Evidence mapPaperPMID 39894169Full record

ArticleToxicology and applied pharmacology2025

Heritable dysregulation of DNA methylation may underlie the diabetogenic effects of paternal preconception exposure to inorganic arsenic in C57BL/6J mice.

Hadley J Hartwell, Bingzhen Shang, Christelle Douillet, Audrey G Bousquet, Tianyi Liu, Fei Zou, Folami Ideraabdullah, Miroslav Stýblo, Rebecca C Fry

Abstract read
In one paragraph

Article in Toxicology and applied pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
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

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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

3 citing papers in PubMed.

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4 · The record

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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

9 authors.

Hadley J HartwellDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bingzhen ShangDepartment of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Christelle DouilletDepartment of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Audrey G BousquetDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Tianyi LiuDepartment of Biostatistics, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Fei ZouDepartment of Biostatistics, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Folami IderaabdullahDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Genetics, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Miroslav StýbloDepartment of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: styblo@med.unc.edu.
Rebecca C FryDepartment of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: rfry@email.unc.edu.

Funding

The UNC Chapel Hill Superfund Research Program (UNC-SRP)P42ES031007 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · 2022 to 2025
$9.3M
UNIV OF NORTH CAROLINA CLINICAL NUTRITION RESEARCH UNITP30DK056350 · UNIV OF NORTH CAROLINA CHAPEL HILL · 1999 to 2025
$5.9M
Genetic underpinning of diabetes associated with arsenic exposureR01ES029925 · NIEHS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Rebecca Fry, Fernando Pardo-Manuel de Villena · 2022 to 2023
$1.3M
Humanized mouse models for arsenic toxicologyR01ES032643 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2025 to 2025
$396k
NIDDK NIH HHS P30 DK056350NIEHS NIH HHS P42 ES031007NIEHS NIH HHS R01 ES028721NIEHS NIH HHS R01 ES029925NIEHS NIH HHS R01 ES032643
6 · The paper itself

Abstract

Chronic exposure to inorganic arsenic (iAs) has been linked with the development of diabetes mellitus (DM). We recently showed that parental exposure to iAs (200 ppb) prior to mating was associated with diabetic phenotypes in offspring and altered gene expression in parents and offspring. The goal of the present study was to determine if DNA methylation underlies the differential gene expression in the livers of offspring. DNA methylation was assessed in paternal (G0) sperm and livers of their offspring (G1) using a genome wide DNA methylation array. We found that iAs exposure significantly altered CpG methylation (p < 0.05) in 54.3 %, 49.4 %, and 63.7 % of the differentially expressed genes in G0 sperm, G1 female livers, and G1 male livers, respectively. Importantly, a subset of differentially methylated CpG sites were shared across generations. Sensitivity analyses (FDR < 0.1) of imprinted and DM-associated genes revealed differential methylation of 74 imprinted genes and 100 DM-associated genes in the livers of G1 males. These male-specific results are intriguing given the prior findings of diabetic phenotypes found exclusively in male offspring from parents exposed to iAs. In summary, these data demonstrate that heritable changes in DNA methylation through the paternal germline may underlie the diabetogenic effects of preconception iAs exposure.

Indexed as

ArsenicDiabetes MellitusDNA MethylationPaternal ExposureAnimalsCpG IslandsFemaleGenomic ImprintingLiverMaleMiceMice, Inbred C57BLPregnancyPrenatal Exposure Delayed EffectsSpermatozoaArsenicArsenicDiabetesDNA methylationEpigeneticsHeritablePrenatal exposure

Identifiers

PMID39894169
PMCPMC11846692

What Socratic holds

Textmetadata
LicenceTDM
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 Socratic graph.