Acrylamide modulates the mouse epididymal proteome to drive alterations to the sperm epigenome and dysregulate embryo development

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. 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 abundance 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, and dysregulated gene expression during early embryonic development following fertilisation 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. Overall design: Examination of the small non-protein coding RNA profile in mature sperm from control and acrylamide exposed mice using next generation sequencing in duplicate. Examination of the transcriptome of 2-cell embryos that developed from zygotes fertilised by three different populations of spermatozoa (control, epididymal acrylamide exposure and spermatocyte acrylamide exposure) in triplicate.