Acrylamide modulates the mouse epididymal proteome to drive alterations in the sperm small non-coding RNA profile and dysregulate embryo development
Natalie A. Trigg,
David A. Skerrett-Byrne,
Miguel J. Xavier,
Wei Zhou,
Amanda L. Anderson,
Simone J. Stanger,
Aimee L. Katen,
Geoffry N. De Iuliis,
Matthew D. Dun,
Shaun D. Roman,
Andrew L. Eamens,
Brett Nixon
Affiliations
Natalie A. Trigg
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
David A. Skerrett-Byrne
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
Miguel J. Xavier
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
Wei Zhou
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, VIC 3052, Australia; Gynaecology Research Centre, The Royal Women’s Hospital, Parkville, VIC 3052, Australia
Amanda L. Anderson
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
Simone J. Stanger
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
Aimee L. Katen
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Priority Research Centre for Drug Development, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia
Geoffry N. De Iuliis
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
Matthew D. Dun
Cancer Signalling Research Group, School of Biomedical Sciences and Pharmacy, Faculty of Health and Medicine, University of Newcastle, Callaghan, NSW 2308, Australia; Priority Research Centre for Cancer Research Innovation and Translation, Hunter Medical Research Institute, Lambton, NSW 2305, Australia
Shaun D. Roman
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Priority Research Centre for Drug Development, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW 2308, Australia
Andrew L. Eamens
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia
Brett Nixon
Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, NSW 2308, Australia; Hunter Medical Research Institute, New Lambton Heights, NSW 2305, Australia; Corresponding author
Summary: 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.
