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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

Lookup NU author(s): Dr Miguel Garcia Dos Santos XavierORCiD

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Abstract

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 coincide with sperm transit of the proximal (caput) segment of the epididymis, wherein acrylamide exposure alters the abundance of several transcription factors implicated in the expression of acrylamide-sensitive sncRNAs. We also identify extracellular vesicles secreted from the caput epithelium in relaying altered sncRNA profiles to maturing spermatozoa and dysregulated gene expression during early embryonic development following fertilization by acrylamide-exposed spermatozoa. These data provide mechanistic links to account for how environmental insults can alter the sperm epigenome and compromise the transcriptomic profile of early embryos.


Publication metadata

Author(s): Trigg NA, Skerrett-Byrne DA, Xavier MJ, Zhou W, Anderson AL, Stanger SJ, Katen AL, De Iuliis GN, Dun MD, Roman SD, Eamens AL, Nixon B

Publication type: Article

Publication status: Published

Journal: Cell Rep

Year: 2021

Volume: 37

Issue: 1

Pages: 109787

Print publication date: 05/10/2021

Online publication date: 05/10/2021

Acceptance date: 09/09/2021

ISSN (electronic): 2211-1247

Publisher: Elsevier

URL: https://doi.org/10.1016/j.celrep.2021.109787

DOI: 10.1016/j.celrep.2021.109787


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