Vinclozolin induced epigenetic transgenerational inheritance of pathologies and sperm epimutation biomarkers for specific diseases
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE113785 | GEO | 2018/07/25
REPOSITORIES: GEO
Similar Datasets
Project description:Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination appears to promote an epigenetic reprogramming of the male germ line that is associated with transgenerational adult-onset disease states. Transgenerational effects on the embryonic day 16 (E16) testis demonstrated reproducible changes in the testis transcriptome for multiple generations (F1-F3). The expression of 196 genes was found to be influenced, with the majority of gene expression being decreased or silenced. Dramatic changes in the gene expression of methyltransferases during gonadal sex determination were observed in the F1 and F2 vinclozolin generation (E16) embryonic testis, but the majority returned to control-generation levels by the F3 generation. The most dramatic effects were on the germ-line-associated Dnmt3A and Dnmt3L isoforms. Observations demonstrate that an embryonic exposure to vinclozolin appears to promote an epigenetic reprogramming of the male germ line that correlates with transgenerational alterations in the testis transcriptome in subsequent generations. Experiment Overall Design: E16 Testis RNA samples from F1, F2, F3 generation control groups are compared to F1, F2, F3 generation vinclozolin treated groups
2008-04-04 | E-GEOD-10919 | biostudies-arrayexpress
Project description:The ability of an endocrine disruptor exposure during gonadal sex determination to promote a transgenerational prostate disease phenotype was investigated in the current study. METHODS: Exposure of an F0 gestating female rat to the endocrine disruptor vinclozolin during F1 embryo gonadal sex determination promoted a transgenerational adult onset prostate disease phenotype. The prostate disease phenotype and physiological parameters were determined for males from F1 to F4 generations and the prostate transcriptome was assessed in the F3 generation. RESULTS: Although the prostate in prepubertal animals develops normally, abnormalities involving epithelial cell atrophy, glandular dysgenesis, prostatitis, and hyperplasia of the ventral prostate develop in older animals. The ventral prostate phenotype was transmitted for four generations (F1-F4). Analysis of the ventral prostate transcriptome demonstrated 954 genes had significantly altered expression between control and vinclozolin F3 generation animals. Analysis of isolated ventral prostate epithelial cells identified 259 genes with significantly altered expression between control and vinclozolin F3 generation animals. Characterization of regulated genes demonstrated several cellular pathways were influenced, including calcium and WNT. A number of genes identified have been shown to be associated with prostate disease and cancer, including beta-microseminoprotein (Msp) and tumor necrosis factor receptor superfamily 6 (Fadd). CONCLUSIONS: The ability of an endocrine disruptor to promote transgenerational prostate abnormalities appears to involve an epigenetic transgenerational alteration in the prostate transcriptome and male germ-line. Potential epigenetic transgenerational alteration of prostate gene expression by environmental compounds may be important to consider in the etiology of adult onset prostate disease. Keywords: expression analysis, transgenerational changes due to Vinclozolin
2008-06-20 | GSE11842 | GEO
Project description:Permethrin and N,N-diethyl-meta-toluamide (DEET) are the pesticides and insect repellent most commonly used by humans. These pesticides have been shown to promote the epigenetic transgenerational inheritance of disease in rats. The current study was designed as an epigenome-wide association study (EWAS) to identify potential sperm differential DNA methylation regions (DMRs) for specific transgenerational disease. Outbred Sprague Dawley gestating female rats (F0) were exposed to the pesticide combination including Permethrin and DEET. Their great-grand offspring (F3) were only transgenerationally exposed to pesticides. The transgenerational adult male rat sperm were collected from individuals with single and multiple diseases and compared to non-diseased animals to identify DMRs associated with transgenerational disease transmission. The exposure of gestating female rats to a permethrin and DEET pesticide combination promoted testis disease, prostate disease, kidney disease, and the presence of multiple disease in the subsequent great-grand offspring F3 generation. Interestingly, the majority of the disease specific sperm DMR associated genes were previously found to be linked to relevant disease specific genes.
2020-11-12 | GSE158254 | GEO
Project description:Environmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes suggesting a general alteration in genome activity. Investigation of eleven different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had unique transgenerational transcriptomes. Common cellular pathways and processes were identified among the tissues. A bionetwork analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue specific gene expression and function. A large number of statistically significant over-represented clusters of differentially expressed genes were identified and termed M-bM-^@M-^\Epigenetic Control RegionsM-bM-^@M-^]. Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome appear to in part coordinately regulate these tissue specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes. We used microarrays to determine genes expressed differentially in rats 11 male or female smatic tissues -male heart, kidney, liver, testis, prostate, seminal vesicles; female heart, kidney, liver, ovary, uterus - due to Vinclozolin treatments of their grand-grandmothers. For each of 11 male or female smatic tissues, RNA samples from 2 treatment groups - control (Con) and vinclozolin (Vin) - were compared to each other. Each treatment groups contained 3 biological replica. RNA for each replica was pooled from 2 individual animals.
2012-06-30 | E-GEOD-35839 | biostudies-arrayexpress
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
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
Project description:The current study investigates the direct effects of in utero vinclozolin exposure on the developing rat testis transcriptome. Vinclozolin is a commonly used fungicide in agriculture and is an endocrine disruptor with anti-androgenic activity. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states that include spermatogenic cell defects, prostate disease, kidney disease, and tumor development. An investigation of the molecular actions of vinclozolin was initiated through an analysis of direct actions on the F1 generation embryonic testis development. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Interestingly, genes previously shown to be regulated during normal male sex determination were not altered by vinclozolin treatment. Categorization by major known functions of all 576 genes altered by in utero vinclozolin exposure demonstrates transcription, signaling, cytoskeletal and extra cellular matrix associated transcripts are highly represented. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. For Samples 1-12: We used microarrays to determine genes expressed differentially between control and in utero Vinclozolin treated E13, E14, and E16 rat testis. For Samples 13-16: We used microarrays to determine genes expressed differentially between control and in vitro Vinclozolin treated E13 cultured rat testis. For Samples 17-20: We used microarrays to determine genes expressed differentially between control and in vitro Flutamide treated rat E13 cultured testis.
2010-02-14 | GSE20245 | GEO
Project description:The current study investigates the direct effects of in utero vinclozolin exposure on the developing rat testis transcriptome. Vinclozolin is a commonly used fungicide in agriculture and is an endocrine disruptor with anti-androgenic activity. Previous studies have demonstrated that exposure to vinclozolin during embryonic gonadal sex determination induces epigenetic modifications of the germ line and transgenerational adult onset disease states that include spermatogenic cell defects, prostate disease, kidney disease, and tumor development. An investigation of the molecular actions of vinclozolin was initiated through an analysis of direct actions on the F1 generation embryonic testis development. Microarray analyses were performed to compare control and vinclozolin treated testis transcriptomes at embryonic day 13, 14 and 16. A total of 576 differentially expressed genes were identified and the major cellular functions and pathways associated with these altered transcripts were examined. The sets of regulated genes at the different development periods were found to be transiently altered and distinct. Interestingly, genes previously shown to be regulated during normal male sex determination were not altered by vinclozolin treatment. Categorization by major known functions of all 576 genes altered by in utero vinclozolin exposure demonstrates transcription, signaling, cytoskeletal and extra cellular matrix associated transcripts are highly represented. Specific cellular process and pathway analyses suggest the involvement of Wnt and calcium signaling, vascular development and epigenetic mechanisms as potential mediators of the direct F1 generation actions of vinclozolin. For Samples 1-12: We used microarrays to determine genes expressed differentially between control and in utero Vinclozolin treated E13, E14, and E16 rat testis. For Samples 13-16: We used microarrays to determine genes expressed differentially between control and in vitro Vinclozolin treated E13 cultured rat testis. For Samples 17-20: We used microarrays to determine genes expressed differentially between control and in vitro Flutamide treated rat E13 cultured testis. For Samples 1-12: RNA samples from two control groups are compared to two Vinclozolin treated groups for each E13, E14, E16 testis. For Samples 13-16: RNA samples from two control groups of E13 cultured testis are compared to two Vinclosolin treated groups of E13 cultured testis. For Samples 17-20: RNA samples from two control groups of E13 cultured testis are compared to two Flutamide treated groups of E13 cultured testis.
2010-02-24 | E-GEOD-20245 | biostudies-arrayexpress
Project description:Environmentally induced epigenetic transgenerational inheritance of adult onset disease involves a variety of phenotypic changes suggesting a general alteration in genome activity. Investigation of eleven different tissue transcriptomes in male and female F3 generation vinclozolin versus control lineage rats demonstrated all tissues examined had unique transgenerational transcriptomes. Common cellular pathways and processes were identified among the tissues. A bionetwork analysis identified gene modules with coordinated gene expression and each had unique gene networks regulating tissue specific gene expression and function. A large number of statistically significant over-represented clusters of differentially expressed genes were identified and termed “Epigenetic Control Regions”. Combined observations demonstrate that all tissues derived from the epigenetically altered germ line develop transgenerational transcriptomes unique to the tissue, but common epigenetic control regions in the genome appear to in part coordinately regulate these tissue specific transcriptomes. This systems biology approach provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes. We used microarrays to determine genes expressed differentially in rats 11 male or female smatic tissues -male heart, kidney, liver, testis, prostate, seminal vesicles; female heart, kidney, liver, ovary, uterus - due to Vinclozolin treatments of their grand-grandmothers.
2012-07-01 | GSE35839 | GEO
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