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The transgenerational effects of pesticide chlordecone on prostate

ABSTRACT: The environmental factors such as pesticides could affect the developmental processes and cause the phenotypic changes. Moreover, the changes could be transferred to a subsequent generation via gametes. In this project we studied whether the pesticide chlordecone could cause the developmental effects and cause the transgenerational inheritance in outbred mouse strain (Swiss). Mice were treated during development (E6.5-E15.5) at dose 100 µg/kg/day and the progeny of exposed mice (F1) were crossed for three generations. The prostate of the first (F1) and third generation males (F3) were used for RNA-seq-analysis. We used three biological replicates for each condition.

ORGANISM(S): Mus musculus

PROVIDER: GSE135200 | GEO | 2021/04/01

REPOSITORIES: GEO

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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.

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The transgenerational effects of pesticide chlordecone on prostate

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