Virtual Presentation SRB Virtual Awards 2020

Acrylamide exposure drives alterations to the small RNA landscape of mature mouse spermatozoa and influences early embryo gene expression.  (#6)

Natalie A Trigg 1 2 , David A Skerrett-Byrne 1 2 , Miguel J Xavier 1 2 , Wei Zhou 1 2 , Amanda L Anderson 1 2 , Simone J Stanger 1 2 , Geoffry N De Iuliis 1 2 , Shaun D Roman 1 2 3 , Andrew L Eamens 1 2 , Brett Nixon 1 2
  1. Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia
  2. Hunter Medical Research Institute, New Lambton Heights, NSW, Australia
  3. Priority Research Centre for Drug Development, School of Environmental and Life Sciences, University of Newcastle, Callaghan, NSW, Australia

Mature spermatozoa harbour a unique population of small non-coding RNAs (sncRNAs), which are delivered to the oocyte upon fertilisation, and thereafter, influence embryonic development and offspring health. Recently, it has been revealed that diverse environmental and lifestyle factors are capable of reprogramming this epigenetic code, with significant post-fertilisation consequences. Despite this knowledge, there remains limited understanding of how paternal exposures influence the remodelling of the sperm sncRNA landscape. To address this question, here we assessed the impact of exposure to the xenobiotic, acrylamide on the global sncRNA profile of mouse spermatozoa. In doing so, we confirmed the acute sensitivity of the sperm sncRNA payload to environmental insult encountered during their post-testicular development. Specifically, we identified 569 sncRNAs (equating to 2.5% of all sncRNAs) that were significantly altered in the mature spermatozoa of acrylamide-exposed males; with the microRNA (miRNA) subclass being most influenced. Further, we have traced the differential accumulation of miRNAs to coincide with sperm transit of the proximal (caput) epididymal segment. Indeed, we identified equivalent miRNA alterations in the extracellular vesicles (EVs) secreted by the caput epididymis following acrylamide exposure; highlighting the important role of EV-mediated communication in driving sperm sncRNA changes following environmental insult. To determine the downstream consequences of these changes in sperm-borne sncRNA, we examined the transcriptome of 2-cell embryos fertilised by the spermatozoa of acrylamide-exposed males. Such analyses revealed altered profiles of gene expression in embryos fertilised by exposed sperm. Among the dysregulated genes, 22 mRNA targets of the increased miRNAs were significantly, and reciprocally, down-regulated in embryos (P<0.05); including multiple genes implicated in embryo development. Overall, these data shed new light on the impact of acute acrylamide exposure on the sncRNA profile of spermatozoa and provide a mechanistic explanation for the increased levels of embryonic loss witnessed in offspring sired by acrylamide-exposed male mice.