Evidence mapPaperPMID 40040952Full record

ArticleEnvironmental epigenetics2025

Transgenerational inheritance of hepatic steatosis in mice: sperm methylome is largely reprogrammed and inherited but does not globally influence liver transcriptome.

Sílvia Ribó, Marta Ramon-Krauel, Josep M Marimon-Escude, Florence Busato, Flavio Palmieri, Marta Mourin-Fernandez, Ivonne Palacios-Marin, Ruben Diaz, Carles Lerin, Rafael Oliva and 2 more

Abstract read
In one paragraph

Article in Environmental epigenetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Sílvia RibóInstitut de Recerca Sant Joan de Déu (IRSJD), Endocrinology, Esplugues 08950, Spain.
Marta Ramon-KrauelInstitut de Recerca Sant Joan de Déu (IRSJD), Endocrinology, Esplugues 08950, Spain.ORCID https://orcid.org/0000-0003-3027-9105
Josep M Marimon-EscudeUniversitat de Barcelona-Centres Científics i Tecnològics, Barcelona 08028, Spain.ORCID https://orcid.org/0009-0006-3013-1257
Florence BusatoLaboratory for Epigenetics and Environment, Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie François Jacob, Université Paris-Saclay, Evry 91000, France.
Flavio PalmieriUniversitat de Barcelona-Facultat Medicina-Bellvitge, L'Hospitalet 08907, Spain.
Marta Mourin-FernandezInstitut de Recerca Sant Joan de Déu (IRSJD), Endocrinology, Esplugues 08950, Spain.
Ivonne Palacios-MarinInstitut de Recerca Sant Joan de Déu (IRSJD), Endocrinology, Esplugues 08950, Spain.
Ruben DiazInstitut de Recerca Sant Joan de Déu (IRSJD), Endocrinology, Esplugues 08950, Spain.
Carles LerinInstitut de Recerca Sant Joan de Déu (IRSJD), Endocrinology, Esplugues 08950, Spain.
Rafael OlivaMolecular Biology of Reproduction and Development, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, and Hospital Clinic Barcelona 08036, Spain.ORCID https://orcid.org/0000-0003-4876-2410
Jorg TostLaboratory for Epigenetics and Environment, Centre National de Recherche en Génomique Humaine, CEA-Institut de Biologie François Jacob, Université Paris-Saclay, Evry 91000, France.ORCID https://orcid.org/0000-0002-2683-0817
Josep C Jiménez-ChillarónInstitut de Recerca Sant Joan de Déu (IRSJD), Endocrinology, Esplugues 08950, Spain.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Nutritional challenges and obesity can contribute to the transmission of metabolic diseases through epigenetic mechanisms. Among them, DNA methylation stands out as a potential carrier of information because germline cytosine methylation responds to environmental factors and can be transmitted across generations. Yet, it remains unclear whether inherited DNA methylation plays an active role in the inheritance of metabolic phenotypes or solely influences expression of a few genes that cannot recapitulate the whole metabolic spectrum in the next generation offspring. Previously, we established a mouse model of childhood obesity by reducing litter size at birth. Mice raised in small litters (SL) developed obesity, insulin resistance, and hepatic steatosis. The offspring (SL-F1) and grand-offspring (SL-F2) of SL males also exhibited hepatic steatosis. Here, we aimed to investigate whether germline DNA methylation could serve as a carrier of phenotypic information, hepatic steatosis, between generations. Litter size reduction significantly altered global DNA methylation profile in the sperm of SL-F0 males. Remarkably, 8% of these methylation marks remained altered in the sperm of SL-F1 mice and in the liver of SL-F2 mice. These data suggest that germline DNA methylation is sensitive to environmental challenges and holds significant heritability, either through direct germline transmission and/or through sequential erasure and reestablishment of the marks in the following generations. Yet, DNA methylation did not strongly correlate with the hepatic transcriptome in SL-F2 mice, suggesting that it does not directly drive phenotypes in the F2. As an alternative, germline DNA methylation could potentially influence the phenotype of the next generation by modulating the expression of a reduced number of key transcription factors that, through an amplification cascade, drive phenotypic outcomes in subsequent generations.

Indexed as

childhood obesityDNA methylationhepatic steatosismouse modelspermtransgenerational epigenetic inheritance

Identifiers

PMID40040952
PMCPMC11879089

What Socratic holds

Textmetadata
LicenceCC BY-NC
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.