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Genome-wide DNA methylation in cows subjected to different stress level as assessed by cortisol in milk

ABSTRACT: 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 high- and low-variant tails of the distribution of milk cortisol concentration (MC), a neuroendocrine biomarker of stress in dairy cows, measured in 126 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. The two groups showed similar proportion of methylation at CpG sites, while they differed at non-CpG sites. Significant methylation changes were observed in 897 regions and 248 genes. KEGG and Gene Ontology (GO) pathway analyses indicated that these genes were mainly involved in immune regulatory pathways, glucocorticoids metabolism and nervous system functions. These preliminary results suggest that cortisol secretion in livestock is mediated by epigenetic regulation, provide target biomarkers to assess the effect of stress management procedures and candidate genes for the selection of stress-tolerant animals.

ORGANISM(S): Bos taurus

PROVIDER: GSE146877 | GEO | 2020/09/30

REPOSITORIES: GEO

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Project description:Co-ordinated regulation of endometrial gene expression is essential for successful pregnancy establishment. A non-receptive uterine environment may be a key contributor to pregnancy loss, as the majority of pregnancy losses occur prior to embryo implantation. DNA methylation has been highlighted as a potential contributor in regulating early pregnancy events in the uterus. It was hypothesized that DNA methylation regulates expression of key genes in the uterus during pregnancy. To gain support for this hypothesis the correlation between DNA methylation and gene expression was tested. Endometrial samples from fertile and sub-fertile dairy cow strains were obtained at day 17 of pregnancy or the reproductive cycle. Microarrays were used to characterize genome-wide DNA methylation profiles and data compared with transcription profiles which have been previously reported. 39% of DNA methylation probes assayed mapped to RefSeq genes with transcription measurements. The 1,000 most significant correlations were used for subsequent analysis. Of these, 52% percent were negatively correlated with gene expression. When this gene list was compared with previously reported gene expression studies on the same tissues, 42% were differentially expressed when comparing pregnant and cycling animals and 11% were differentially expressed comparing pregnant fertile and sub-fertile animals. DNA methylation status was correlated with gene expression in several pathways implicated in early pregnancy events. Although these data do not provide direct evidence of a causative association between DNA methylation and gene expression, this study provides critical support for an effect of DNA methylation in early pregnancy events and highlights candidate genes for future studies. The estrous cycles of 24 lactating dairy cows were synchronized (at 58.8 (SEM 3.77) and 60.2 (SEM 1.51) days post calving in dairy cows of sub-fertile and fertile strains, respectively) and 14 received a single embryo transferred on day 7 of the estrous cycle. Animals were slaughtered at day 17 of the reproductive cycle and endometrial tissues (both caruncular and intercaruncular) were sampled. Selection criteria for the study included strain and calving date, and health postcalving was an exclusion criterion (cows with severe uterine infections or mastitis were excluded before being enrolled in the embryo transfer round). Cows in each strain were matched for calving number and age. A total of 10 cycling and 12 pregnant animals enrolled in the study were utilized, due to the associated costs of slaughtering the cows. These animals represented fertile (six pregnant and five cycling Holstein-Friesian cows with New Zealand ancestry/M-bM-^IM-$30% North American genetics, n=11, NZ) and sub-fertile (six pregnant and five cycling Holstein-Friesian cows with >87% North American ancestry, n=11, NA) phenotypes of Holstein-Friesian dairy cows

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Genome-wide DNA methylation in cows subjected to different stress level as assessed by cortisol in milk

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