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Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice

ABSTRACT: Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice

PROVIDER: PRJNA414476 | ENA |

REPOSITORIES: ENA

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Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice

Project description:Ancestral environmental exposures to non-mutagenic agents can exert effects in unexposed descendants, adding a layer of complexity to long-standing attempts to clarify the relationships between genotypic and phenotypic variations. Transgenerational inheritance of environmental exposures has significant implications for understanding disease etiology. The environmental obesogen hypothesis proposes that exposure to obesogenic chemicals can lead to increased adiposity, in vivo. Here we show that exposure of F0 mice to the obesogen tributyltin (TBT) throughout pregnancy and lactation predisposes unexposed F4 male descendants to obesity when dietary fat is increased. Analyses of body fat, plasma hormone levels, and visceral white adipose tissue DNA methylome and transcriptome collectively indicate that the TBT-dependent F4 obesity is consistent with a leptin resistant, "thrifty phenotype". We found that ancestral TBT exposure induced global changes in DNA methylation together with altered expression of metabolism-relevant genes when the animals were exposed to dietary challenges. Analysis of chromatin accessibility in sperm revealed significant differences between DMSO and TBT groups when guided by DNA sequence composition, a proxy for higher order chromatin organization. Taken together, these data establish an independent connection between ancestral TBT treatment and altered chromatin accessibility that may reflect changes in higher order chromatin organization transmissible through meiosis and mitosis.

2017-11-10 | GSE105051 | GEO

Ancestral perinatal obesogen exposure results in a transgenerational thrifty phenotype in mice.

Project description: Not available

| S-EPMC5722856 | biostudies-literature

Transgenerational Disease Specific Epigenetic Sperm Biomarkers after Ancestral Exposure to Dioxin

Project description:Transgenerational Disease Specific Epigenetic Sperm Biomarkers after Ancestral Exposure to Dioxin

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Primordial Germ Cell Transgenerational Sperm DNA Methylation Epimutations Following Ancestral Vinclozolin Exposure

Project description:Primordial Germ Cell Transgenerational Sperm DNA Methylation Epimutations Following Ancestral Vinclozolin Exposure

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Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral Vinclozolin Exposure

Project description:Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral Vinclozolin Exposure

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Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral DDT Exposure

Project description:Developmental Origins of Transgenerational Sperm DNA Methylation Epimutations Following Ancestral DDT Exposure

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Transgenerational Disease Specific Epigenetic Sperm Biomarkers after Ancestral Exposure to Dioxin

Project description:Dioxin is one of the most common historic industrial contaminants with several major industry and government accidents having exposed large numbers of the worldwide population over the past century. Previous rat studies have demonstrated the ability of dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) exposure to promote the epigenetic transgenerational inheritance of disease susceptibility in subsequent generations. The types of disease observed include testis, ovary, kidney, prostate and obesity pathologies. The current study was designed to use an epigenome-wide association study (EWAS) to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. The transgenerational F3 generation dioxin lineage male rats with and without a specific disease were compared to identify differential DNA methylation regions (DMRs). The genomic features of the DMRs are characterized. Observations demonstrate that disease specific epimutation DMRs exist for the transgenerational dioxin lineage rats that can potentially be used as epigenetic biomarkers for testis, ovary, kidney, prostate and obesity diseases. These disease specific DMRs were associated with genes that have previously been shown to be linked with these diseases. This EWAS for transgenerational disease identified epigenetic biomarkers and provides the proof of concept of the potential to develop similar biomarkers for humans to diagnose disease susceptibilities and facilitate preventative medicine.

2020-12-02 | GSE157539 | GEO

Environmental Toxicant Induced Epigenetic Transgenerational Inheritance of Prostate Pathology and Stromal-Epithelial Cell Epigenome and Transcriptome Alterations: Ancestral Origins of Prostate Disease

Project description:The incidence of prostate disease is increasing, and some of this increase may be attributable to ancestral exposure to environmental toxicants and epigenetic transgenerational inheritance mechanisms. The goal of the current study was to determine the effects that exposure of gestating female rats to vinclozolin has on the epigenetic transgenerational inheritance of prostate disease, and to characterize by what molecular epigenetic mechanisms this has occurred. Results indicate that there were changes in DNA methylation in both cell types.

2018-11-08 | GSE118447 | GEO

Primordial Germ Cell Transgenerational Sperm DNA Methylation Epimutations Following Ancestral Vinclozolin Exposure

Project description:Previously the agricultural fungicide vinclozolin was found to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs) termed epimutations that help mediate this epigenetic inheritance. The current study was designed to investigate the developmental origins of the transgenerational DMRs during gametogenesis. Male control and vinclozolin lineage F3 generation rats were used as a source of embryonic day 13 (E13) primordial germ cells. The DMRs between the control versus vinclozolin lineage samples were determined for this stage.

2020-07-29 | GSE151458 | GEO

Developmental Origins of Transgenerational Sperm Histone Retention Following Ancestral Exposures

Project description:Developmental Origins of Transgenerational Sperm Histone Retention Following Ancestral Exposures

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