Prenatal transportation stress alters genome-wide DNA methylation in suckling Brahman bull calves1,2

Abstract

The objective of this experiment was to identify genome-wide differential methylation of DNA in young prenatally stressed (PNS) bull calves. Mature Brahman cows (n = 48) were transported for 2-h periods at 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 d of gestation or maintained as nontransported Controls (n = 48). Methylation of DNA from white blood cells from a subset of 28-d-old intact male offspring (n = 7 PNS; n = 7 Control) was assessed via reduced representation bisulfite sequencing. Samples from PNS bulls contained 16,128 CG, 226 CHG, and 391 CHH (C = cytosine; G = guanine; H = either adenine, thymine, or cytosine) sites that were differentially methylated compared to samples from Controls. Of the CG sites, 7,407 were hypermethylated (at least 10% more methylated than Controls; P ≤ 0.05) and 8,721 were hypomethylated (at least 10% less methylated than Controls; P ≤ 0.05). Increased DNA methylation in gene promoter regions typically results in decreased transcriptional activity of the region. Therefore, differentially methylated CG sites located within promoter regions (n = 1,205) were used to predict (using Ingenuity Pathway Analysis software) alterations to canonical pathways in PNS compared with Control bull calves. In PNS bull calves, 113 pathways were altered (P ≤ 0.05) compared to Controls. Among these were pathways related to behavior, stress response, metabolism, immune function, and cell signaling. Genome-wide differential DNA methylation and predicted alterations to pathways in PNS compared with Control bull calves suggest epigenetic programming of biological systems in utero.

Preconditioning beef cattle for long-duration transportation stress with rumen-protected methionine supplementation: A nutrigenetics study

“…In a previous study, prenatal transportation stress in Brahman bull calves was assessed at the methylome level. Results showed at least 10% more methylation in stressed calves as compared to controls [104]. In our study, RPM produce the inhibition of AHCY during preconditioning.…”

Environment-driven reprogramming of gamete DNA methylation occurs during maturation and is transmitted intergenerationally in salmon

“…Glutamatergic signalling is an important excitory driver of the hypothalamic-pituitary-adrenal (HPA) axis that, among other functions, mediates organismal stress responses and aggression and it has been hypothesized that selection on these pathways underlies “tameness” in domesticated animals and attenuated stress responses under crowded conditions (O’Rourke and Boeckx 2020). Furthermore, differential methylation of glutamate receptors has been reported in response to prenatal stress in cows (Littlejohn et al 2018) and is associated with adverse behavioural phenotypes in preterm infant humans (Everson et al 2019). This raises the hypothesis that adult SAS fish could transmit information about the crowding they experienced prior to spawning to their offspring in order to prime them for a highly competitive environment upon hatching (Christie et al 2012).…”

Adrenergic Tone as an Intermediary in the Temperament Syndrome Associated With Flight Speed in Beef Cattle

“…Repeated transport of brahman cows for 2 h at 60 ± 5, 80 ± 5, 100 ± 5, 120 ± 5, and 140 ± 5 d of gestation was associated with a significant increase in FS and basal cortisol in calf progeny in comparison to controls (Littlejohn et al, 2016). Analysis of genome-wide distribution of differential DNA methylation (hypermethylation and hypomethylation) in peripheral blood leukocytes revealed alterations in canonical pathways of behavior, stress responses, metabolism, and immune function (Littlejohn et al, 2018). In a more focused analysis, differential methylation was observed in pathways involved in opioid signaling, corticotropin releasing hormone signaling, dopamine signaling, serotonin signaling, and GABA signaling (Littlejohn et al, 2020).…”