Influence of prenatal transportation stress-induced differential DNA methylation on the physiological control of behavior and stress response in suckling Brahman bulls calves

Authors: LITTLEJOHN, BRITTNI - Texas A&M Agrilife; PRICE, DEBBI - Texas A&M Agrilife; NEUENDORFF, DON - Texas A&M Agrilife; Carroll, Jeffery - Jeff Carroll; VANN, RHONDA - Mississippi State University; RIGGS, PENNY - Texas A&M University; RILEY, DAVID - Texas A&M University; LONG, CHARLES - Texas A&M Agrilife; RANDEL, RONALD - Texas A&M Agrilife; WELSH, THOMAS - Texas A&M Agrilife

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/5/2019
Publication Date: 12/6/2019
Citation: Littlejohn, B.P., Price, D.M., Neuendorff, D.A., Carroll, J.A., Vann, R.C., Riggs, P.K., Riley, D.G., Long, C.R., Randel, R.D., Welsh, T.H. 2019. Influence of prenatal transportation stress-induced differential DNA methylation on the physiological control of behavior and stress response in suckling Brahman bulls calves. Journal of Animal Science. 98(1):1-18. https://doi.org/10.1093/jas/skz368.
DOI: https://doi.org/10.1093/jas/skz368

Interpretive Summary: Elevated maternal stress hormones during pregnancy have been shown to alter fetal development in several species. Alterations in postnatal behavioral and stress responses are among the most reported outcomes associated with prenatal stress. Prenatal stress alters postnatal outcomes, in part, by altering gene expression through non-genetic influences. However, the impact of exposing livestock to transportation stress during pregnancy is not fully understood. Therefore, a collaborative study was conducted with scientists from Texas A&M University, Mississippi State University, and the USDA-ARS Livestock Issues Research Unit to determine if exposing gestating calves to a prenatal transportation event would affect the postnatal gene expression. Results from this study revealed that transporting pregnant cows for 2 hours resulted in calves whose postnatal behavioral and stress responses and the associated genes were altered compared to calves that did not experience the transportation stress during gestation. Understanding how the prenatal environment shapes postnatal behavioral and stress responses may provide novel opportunities for beef cattle improvement. This information increases the overall scientific knowledge base with regard to understanding of the impact of prenatal stress on economically and biologically relevant traits in cattle, and will be of specific interest to scientists working in the field of beef production and genetics, and to veterinarians and beef cattle producers.

Technical Abstract: The objective of this experiment was to examine potential differential methylation of DNA as a mechanism for altered behavioral and stress responses in prenatally stressed (PNS) compared with non-prenatally stressed (Control) young 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 (Transported group) or maintained as non-transported Controls (n = 48). From the offspring born to Transported and Control cows, a subset of 28-d-old intact bulls (n = 7 PNS; n = 7 Control) were evaluated for methylation of DNA of behavior and stress response associated genes. Methylation of DNA from white blood cells was assessed via reduced representation bisulfite sequencing methods. Because increased methylation of DNA within gene promoter regions has been associated with decreased transcriptional activity of the corresponding gene, differentially methylated (P = 0.05) CG sites (cytosine followed by a guanine nucleotide) 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. Among differentially methylated genes (P = 0.05) related to behavior and the stress response were OPRK1, OPRM1, PENK, POMC, NR3C2, TH, DRD1, DRD5, COMT, HTR6, HTR5A, GABRA4, GABRQ, and GAD2. Among altered (P < 0.05) signaling pathways related to behavior and the stress response were Opioid Signaling, Corticotropin-Releasing Hormone Signaling, Dopamine Receptor Signaling, Dopamine-DARPP32 Feedback in cAMP Signaling, Serotonin Receptor Signaling, and GABA Receptor Signaling. Alterations to behavior and stress response-related genes and canonical pathways supported previously observed elevations in temperament score and serum cortisol through weaning in the larger population of PNS calves from which bulls in this study were derived. Differential methylation of DNA and predicted alterations to behavior and stress response-related pathways in PNS compared with Control bull calves suggest epigenetic programming of behavior and the stress response in utero.