record

ArticleBiology of sex differences2014

The effects of perinatal testosterone exposure on the DNA methylome of the mouse brain are late-emerging.

Negar M Ghahramani, Tuck C Ngun, Pao-Yang Chen, Yuan Tian, Sangitha Krishnan, Stephanie Muir, Liudmilla Rubbi, Arthur P Arnold, Geert J de Vries, Nancy G Forger and 2 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of sex differences, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
7.3field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

73 citing papers in PubMed, 123 citations in OpenAlex.

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  13. The Role of Transposable Elements in Sexual Development.Frontiers in behavioral neuroscience · 2022
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  16. Perinatal activation of ERJournal of neurophysiology · 2021
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13 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 2 countries.

Negar M Ghahramani *Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Tuck C Ngun *Department of Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Pao-Yang ChenInstitute of Plant and Microbial Biology, Academia Sinica, Taipei 11529, Taiwan.
Yuan TianInterdepartmental PhD Program in Bioinformatics, UCLA, Los Angeles, CA 90095, USA.
Sangitha KrishnanDepartment of Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Stephanie MuirDepartment of Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
Liudmilla RubbiDepartment of Molecular, Cellular, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
Arthur P ArnoldLaboratory of Neuroendocrinology of the Brain Research Institute, UCLA, Los Angeles, CA 90095, USA.
Geert J de VriesNeuroscience Institute, Georgia State University, Atlanta, GA 30303, USA.
Nancy G ForgerNeuroscience Institute, Georgia State University, Atlanta, GA 30303, USA.
Matteo PellegriniDepartment of Molecular, Cellular, and Developmental Biology, UCLA, Los Angeles, CA 90095, USA.
Eric VilainDepartment of Human Genetics, David Geffen School of Medicine at University of California Los Angeles (UCLA), Los Angeles, CA 90095, USA.
University of California, Los Angeles · USAllen Institute for Brain Science · USGeorgia State University · USInstitute of Plant and Microbial Biology, Academia Sinica · TW

Funding

Pilot and Feasibility ProgramP30DK041301 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ROZENGURT, JUAN ENRIQUE · 1990 to 2019
$18.0M
Neuroendocrinology, Sex Differences, and ReproductionT32HD007228 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P · 1985 to 2015
$3.9M
NICHD NIH HHS T32 HD007228NIDDK NIH HHS P30 DK041301
6 · The paper itself

Abstract

backgroundThe biological basis for sex differences in brain function and disease susceptibility is poorly understood. Examining the role of gonadal hormones in brain sexual differentiation may provide important information about sex differences in neural health and development. Permanent masculinization of brain structure, function, and disease is induced by testosterone prenatally in males, but the possible mediation of these effects by long-term changes in the epigenome is poorly understood.

methodsWe investigated the organizational effects of testosterone on the DNA methylome and transcriptome in two sexually dimorphic forebrain regions-the bed nucleus of the stria terminalis/preoptic area and the striatum. To study the contribution of testosterone to both the establishment and persistence of sex differences in DNA methylation, we performed genome-wide surveys in male, female, and female mice given testosterone on the day of birth. Methylation was assessed during the perinatal window for testosterone's organizational effects and in adulthood.

resultsThe short-term effect of testosterone exposure was relatively modest. However, in adult animals the number of genes whose methylation was altered had increased by 20-fold. Furthermore, we found that in adulthood, methylation at a substantial number of sexually dimorphic CpG sites was masculinized in response to neonatal testosterone exposure. Consistent with this, testosterone's effect on gene expression in the striatum was more apparent in adulthood.

conclusionTaken together, our data imply that the organizational effects of testosterone on the brain methylome and transcriptome are dramatic and late-emerging. Our findings offer important insights into the long-term molecular effects of early-life hormonal exposure.

Indexed as

Brain sexual differentiationDNA methylationEpigenetic modificationsOrganizational effectsTestosterone

Identifiers

PMID24976947
PMCPMC4074311
OpenAlexW2108429220

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.