Evidence map›Paper›PMID 40806197›Full record

ArticleInternational journal of molecular sciences2025

Chronic Morphine Treatment Leads to a Global DNA Hypomethylation via Active and Passive Demethylation Mechanisms in mESCs.

Manu Araolaza, Iraia Muñoa-Hoyos, Itziar Urizar-Arenaza, Irune Calzado, Nerea Subirán

Abstract read
In one paragraph

Article in International journal of molecular sciences, 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. BenchmarkingInternational journal of molecular sciences · 2026
    Article
  2. How Early-Life Programming During Embryogenesis Imprints Cellular Memory.International journal of molecular sciences · 2025
    Review
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

5 authors.

Manu AraolazaDepartment of Physiology, Faculty of Medicine and Nursery, University of the Basque Country, 48940 Leioa, Spain.ORCID 0000-0003-1838-4594
Iraia Muñoa-HoyosDepartment of Physiology, Faculty of Medicine and Nursery, University of the Basque Country, 48940 Leioa, Spain.ORCID 0000-0002-5107-6991
Itziar Urizar-ArenazaDepartment of Physiology, Faculty of Medicine and Nursery, University of the Basque Country, 48940 Leioa, Spain.ORCID 0000-0002-6390-7887
Irune CalzadoDepartment of Physiology, Faculty of Medicine and Nursery, University of the Basque Country, 48940 Leioa, Spain.ORCID 0000-0002-1787-6792
Nerea SubiránDepartment of Physiology, Faculty of Medicine and Nursery, University of the Basque Country, 48940 Leioa, Spain.ORCID 0000-0001-9202-1287

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Epigenetic regulation, particularly DNA methylation, plays a crucial role in embryonic development by controlling gene expression patterns. The disruption of this regulation by environmental factors can have long-lasting consequences. Opioid drugs, such as morphine, are known to cross the placental barrier and affect the developing central nervous system, yet their precise epigenetic effects during early development remain unclear. This study aimed to elucidate the impact of chronic morphine exposure on the DNA methylation landscape and gene expression in mouse embryonic stem cells (mESCs). mESCs were chronically exposed to morphine (10 μM for 24 h). Genome-wide bisulfite sequencing was performed to identify DNA methylation changes, while RNA sequencing (RNA-Seq) assessed corresponding gene expression alterations. Global levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) were quantified using mass spectrometry. Morphine exposure induced global DNA hypomethylation and identified 16,808 differentially methylated genes (DMGs) related to development, cell signalling, metabolism, and transcriptional regulation. Integrative transcriptomic analysis with RNA-Seq data revealed 651 overlapping genes, including alterations in key epigenetic regulators involved on DNA methylation machinery. Specifically,

Indexed as

DNA DemethylationDNA MethylationMorphineMouse Embryonic Stem Cells5-MethylcytosineAnimalsDNA-Binding ProteinsEpigenesis, GeneticGene Expression ProfilingMicePromoter Regions, GeneticProto-Oncogene Proteins5-hydroxymethylcytosine5-MethylcytosineDNA-Binding ProteinsMorphineProto-Oncogene ProteinsTET1 protein, mousebioinformaticsdevelopmentDNA methylationmESCsmorphinepassive and active demethylation

Identifiers

PMID40806197
PMCPMC12345662

What OpenQuestion holds

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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.