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

INSTRUMENT(S): Q Exactive HF-X

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Caput Epididymis, Epithelial Cell

SUBMITTER: David Skerrett-Byrne

LAB HEAD: Professor Brett Nixon

PROVIDER: PXD022865 | Pride | 2021-10-07

REPOSITORIES: Pride

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			Action	DRS
	20191104_HFX4_DSB_Acryl_TMT_HILIC_F1.raw	Raw
	20191104_HFX4_DSB_Acryl_TMT_HILIC_F10.raw	Raw
	20191104_HFX4_DSB_Acryl_TMT_HILIC_F11.raw	Raw
	20191104_HFX4_DSB_Acryl_TMT_HILIC_F2.raw	Raw
	20191104_HFX4_DSB_Acryl_TMT_HILIC_F3.raw	Raw

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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:Acrylamide is a type-2 alkene monomer with established human neurotoxic effects. While the primary source of human exposure to acrylamide is occupational, other exposure sources include food, drinking water, and smoking. In this study, neurobehavioral assays coupled with transcriptional profiling analysis were conducted to assess both behavioral and gene expression effects induced by acrylamide neurotoxicity in rats when administered during early postnatal life. Acrylamide administration in rat pups induced significant characteristic neurotoxic symptoms including increased heel splay, decrease in grip strength, and decrease in locomotor activity. Transcriptome analysis with the Affymetrix Rat Genome 230 2.0 array indicated that acrylamide treatment caused a significant alteration in the expression of genes involved in muscle contraction, pain regulation, and dopaminergic neuronal pathways. First, in agreement with the observed behavioral effects, expression of the Mylpf gene involved in muscle contraction was downregulated in the spinal cord in response to acrylamide. Second, in sciatic nerves, acrylamide repressed the expression of the opioid receptor gene Oprk1 that is known to play a role in neuropathic pain regulation. Finally, in the cerebellum, acrylamide treatment caused a decrease in the expression of the nuclear receptor gene Nr4a2 that is required for development of dopaminergic neurons. Thus, our work examining the effect of acrylamide at the whole-genome level on a developmental mammalian model has identified novel genes previously not implicated in acrylamide neurotoxicity that can be further developed into biomarkers for assessing the risk of acrylamide exposure. Three-week-old male Wistar rat pups were treated with either acrylamide or saline daily (30 mg/kg) for 21 days, then tissues (cerebellum, spinal cord, and sciatic nerve) were harvested and frozen. Two biological replicate samples, each sample consisting of pooled tissue from 2 rats, were analyzed for each treatment.