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Epigenome-Wide Association Study for Atrazine Induced Transgenerational Histone Retention Sperm Epigenetic Biomarkers for Disease

ABSTRACT: Epigenome-Wide Association Study for Atrazine Induced Transgenerational Histone Retention Sperm Epigenetic Biomarkers for Disease

PROVIDER: PRJNA658259 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12481604_1.fastq.gz	Fastqsanger.gz
	SRR12481604_2.fastq.gz	Fastqsanger.gz
	SRR12481605_1.fastq.gz	Fastqsanger.gz
	SRR12481605_2.fastq.gz	Fastqsanger.gz
	SRR12481606_1.fastq.gz	Fastqsanger.gz

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Epigenome-Wide Association Study for Atrazine Induced Transgenerational Histone Retention Sperm Epigenetic Biomarkers for Disease

Project description:Atrazine is a common agricultural herbicide previously shown to promote epigenetic transgenerational inheritance of disease to subsequent generations. The current study was designed as an epigenome-wide association study (EWAS) to identify transgenerational sperm disease associated differential histone retention regions (DHRs). Gestating female F0 generation rats were transiently exposed to atrazine during the period of embryonic gonadal sex determination, and then subsequent F1, F2, and F3 generations obtained in the absence of any continued exposure. The transgenerational F3 generation males were assessed for disease and sperm collected for epigenetic analysis. Pathology was observed in late pubertal onset and for testis disease, prostate disease, kidney disease, lean pathology, and multiple disease. For these pathologies, sufficient numbers of individual males with only a single specific disease were identified. The sperm DNA and chromatin were isolated from adult one-year animals with the specific diseases and analyzed for DHRs with histone chromatin immunoprecipitation (ChIP) sequencing. Transgenerational F3 generation males with or without disease were compared to identify the disease specific epimutation biomarkers. No common DHRs were found among all the pathologies. Epimutation gene associations were identified and found to correlate to previously known disease linked genes.

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Atrazine Induced Epigenetic Transgenerational Inheritance of Disease, Lean Phenotype and Sperm Epimutation Pathology Biomarkers

Project description:This study examined the potential transgenerational actions of the herbicide atrazine. The F1 generation offspring (directly exposed as a fetus) derived from the F0 generation exposed gestating female rats did not develop disease, but weighed less compared to controls. The F2 generation (grand-offspring) was found to have increased frequency of testis disease, increased frequency of tumor development in males and females (predominately mammary tumors), early onset puberty in males, and decreased body weight in females compared to controls. The transgenerational F3 generation rats were found to have increased frequency of testis disease, early onset puberty in females, behavioral alterations and a lean phenotype in males and females involving a reduced adipocyte size, decreased body mass index (BMI) and reduced adiposity. The frequency of multiple diseases was significantly higher in the transgenerational F3 generation atrazine lineage males and females. The sperm differential DNA methylation regions (DMRs), termed epimutations, induced by atrazine were identified. A comparison of control versus atrazine lineage sperm identified 519 DMRs (p<10-6) for the F1 generation, 431 DMR (p<10-5) for the F2 generation, and 958 DMR (p<10-9) for the transgenerational F3 generation sperm.

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Developmental Origins of Transgenerational Sperm Histone Retention Following Ancestral Exposures

Project description:This study was designed to investigate the developmental origins of the transgenerational differential histone retention sites (called DHRs) during gametogenesis of the sperm. Vinclozolin and DDT were independently used to promote the epigenetic transgenerational inheritance of these DHRs. Male control, DDT lineage and vinclozolin lineage F3 generation rats were used to isolate round spermatids, caput epididymal spermatozoa, and caudal sperm. The DHRs between the control versus DDT lineage or vinclozolin lineage were determined in these three developmental stages. DHRs and a reproducible core of histone H3 retention sites were observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in the germ cell populations. The chromosomal locations and genomic features of the DHRs were also analyzed. A cascade of epigenetic histone retention site alterations was found to be initiated in or prior to the round spermatids that is further altered during epididymal sperm maturation. Observations show that in addition to alterations in sperm DNA methylation previously identified, the induction of differential histone retention sites (DHRs) in the later stages of spermatogenesis also occurs.

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Glyphosate Induced Transgenerational DNA Methylation and Histone Retention Sperm Epigenetic Biomarkers for Disease

Project description:The herbicide glyphosate has been shown to promote the epigenetic transgenerational inheritance of pathology and disease in subsequent great-grand offspring (F3 generation). This generational toxicology suggests the impacts of environmental exposures need to assess subsequent generations. The current study was designed to identify epigenetic biomarkers for glyphosate induced transgenerational disease. Following a transient glyphosate exposure of a gestating female rat (F0 generation), the subsequent transgenerational F3 generation, with no direct exposure, were aged to 1 year and animals with specific pathologies identified. The pathologies investigated included prostate disease, kidney disease, obesity, and presence of multiple disease. The sperm were collected from the males and used to identify specific differential DNA methylation regions (DMRs) associated with the pathologies. In addition, the differential histone retention sites (DHRs) were examined for the various pathologies as well. Unique signatures of DMRs and DHRs for each pathology were identified for the specific diseases. Interestingly, at a lower statistical threshold overlapping sets of DMRs and DHRs were identified that were common for all the pathologies. The DMR and DHR gene associations were identified and correlated with known pathology associated genes. While the disease biomarker DMR and DHR did not meet typical statistical significance levels, these results may help design future studies with reduced variability. Observations indicate transgenerational epigenetic biomarkers of disease pathology can potentially be identified in the sperm that can assess disease susceptibility. These biomarkers may also suggest epigenetic diagnostics could be used to facilitate preventative medicine.

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Ancestral Plastics Exposure Induces Transgenerational Disease Specific Sperm Epigenome-Wide Association Biomarkers Methylation Epimutation Biomarkers for Specific Transgenerational Disease

Project description:Plastic derived compounds are one of the most frequent daily world-wide exposures. Previously a mixture of plastic derived toxicants involving bisphenol A (BPA), Bis(2-ethylhexyl) phthalate (DEHP), and dibutyl phthalate (DBP) at lower dose exposures of a gestating female rat were found to promote the epigenetic transgenerational inheritance of disease to the offspring (F1 generation), grand-offspring (F2 generation) and great-grand-offspring (F3 generation). Epigenetic analysis of the male sperm was found to result in differential DNA methylation regions (DMRs) in the transgenerational F3 generation male sperm. The current study is distinct and was designed to identify potential sperm DNA methylation biomarkers for specific transgenerational diseases. Observations show disease specific DMRs called epimutations in the transgenerational F3 generation great-grand-offspring rats ancestrally exposed to plastics. The epigenetic DMR biomarkers were identified for testis disease, kidney disease, and multiple (≥2) diseases. These disease sperm epimutation biomarkers were found to be predominantly disease specific. The genomic locations and features of these DMRs were identified. Interestingly, the disease specific DMR associated genes were previously shown to be linked with each of the specific diseases. Therefore, the germline has ancestrally derived epimutations that potentially transmit transgenerational disease susceptibilities. Epigenetic biomarkers for specific diseases could be used as diagnostics to facilitate clinical management of disease and preventative medicine.

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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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Glyphosate Induced Transgenerational DNA Methylation and Histone Retention Sperm Epigenetic Biomarkers for Disease

Project description:Glyphosate Induced Transgenerational DNA Methylation and Histone Retention Sperm Epigenetic Biomarkers for Disease

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Alterations in Sperm DNA Methylation, Non-coding RNA and Histone Retention Associate with DDT Induced Epigenetic Transgenerational Inheritance of Disease

Project description:Environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease through the germline. This study was designed to investigate DDT induced concurrent alterations of a number of different epigenetic processes including DNA methylation and histone retention in sperm. Gestating female rats were exposed transiently to DDT during fetal gonadal development and then F1, F2 and F3 generation sperm were analyzed.

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Project description:Environmental factors have been shown to induce the epigenetic transgenerational inheritance of disease through the germline. This study was designed to investigate vinclozolin induced concurrent alterations of a number of different epigenetic processes including DNA methylation and histone retention in sperm. Gestating female rats were exposed transiently to vinclozolin during fetal gonadal development and then F1, F2 and F3 generation sperm were analyzed.

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