Dataset Information

The reproductive toxicant acrylamide modulates the mouse epididymal proteome to drive alterations to the sperm epigenome and dysregulate embryo development.

ABSTRACT: Paternal exposure to a range of environmental and lifestyle factors elicits distinct changes to the sperm sncRNA profile; modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures effect the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the potent reproductive toxicant, acrylamide. Further, we traced the differential accumulation of acrylamide responsive sncRNAs to coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure altered the expression of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identified extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa, the implications of which manifest in the form of dysregulated gene expression during early embryonic development. These data provide a causative mechanistic link to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos.

ORGANISM(S): Mus Musculus

SUBMITTER: David Skerrett-Byrne

PROVIDER: PXD022876 | panorama | Fri Oct 08 00:00:00 BST 2021

REPOSITORIES: PanoramaPublic

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Publications

Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development.

Trigg Natalie A NA Skerrett-Byrne David A DA Xavier Miguel J MJ Zhou Wei W Anderson Amanda L AL Stanger Simone J SJ Katen Aimee L AL De Iuliis Geoffry N GN Dun Matthew D MD Roman Shaun D SD Eamens Andrew L AL Nixon Brett B

Cell reports 20211001 1

Paternal exposure to environmental stressors elicits distinct changes to the sperm sncRNA profile, modifications that have significant post-fertilization consequences. Despite this knowledge, there remains limited mechanistic understanding of how paternal exposures modify the sperm sncRNA landscape. Here, we report the acute sensitivity of the sperm sncRNA profile to the reproductive toxicant acrylamide. Furthermore, we trace the differential accumulation of acrylamide-responsive sncRNAs to coin ...[more]

PMID: 34610313

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Project description:For evaluating genotoxic exposure in human populations a number of biomarkers has been successfully applied over the last 30 years to determine early biological effects due to exposure to carcinogens. Despite their success, these early biological effects markers provide limited mechanistic insight, and are unable to detect exposure to non-genotoxic carcinogens. Gene expression profiling forms a promising tool for the development of new biomarkers in blood cells to overcome these limitations. The aim of our research was to identify novel genomics-based candidate markers for genotoxic and non-genotoxic carcinogen exposure. Whole genome gene expression changes were investigated in human blood cells following ex vivo exposure to a range of genotoxic and non-genotoxic carcinogenic compounds using whole genome microarrays. Sets of genes, as well as biological pathways indicative of genotoxic exposure and of non-genotoxic carcinogenic exposure were identified. Furthermore, networks were built using the genotoxic and non-genotoxic genes sets, showing the majority of the genes to be interlinked and revealing distinctive transcription factors for both classes. The identification of these potential candidate marker genes might contribute to the development of genomic based biomakers of genotoxic exposure, and possibly even more importantly biomarkers of exposure to non-genotoxic carcinogens since presently no biomarkers are available. Keywords: Genome wide gene expression analysis, Transcriptomic profile indicative of immunotoxic exposure For analysis of whole genome gene expression by microarray, PBMC from five independent donors per compound were exposed for 20 hours to three concentrations, i.e. the 100% and two serial ten-fold dilutions (10% and 1%), and a DMSO or PBS vehicle control. Exposed samples were always labelled with Cy5, whereas the vehicle control samples were labelled with Cy3, and were competetively hybridized on 4x44K Agilent microarrays.

Dataset Information

The reproductive toxicant acrylamide modulates the mouse epididymal proteome to drive alterations to the sperm epigenome and dysregulate embryo development.

Publications

Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development.

Similar Datasets

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