Evidence map›Paper›PMID 40785069›Full record

ArticleEpigenetics2025

Sex-stratified piRNA expression analysis reveals shared functional impacts of perinatal lead (Pb) exposure in murine hearts.

Kimberley E Sala-Hamrick, Kai Wang, Bambarendage P U Perera, Maureen A Sartor, Laurie K Svoboda, Dana C Dolinoy

Abstract read
In one paragraph

Article in Epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

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

2 citing papers in PubMed.

  1. Review
  2. Article
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

6 authors.

Kimberley E Sala-HamrickDepartment of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-8870-5296
Kai WangDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0002-8541-7563
Bambarendage P U PereraDepartment of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-7774-0985
Maureen A SartorDepartment of Computational Medicine and Bioinformatics, University of Michigan Medical School, Ann Arbor, MI, USA.ORCID 0000-0001-6155-5702
Laurie K SvobodaDepartment of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-0003-4513
Dana C DolinoyDepartment of Environmental Health Sciences, School of Public Health, University of Michigan, Ann Arbor, MI, USA.ORCID 0000-0002-3304-2456

Funding

Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AMY J SCHULZ · 2011 to 2026
$21.3M
TSPO and Neuroinflammation in Alzheimer's DiseaseR01ES007062 · NIEHS · JOHNS HOPKINS UNIVERSITY · PI GUILARTE, TOMAS R · 1995 to 2023
$7.3M
Environmental Epigenomics and Precision Environmental HealthR35ES031686 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Dana Dolinoy · 2020 to 2026
$6.1M
Sex-Specific Metabolic and Epigenetic Programming of Cardiac Differentiation by Developmental Lead Exposure.K01ES032048 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SVOBODA, LAURIE KATHLEEN · 2020 to 2022
$468k
NIEHS NIH HHS K01 ES032048NIEHS NIH HHS P30 ES017885NIEHS NIH HHS R01 ES007062NIEHS NIH HHS R35 ES031686
6 · The paper itself

Abstract

The landscape of PIWI-interacting RNA (piRNA) expression in the heart is poorly understood, particularly regarding sex differences. Altered piRNA expression has been reported in cardiovascular disease (CVD), and although exposure to the metal lead (Pb) is strongly associated with CVD risk, no studies have investigated Pb's effects on cardiac piRNAs. This study aimed to characterize piRNA expression in the murine heart and assess sex-specific effects of human-relevant maternal Pb exposure on adult offspring cardiac piRNA expression. piRNAs were identified from whole mouse hearts using sodium periodate exclusion of small RNA and subsequent sequencing. Control mice expressed 18,956 piRNAs in combined-sex analysis; sex-specific analyses revealed 9,231 piRNAs in female hearts and 5,972 piRNAs in male hearts. Genomic mapping showed 28-41% aligned to introns, while 12-28% mapped to exons. Comparing control and Pb-exposed hearts, we found more potential Pb-induced expression changes in females (847) compared to males (187) (p-value < 0.05 and |logFC| > 1). These piRNAs were significantly enriched near genes involved in biological processes related to heart function and CVD development, including mitochondrial function, energy metabolism, and cardiac muscle structure (FDR < 0.05). Overall, we characterized combined and sex-stratified piRNA expression in both control and Pb-exposed murine hearts. In addition to providing a foundation for sex-specific piRNA expression in the heart, these findings suggest a novel epigenetic mechanism by which developmental Pb exposure may impact CVD risk later in life. Future studies will link these sex-specific molecular changes to Pb-induced alterations in cardiac function.

Indexed as

HeartLeadMyocardiumPrenatal Exposure Delayed EffectsRNA, Small InterferingAnimalsFemaleHumansMaleMicePiwi-Interacting RNAPregnancySex FactorsLeadPiwi-Interacting RNARNA, Small Interferingcardiacdevelopmental origins of health and disease (DOHaD)environmental epigenomicsheartPbpiRNAsex differencestoxicoepigenetics

Identifiers

PMID40785069
PMCPMC12341058

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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.