Epigenome-Wide Association Study for Pesticide (Permethrin and DEET) Induced DNA Methylation Epimutation Biomarkers for Specific Transgenerational Disease
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE158254 | GEO | 2020/11/12
REPOSITORIES: GEO
Similar Datasets
Project description:Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a M-bM-^@M-^\pesticide mixtureM-bM-^@M-^] (pesticide permethrin and insect repellent N,N-Diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures. Methylated sperm DNA was isolated from rats ancestrally exposed to pesticides (Pip). Three independent samples from the treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays (Pip1/Cip1, Pip2/Cip2, and Pip3/Cip3), resulting in three arrays for the treatment.
2014-07-22 | E-GEOD-59554 | biostudies-arrayexpress
Project description:Environmental compounds are known to promote epigenetic transgenerational inheritance of disease. The current study was designed to determine if a “pesticide mixture” (pesticide permethrin and insect repellent N,N-Diethyl-meta-toluamide, DEET) promotes epigenetic transgenerational inheritance of disease and associated DNA methylation epimutations in sperm. Gestating F0 generation female rats were exposed during fetal gonadal sex determination and the incidence of disease evaluated in F1 and F3 generations. There were significant increases in the incidence of total diseases in animals from pesticide lineage F1 and F3 generation animals. Pubertal abnormalities, testis disease, and ovarian disease (primordial follicle loss and polycystic ovarian disease) were increased in F3 generation animals. Analysis of the pesticide lineage F3 generation sperm epigenome identified 363 differential DNA methylation regions (DMR) termed epimutations. Observations demonstrate that a pesticide mixture (permethrin and DEET) can promote epigenetic transgenerational inheritance of adult onset disease and potential sperm epigenetic biomarkers for ancestral environmental exposures.
2014-07-22 | GSE59554 | GEO
Project description:Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Methylated sperm DNA was isolated from rats ancestrally exposed to methoxychlor. Three independent samples from each treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays, resulting in three arrays for the treatment.
2014-05-30 | E-GEOD-58091 | biostudies-arrayexpress
Project description:Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.
2014-05-30 | GSE58091 | GEO
Project description:Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease. Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease. Methylated sperm DNA was isolated from rats ancestrally exposed to plastics (Bip), vinclozolin (Vip), pesticides (Pip), dioxin (Hip), jet fuel (Jip) or control vehicle (Cip). Three independent samples from each treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. For each treatment, treated samples were paired with control samples and hybridized together on arrays (Bip1/Cip1, Bip2/Cip2, Bip3/Cip3, Vip1/Cip1, etc.), resulting in three arrays per treatment group.
2014-05-16 | E-GEOD-57693 | biostudies-arrayexpress
Project description:One of the most widely used agricultural compounds worldwide is the herbicide glyphosate (N-(phosphonomethyl)glycine), commonly known as Roundup. The current study using a transient exposure of gestating F0 generation female rats found negligible impacts of glyphosate on the directly exposed F0 generation or F1 generation offspring, but dramatic increases in pathologies in the F2 generation grand-offspring and F3 transgenerational great-grand-offspring. The transgenerational pathologies observed include prostate disease, obesity, kidney disease, ovarian disease, and parturition (birth) abnormalities. Epigenetic analysis of the F1, F2 and F3 generation sperm identified altered DNA methylation.
2019-04-25 | GSE118557 | GEO
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.
2021-03-16 | GSE163412 | GEO
Project description:Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease. Environmental factors during fetal development can induce a permanent epigenetic change in the germ line (sperm) that then transmits epigenetic transgenerational inheritance of adult-onset disease in the absence of any subsequent exposure. The epigenetic transgenerational actions of various environmental compounds and relevant mixtures were investigated with the use of a pesticide mixture (permethrin and insect repellant DEET), a plastic mixture (bisphenol A and phthalates), dioxin (TCDD) and a hydrocarbon mixture (jet fuel, JP8). After transient exposure of F0 gestating female rats during the period of embryonic gonadal sex determination, the subsequent F1-F3 generations were obtained in the absence of any environmental exposure. The effects on the F1, F2 and F3 generations pubertal onset and gonadal function were assessed. The plastics, dioxin and jet fuel were found to promote early-onset female puberty transgenerationally (F3 generation). Spermatogenic cell apoptosis was affected transgenerationally. Ovarian primordial follicle pool size was significantly decreased with all treatments transgenerationally. Differential DNA methylation of the F3 generation sperm promoter epigenome was examined. Differential DNA methylation regions (DMR) were identified in the sperm of all exposure lineage males and found to be consistent within a specific exposure lineage, but different between the exposures. Several genomic features of the DMR, such as low density CpG content, were identified. Exposure-specific epigenetic biomarkers were identified that may allow for the assessment of ancestral environmental exposures associated with adult onset disease.
2014-05-16 | GSE57693 | GEO
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.
2017-08-08 | GSE98683 | GEO
Project description:Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. Methylated sperm DNA was isolated from rats ancestrally exposed to dioxin (Hip). Three independent samples from the treatment group were obtained. Differential DNA methylation between treatment groups was determined using Nimblegen microarrays. Treated samples were paired with control samples and hybridized together on arrays (Hip1/Cip1, Hip2/Cip2, and Hip3/Cip3), resulting in three arrays for the treatment.
2014-07-22 | E-GEOD-59552 | biostudies-arrayexpress