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Excel · study · 2026

Paternal early-life stress and diet influence female offspring behavior through sperm DNA methylation and transcriptomic alterations in the Amygdala [Sperm_methylation_F0]

Listed in NCBI GEO

Obesity is a global epidemic influenced by stress-related experiences during development, which can program behavioral traits, with the amygdala playing a central role in stress regulation.

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These programmed effects may be inherited through epigenetic mechanisms. Here, we examined the impact of paternal early-life stress (ELS), alone or combined with a high-fat diet (HFD), on offspring behavior and gene regulation.

Male Wistar rats underwent maternal separation to induce ELS, followed by elevated plus maze (EPM) testing and exposure to either HFD or standard chow. These males were bred with naïve females, and F1 offspring were raised under standard conditions. Amygdala tissue and sperm were collected; RNA from paternal and offspring amygdalae was deep-sequenced, and sperm DNA was analyzed using Reduced Representation Bisulfite Deep Sequencing (RRBS.

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Paternal exposure to ELS and HFD independently and jointly altered physiology and behavior in F1 female offspring. Offspring of ELS fathers showed increased exploratory behavior and mobility in the EPM, while; paternal HFD increased time spent in open arms. In the paternal amygdala, ELS and HFD induced distinct gene expression changes.

Sperm methylation analysis revealed hundreds of differentially methylated genes, many overlapping with transcriptional changes in the F1 female amygdala, supporting a role for epigenetic inheritance. Overlapping expression patterns in F0 and F1 included genes involved in dopamine signaling and epigenetic regulation. Notably, the imprinted gene GRB10 showed increased promoter methylation in sperm and reduced expression in both paternal and offspring amygdala, validated by immunostaining.

These findings suggest that paternal ELS and HFD shape offspring phenotype through heritable epigenetic modifications.

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From keywords
Life Sciences
Inferred from text
Sequencing 75%
Provenance · 1 source records, 8 field assertions
SourceKeyLast seenRaw
NCBI GEOGSE30604412 d agoJSON v1
FieldAssertionExtractorEvidence
access_levelsource · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[field].local:field:life-sciencesmapping · NCBI GEOconnector:ncbi_geo@1.0.0
concepts[method].geo_series_type:methylation-profiling-by-high-throughput-sequencingsource · NCBI GEOconnector:ncbi_geo@1.0.0/gdstype
concepts[modality].local:modality:sequencingenrichment · NCBI GEOkeyword-concept-rules@1.0.0title+description (75%)
concepts[organism].NCBITaxon:10116source · NCBI GEOconnector:ncbi_geo@1.0.0/taxon
descriptionsource · NCBI GEOconnector:ncbi_geo@1.0.0/summary
publication_datesource · NCBI GEOconnector:ncbi_geo@1.0.0
titlesource · NCBI GEOconnector:ncbi_geo@1.0.0/title