MiRNA profile of young mice and aged mice
Ontology highlight
ABSTRACT:
ORGANISM(S): synthetic construct Mus musculus
PROVIDER: GSE232620 | GEO | 2023/12/07
REPOSITORIES: GEO
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Project description:Autism spectrum disorder (ASD) has increased over ten-fold over the past several decades, and appears predominantly associated with paternal transmission. Although genetics is anticipated to be a component of ASD etiology, environmental epigenetics is now thought to be an important factor. Epigenetic alterations, such as DNA methylation have been correlated with ASD. The current study was designed to identify a DNA methylation signature in sperm as a potential biomarker to identify paternal offspring autism susceptibility. Sperm samples were obtained from fathers, many undergoing in vitro fertilization (IVF) procedures, that have children with or without autism, and the sperm then assessed for alterations in DNA methylation. Differential DNA methylation regions (DMRs) were identified in the sperm of fathers with autistic children in comparison to those without ASD children. An MeDIP-seq procedure was used to identify DMRs. The genomic features and genes associated with the DMRs were identified. The potential sperm DMR biomarker was validated with a blinded test set of individuals. Observations demonstrate a significant set of DMRs in sperm can potentially act as a biomarker for paternal offspring autism susceptibility.
2020-12-01 | GSE157417 | GEO
Project description:Background: Epidemiological studies have reported an association between advanced paternal age at conception and an increased risk of neurodevelopmental disorders in offspring, such as autism spectrum disorder. Evidence suggests that DNA methylation alterations in sperm of older men may be transmitted to the feto-placental unit and associated with offspring brain development and behavioral differences later in childhood. Objective: We aimed to assess the association of advanced paternal age with DNA methylation alterations in the human placenta and compare the results to previous findings in sperm. Methods: For this study, 64 placenta samples from the 3D (Design, Develop, Discover) prospective birth cohort study were categorized based on paternal age at conception. DNA methylation of the placenta was interrogated using the Illumina 850K array. There were no differentially methylated sites found to be statistically significant after correction for multiple comparisons, therefore sites with significant nominal p-values <0.05 were assessed and used to define differentially methylated regions (DMRs) associated with genes. Results: Advanced paternal age was associated with DNA methylation alterations in the placenta at up to 688 genes, with a predominance of hypomethylation (65%), including at 8 imprinted loci. About 7% of genes with age-associated DNA methylation changes in placenta overlapped with genes previously reported to show altered DNA methylation in sperm of older men; seven genes common to placenta and sperm had previously been identified in association with susceptibility to autism spectrum disorder. Amongst loci most affected, we found evidence of sex-specific hypermethylation at genes linked to neurodevelopment (GRM7, EBF3, FOXG1). Conclusion: Our findings suggest that advanced paternal age at conception is associated with altered DNA methylation in the human placenta, including at genes tied to neurodevelopment. This study highlights the use of the placenta DNA methylome as a surrogate marker for the potential impact of advanced paternal age on the child.
2025-12-11 | GSE273723 | GEO
Project description:Sperm DNA Methylation Epimutation Biomarker for Paternal Offspring Autism Susceptibility
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Project description:Pyrethroid insecticides are widely used in agriculture and households, and their exposure can affect neurodevelopment. Few studies have evaluated how preconception parental exposure could also affect this process. To address knowledge gap, adult C57Bl6/J mice were gavaged daily with -cypermethrin at a human relevant low (0.3 mg/kg) or high (10 mg/kg) dose in corn oil for four weeks prior to conception. Offspring embryonic day 16 dorsal forebrain was extracted for transcriptomic analysis. In offspring forebrains of exposed compared to unexposed parents, there was increasing number of differentially expressed genes (DEGs) from paternal (least) to maternal to both parent exposure (most). A dose dependent effect was observed in offspring forebrain for paternal and maternal preconceptual exposures. Maternal and both parent exposures led to upregulated genes in offspring brain for biological processes involved in translation with predicted activation of EIF4E, a gene associated with autism. In contrast, paternal exposure upregulated cell cycle related DNA damage signaling processes. After any parent exposure, there was upregulation of biological processes involved in mitochondria function and oxidative stress and a downregulation of neuronal and synaptic processes with predicted inhibition of BDNF signaling. Weighted gene correlation network analysis identified modules associated with different parent treatment that were over-represented with DEGs with similar functional signatures as found in DEG-related pathways. Importantly, DEGs in offspring forebrain after any parent exposure were over-represented with genes related to autism spectrum disorder (ASD) and stress vulnerability. The study highlights the potential contribution of preconception parental pyrethroid exposure to aberrant brain functioning.
2025-08-22 | GSE300410 | GEO
Project description:The global prevalence of type 2 diabetes (T2D) is increasing, and it is contributing to the susceptibility to diabetes and its related epidemic in offspring. Although the impacts of paternal T2D on metabolism of offspring have been well established, the exact molecular and mechanistic basis that mediates these impacts remains largely unclear. Here we show that paternal T2D increases the susceptibility to diabetes in offspring through the gametic epigenetic alterations. Paternal T2D led to glucose intolerance and insulin resistance in offspring. Relative to controls, offspring of T2D fathers exhibited altered gene expression patterns in the pancreatic islets, with downregulation of several genes involved in glucose metabolism and insulin signaling pathway. Epigenomic profiling of offspring pancreatic islets revealed numerous changes in cytosine methylation depending on paternal T2D, including reproducible changes in methylation over several insulin signaling genes. Paternal T2D altered overall methylome patterns in sperm, with a large portion of differentially methylated genes overlapped with that of pancreatic islets in offspring. Our study revealed, for the first time, that T2D can be inherited transgenerationally through the mammalian germline by an epigenetic manner. Examination of the effect of paternal T2D on the DNA methylation in the pancreatic islets of offspring and in the sperm of father.
2013-01-02 | E-GEOD-43238 | biostudies-arrayexpress
Project description: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. 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. 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.
2026-05-19 | GSE306033 | GEO
Project description: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. 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. 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.
2026-05-19 | GSE306034 | GEO
Project description: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. 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. 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.
2026-05-19 | GSE306044 | GEO
Project description:Spermatogonial stem cells (SSC), the foundation of spermatogenesis and male fertility, possess lifelong self-renewal activity. Aging leads to the decline in stem cell function and increased risk of paternal age-related genetic diseases. Epigenetic profiling revealed reduced H3K27me3 deposition at numerous pro-differentiation genes during SSC differentiation as well as aberrant H3K27me3 distribution at genes in Wnt and TGF-β signaling upon aging.
2021-06-14 | GSE164603 | GEO
Project description:Spermatogonial stem cells (SSC), the foundation of spermatogenesis and male fertility, possess lifelong self-renewal activity. Aging leads to the decline in stem cell function and increased risk of paternal age-related genetic diseases. Aged SSCs exhibited gene body hypomethylation, which is accompanied by an elevated 5hmC level.
2021-06-14 | GSE164606 | GEO