Genome-Wide Methylation Profiles Changes Associated with Stress Exposure in Cattle

Stress has a detrimental impact on dairy cattle health, welfare and productivity. Its impact on gene expression, metabolism and immune response has been investigated but little is known on the epigenetic mechanisms mediating the effect of stress at the cellular and organism level.

To assess how different levels of stress exposure affect epigenetic regulation mechanisms in cattle, we investigated genome-wide DNA methylation in 20 Italian Red Pied dairy cows falling in the plus- and minus-variant tails of the distribution of milk cortisol concentration (MC), a neuroendocrine biomarker of stress in dairy cows, measured in 180 animals belonging to the same farm in the framework of the Gen2Phen Italian project. The ‘low-’ and ‘high-cortisol’groups of animals had MC<370 pg/ml and>810 pg/ml, respectively. Their methylome was analysed by Reduced Representation Bisulfite Sequencing which provides single-base resolution methylation profiles across the whole genome.

To date, 20 animals (10 low- and 10 high-MC) have been sequenced and an average of 22.5 million reads were produced per sample, with varying mapping efficiency (18.0-33.6%). The two groups showed similar proportion of methylation at CpG sites, while they differed at non-CpG sites.

Significant methylation changes were observed in 970 regions and 109 genes. KEGG pathway analyses indicated that these genes were mainly involved in glucocorticoids metabolism, stress responses,cellular defense and calcium signaling pathways.

These preliminary results suggest that stress response in livestock is mediated by epigenetic regulation, provide target biomarkers to assess the effect of stress-mitigation management procedures and candidate genes for the selection of stress-tolerant animals.