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Transcriptome profiling of Drosophila adults from multiple generations including flies with genetically-ablated insulin-producing cells as founders.

ABSTRACT: Transgenerational epigenetic inheritance is a subject of immense current interest. In a newly developed Drosophila model in the laboratory, genetic ablation of insulin-producing cells (IPCs) was found to affect whole -body triglyceride levels not only in the ablated flies but also in their male-line derived, non-ablated future generations. To further characterize this genetic-factor-induced transgenerational inheritance model, we have now performed whole body microarray gene expression profiling of adult males and females with genetically ablated IPCs, and of three consecutive, paternally derived non-ablated generations of adult males and females originating from ablated males. Interestingly, like altered levels of triglycerides, transcriptomic alterations are found not only in the ablated flies but also in their male-line-derived, non-ablated future generations.

ORGANISM(S): Drosophila melanogaster

PROVIDER: GSE184339 | GEO | 2023/04/21

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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Transcriptome profiling of Drosophila adults from multiple generations including flies with genetically-ablated insulin-producing cells as founders.

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