BisPCRSeq analysis of ribosomal DNA in mouse sperm exposed to protein restriction during different critical time windows. BisPCRSeq analysis of ribosomal DNA in mouse sperm exposed to protein restriction during different critical time windows

Background: Environmental influences fluctuate throughout the life course of an organism. It is therefore important to understand how the timing of exposure impacts the molecular response. Here we examine the responses of two key molecular markers of dietary stress – variant-specific methylation at ribosomal DNA (rDNA) and small RNA distribution including tRNA fragments – in a mouse model of protein restriction (PR) with exposures pre- and/or post-weaning. Results: We first confirm that pre-weaning PR exposure modulates the methylation state of rDNA in a genotype-dependent manner whereas post-weaning PR exposure has no such effect. Conversely, post-weaning PR induces a shift in small RNA distribution, but there is no effect in the pre-weaning PR model. Intriguingly, mice exposed to PR throughout their lives show neither of these two dietary stress markers, similar to controls. Overall design: sperm DNA from four different diet groups (CTCT, CTPR, PRCT and PRPR) with all males from each litter being represented