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

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

PROVIDER: PRJNA431998 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR6519430_1.fastq.gz	Fastqsanger.gz
	SRR6519430_2.fastq.gz	Fastqsanger.gz
	SRR6519440_1.fastq.gz	Fastqsanger.gz
	SRR6519440_2.fastq.gz	Fastqsanger.gz
	SRR6519450_1.fastq.gz	Fastqsanger.gz

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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.

2018-04-27 | GSE109775 | GEO

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.

2019-12-31 | GSE137963 | GEO

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

Project description:In previous studies, the pesticide DDT was shown to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs), also called epimutations, which can mediate this epigenetic inheritance. In the current study, the developmental origins of the transgenerational DMRs during gametogenesis have been investigated. Male control and DDT lineage F3 generation rats were used to isolate embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, adult pachytene spermatocytes, round spermatids, caput epididymal spermatozoa, and caudal sperm. The DMRs between the control versus DDT lineage samples were determined at each developmental stage. The top 100 statistically significant DMRs at each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed.

2019-01-19 | GSE121585 | GEO

Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites

Project description:Female and male rats of an outbred female Sprague Dawley rats were administered daily intraperitoneal injections of vinclozolin (100 mg/kg BW/day), or DDT (25 mg/kg BW/day) or dimethyl sulfoxide (DMSO) in oil (1 µl/kg BW/day vehicle). Treatment lineages are designated “control” or “vinclozolin” or “DDT” lineages. The gestating female rats treated were designated as the F0 generation. The offspring of the F0 generation rats were the F1. Non-littermate females and males aged 70-90 days from F1 generation of control, vinclozolin or DDT were bred to obtain F2 generation offspring. The F2 generation rats were similarly bred to obtain the F3 generation offspring. Individuals were maintained for 120 days and euthanized for sperm collection. Sperm from multiple individual rats was pooled into single samples. For the control samples, 2 pools were made using 6 animals and 1 pool with 5 animals. For the DDT samples, 3 pools were mady using 4 animals. For the Vinclozolin samples, 3 pools were made using 4 animals. Genomic DNA was isolated and histone chromatin immunoprecipitation with genomic DNA was performed. Each pooled sample received a separate index primer. NGS was performed at the WSU Spokane Genomics Core using Ilumina HiSeq 2500 with a PE50 application, with a read size of approximately 50 bp and approximately 35 million reads per pool.

2018-01-12 | GSE106125 | GEO

Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites

Project description:Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites

| PRJNA415641 | ENA

Alterations in sperm DNA methylation, non-coding RNA and histone retention associate with DDT-induced epigenetic transgenerational inheritance of disease.

Project description:BACKGROUND:Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. The current study was designed to investigate the DDT-induced concurrent alterations of a number of different epigenetic processes including DNA methylation, non-coding RNA (ncRNA) and histone retention in sperm. METHODS:Gestating females were exposed transiently to DDT during fetal gonadal development, and then, the directly exposed F1 generation, the directly exposed germline F2 generation and the transgenerational F3 generation sperm were investigated. RESULTS:DNA methylation and ncRNA were altered in each generation sperm with the direct exposure F1 and F2 generations being predominantly distinct from the F3 generation epimutations. The piRNA and small tRNA were the most predominant classes of ncRNA altered. A highly conserved set of histone retention sites were found in the control lineage generations which was not significantly altered between generations, but a large number of new histone retention sites were found only in the transgenerational generation DDT lineage sperm. CONCLUSIONS:Therefore, all three different epigenetic processes were concurrently altered as DDT induced the epigenetic transgenerational inheritance of sperm epimutations. The direct exposure generations sperm epigenetic alterations were distinct from the transgenerational sperm epimutations. The genomic features and gene associations with the epimutations were investigated to help elucidate the integration of these different epigenetic processes. Observations demonstrate all three epigenetic processes are involved in transgenerational inheritance. The different epigenetic processes appear to be integrated in mediating the epigenetic transgenerational inheritance phenomenon.

| S-EPMC5827984 | biostudies-literature

Sperm Epimutation Biomarkers of Obesity and Pathologies following DDT Induced Epigenetic Transgenerational Inheritance of Disease

Project description:Gestating F0 generational female rats were transiently exposed to DDT during fetal gonadal sex determination and the incidence of adult onset pathologies was assessed in the subsequent F1, F2, and F3 generations. In addition, sperm differential DNA methylation regions (DMRs) that were associated with specific pathologies in the F3 generation males were investigated. No pathology was observed in the F1 generation DDT lineage males or females compared with F1 generation controls (vehicle exposure). There was an increase of testis disease and early onset puberty in the F2 generation DDT lineage males. The F3 generation DDT males had significant increases in testis disease, prostate disease, and late onset puberty. The F3 generation DDT females had significant increases in ovarian and kidney disease. Both the F3 generation males and females had significant increases in the frequency of obesity and multiple disease. The F3 generation sperm was collected to examine DMRs for the ancestrally exposed DDT male population. Unique sets of DMRs were associated with late onset puberty, kidney disease, and multiple disease pathologies.

2018-07-31 | GSE114032 | GEO

Epigenetic Transgenerational Inheritance of Altered Sperm Histone Retention Sites.

Project description:A variety of environmental toxicants and factors have been shown to induce the epigenetic transgenerational inheritance of disease and phenotypic variation. Epigenetic alterations in the germline (sperm or egg) are required to transmit transgenerational phenotypes. The current study was designed to investigate the potential role of histones in sperm to help mediate the epigenetic transgenerational inheritance. The agricultural fungicide vinclozolin and the pesticide DDT (dichlorodiphenyltrichloroethane) were independently used to promote the epigenetic transgenerational inheritance of disease. Purified cauda epididymal sperm were collected from the transgenerational F3 generation control and exposure lineage male rats for histone analysis. A reproducible core of histone H3 retention sites was observed using an H3 chromatin immunoprecipitation (ChIP-Seq) analysis in control lineage sperm. Interestingly, the same core group of H3 retention sites plus additional differential histone retention sites (DHRs) were observed in the F3 generation exposure lineage sperm. Although new histone H3 retention sites were observed, negligible change in histone modification (methylation of H3K27me3) was observed between the control and exposure lineages. Observations demonstrate that in addition to alterations in sperm DNA methylation and ncRNA previously identified, the induction of differential histone retention sites (DHRs) also appear to be involved in environmentally induced epigenetic transgenerational inheritance.

| S-EPMC5871750 | biostudies-literature

Sperm Epimutation Biomarkers of Obesity and Pathologies following DDT Induced Epigenetic Transgenerational Inheritance of Disease

Project description:Sperm Epimutation Biomarkers of Obesity and Pathologies following DDT Induced Epigenetic Transgenerational Inheritance of Disease

| PRJNA459562 | ENA

Alterations in sperm DNA Methylation, Non-Coding RNA expression, and histone retention mediate Vinclozolin 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 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.

2018-06-05 | GSE111441 | GEO

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