PSV-7 - Evaluation of prenatal transportation stress on methylomics and transcriptomics in the stress axis tissues of mature Brahman cows

Abstract: Prenatal stress is known to alter the postnatal methylome and transcriptome of offspring, resulting in various physiological disorders. In Brahman cattle that experienced prenatal transportation stress (PNS), differential DNA methylation was detected for genes related to behavior, stress, and immune response within lymphocytes at 28 days and 5 years of age. The objective of this study was to determine whether PNS affected DNA methylation (DNAm), as well as gene expression, within key stress axis tissues of mature Brahman cows. Samples were collected from the paraventricular nucleus (PVN), anterior pituitary (PIT), adrenal cortex (AC), and adrenal medulla (AM) of 5-year-old Brahman cows whose dams were either exposed to transportation during gestation (PNS, n=6) or were not transported (Control, n=8). Total DNA and RNA were isolated for genome-wide DNAm and RNA-Seq analyses, respectively, and differential analyses were conducted using the edgeR package. Gene ontology (GO) and KEGG pathway enrichment analysis of differentially methylated genes (DMG) and differentially expressed genes (DEG) within each sample tissue were conducted with the DAVID Functional Annotation Tool. In PNS cows compared to Controls there were 3, 64, 99, and 37 hypomethylated and 2, 93, 90, and 36 hypermethylated genes (FDR< 0.15) within the PVN, PIT, AC, and AM, respectively. There were no DEG within the AM, while the PVN, PIT, and AC had 6, 25, and 5 up-regulated genes (FDR< 0.15), respectively, and the PIT had 24 down-regulated genes (FDR< 0.15) in PNS cows relative to Control cows. For the DMG, the PVN revealed no enriched terms, while the PIT, AC, and AM had both GO (46, 45, and 14, respectively) and KEGG (12, 7, and 3, respectively) enriched terms. For the DEG, the PVN, PIT, and AC had 4, 24, and 12 GO enriched terms, respectively, while only the PVN and AC had 3 and 2 KEGG enriched terms, respectively. Results suggest that the methylome and transcriptome were altered in each stress axis tissue of the mature PNS Brahman cows, with several potentially modulated cellular processes, including actin cytoskeleton maintenance, neurodevelopment, and synaptic function, as well as cell motility, survival, and homeostasis. There was no overlap of individual genes in the DMG and DEG datasets; however, there was an overlap in enriched GO and KEGG terms between stress axis tissues regardless of dataset type, particularly those related to the actin cytoskeleton, signal transduction, cellular homeostasis, and synaptic transmission. Overall, the PIT, AC, and AM demonstrated a potential impairment of these cellular processes, while the PVN demonstrated a potential promotion of actin cytoskeleton maintenance. This study gives a first assessment of overall methylomic and transcriptomic alterations within the stress axis tissues due to PNS, as well as hints at potential long-term consequences of prenatal stress in cattle.