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Multiple Generation Distinct Toxicant Exposures Induce Epigenetic-Transgenerational-Inheritance of Enhanced Pathology and Obesity

ABSTRACT: Multiple Generation Distinct Toxicant Exposures Induce Epigenetic-Transgenerational-Inheritance of Enhanced Pathology and Obesity

PROVIDER: PRJNA1023875 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26277356_1.fastq.gz	Fastqsanger.gz
	SRR26277356_2.fastq.gz	Fastqsanger.gz
	SRR26277364_1.fastq.gz	Fastqsanger.gz
	SRR26277364_2.fastq.gz	Fastqsanger.gz
	SRR26277365_1.fastq.gz	Fastqsanger.gz

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Multiple Generation Distinct Toxicant Exposures Induce Epigenetic-Transgenerational-Inheritance of Enhanced Pathology and Obesity

Project description:This study examines the actions of the agricultural fungicide vinclozolin on the F0 generation, followed by jet fuel hydrocarbon mixture exposure of the F1 generation, and then pesticide DDT (dichlorodiphenyltrichloroethane) on the F2 generation gestating females. The subsequent F3 and F4 generations and F5 transgenerational-generation were examined for male sperm epigenetic alterations and pathology in males and females. Significant impacts on the male sperm differential DNA methylation regions (DMRs) were observed. The F3-F5 generations were similar in approximately 50% of the DMRs. The pathology of each generation was assessed in the testis, ovary, kidney, prostate, obesity, and tumors. The pathology used a newly developed Deep Learning (DL), artificial intelligence (AI), based histopathology analysis. Observations demonstrated compounded disease impacts in obesity and metabolic parameters, but other pathologies plateaued with smaller increases at the F5 transgenerational generation. Therefore, the multiple generational exposures, which occurs in human populations, may increase epigenetic impacts and disease susceptibility.

2024-12-02 | GSE244603 | GEO

Epigenetic Transgenerational Inheritance of Parent-of-Origin Allelic Transmission of Outcross Pathology and Sperm Epimutations Following Ancestral Toxicant Exposures

Project description:Epigenetic Transgenerational Inheritance of Parent-of-Origin Allelic Transmission of Outcross Pathology and Sperm Epimutations Following Ancestral Toxicant Exposures

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Epigenetic Transgenerational Inheritance of Parent-of-Origin Allelic Transmission of Outcross Pathology and Sperm Epimutations Following Ancestral Toxicant Exposures

Project description:Previous observations have demonstrated that the agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) induce transgenerational sperm epimutations involving DNA methylation. These two environmental toxicants were used to investigate the impacts of parent-of-origin outcross on the epigenetic transgenerational inheritance of disease. Male and female rats were collected from a paternal outcross (POC) or a maternal outcross (MOC) F4 generation control and exposure lineages for pathology and epigenetic analysis. This model allows the parental allelic transmission of disease and epimutations to be investigated. There was increased pathology incidence in MOC outcross F4 generation male prostate, kidney, obesity and multiple diseases through a maternal allelic transmission. The POC outcross F4 generation female offspring had increase pathology incidence for kidney, obesity and multiple diseases through the paternal allelic transmission. Some disease such as testis or ovarian pathology appear to be transmitted through the combined actions of both male and female alleles. Analysis of the F4 generation sperm epigenomes identified differential DNA methylated regions (DMRs) in a genome-wide analysis. Observations demonstrate that DDT and vinclozolin have the potential to promote the epigenetic transgenerational inheritance of disease and sperm epimutations to the outcross F4 generation in a sex specific and exposure specific manner.

2019-07-23 | GSE130258 | GEO

Epigenetic Transgenerational Inheritance of Testis Pathology and Sertoli Cell Epimutations: Generational Origins of Male Infertility

Project description:Environmental toxicant induced epigenetic transgenerational inheritance has been shown to affect testis pathology and sperm count. Sertoli cells have an essential role in spermatogenesis by providing physical and nutritional support for developing germ cells. The current study was designed to further investigate the transgenerational epigenetic changes in the rat Sertoli cell epigenome that are associated with the onset of testis disease.

2018-11-08 | GSE118306 | GEO

Examination of Generational Impacts of Adolescent Chemotherapy: Ifosfamide and Potential for Epigenetic Transgenerational Inheritance

Project description:The current study was designed to use a rodent model to determine if exposure to the chemotherapy drug ifosfamide during puberty can induce altered phenotypes and disease in the grand-offspring of exposed individuals through epigenetic transgenerational inheritance. Numerous toxicant exposures during critical developmental windows can have generational impacts through this non-genetic inheritance mechanism. Pathologies such as delayed pubertal onset, kidney disease and multiple pathologies were observed to be significantly more frequent in the F1 generation offspring of ifosfamide lineage females. The F2 generation grand-offspring ifosfamide lineage males had transgenerational pathology phenotypes of early pubertal onset and reduced testis pathology. Reduced levels of anxiety were observed in both males and females from the exposure lineage in the transgenerational F2 generation grand-offspring. Differential DNA methylated regions (DMRs) were also identified in chemotherapy and control lineages sperm in the F1 and F2 generations. The transgenerational alterations in sperm epigenetics provides a molecular mechanism for the ancestral impacts of chemotherapy. Therefore, chemotherapy exposure can impact pathology and disease susceptibility in subsequent generations.

2022-11-30 | GSE217141 | GEO

Environmental Induced Epigenetic Transgenerational Inheritance of Pathology: Systems Epigenetics in Disease Etiology and Generational Toxicology

Project description:Several epigenome-wide association studies (EWAS) have been shown to identify epigenetic alterations (i.e., epimutations) associated with diseases. The sperm epimutations potentially involved in the transgenerational inheritance of specific pathologies have been identified. Transgenerational sperm epimutations associated with kidney, prostate, puberty, testis, obesity, and multiple pathologies have been identified for a variety of environmental toxicants including dioxin, plastics, pesticides, glyphosate, methoxychlor, atrazine, and jet fuel. The transgenerational sperm epimutations for exposure and disease-specific epimutations have been identified in these EWAS studies. The current study used the information from these previous toxicant-induced epigenetic transgenerational inheritance EWAS rat studies and adds a comparable control group, rats that have not been exposed to any particular toxicant. Two additional control groups were collected and are presented here.

2022-04-27 | GSE198452 | GEO

Multiple generation distinct toxicant exposures induce epigenetic transgenerational inheritance of enhanced pathology and obesity.

Project description:Three successive multiple generations of rats were exposed to different toxicants and then bred to the transgenerational F5 generation to assess the impacts of multiple generation different exposures. The current study examines the actions of the agricultural fungicide vinclozolin on the F0 generation, followed by jet fuel hydrocarbon mixture exposure of the F1 generation, and then pesticide dichlorodiphenyltrichloroethane on the F2 generation gestating females. The subsequent F3 and F4 generations and F5 transgenerational generation were obtained and F1-F5 generations examined for male sperm epigenetic alterations and pathology in males and females. Significant impacts on the male sperm differential DNA methylation regions were observed. The F3-F5 generations were similar in ∼50% of the DNA methylation regions. The pathology of each generation was assessed in the testis, ovary, kidney, and prostate, as well as the presence of obesity and tumors. The pathology used a newly developed Deep Learning, artificial intelligence-based histopathology analysis. Observations demonstrated compounded disease impacts in obesity and metabolic parameters, but other pathologies plateaued with smaller increases at the F5 transgenerational generation. Observations demonstrate that multiple generational exposures, which occur in human populations, appear to increase epigenetic impacts and disease susceptibility.

| S-EPMC10756336 | biostudies-literature

Environmental Toxicant Induced Epigenetic Transgenerational Inheritance of Ovarian Pathology and Granulosa Cell Epigenome and Transcriptome Alterations: Ancestral Origins of PCO and POI

Project description:Previous studies have shown that exposure to a number of environmental toxicants can promote the epigenetic transgenerational inheritance of ovarian disease, including decreases in the primordial follicle pool of oocytes that are similar to what is seen in POI, and increases in ovarian cysts that are similar to what is seen in PCOS. In the current study, transgenerational changes to the epigenome of ovarian granulosa cells are characterized in F3 generation rats after ancestral vinclozolin or DDT exposures compared to controls. In purified granulosa cells from 20 day old F3 generation females 164 differentially methylated regions (DMRs) (p<1e-06) were found in the F3 generation vinclozolin lineage, and 293 DMRs (p<1e-06) in the DDT lineage, compared to controls.

2018-11-08 | GSE118381 | 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

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

| PRJNA485687 | ENA

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