Genome-wide transcriptional and DNA methylation profiling of the bovine endometrium

Abstract

The aim of this research was to identify key molecular mechanisms regulating early pregnancy events in dairy cattle. Genome-wide gene expression and DNA methylation profiles were characterised in the endometrium of fertile and sub-fertile dairy cows at day 17 of pregnancy and the oestrous cycle. Gene expression data in combination with QTL data was then used to identify candidate genes for genetic analysis. The results of this study identified several biological processes likely to be important contributors to pregnancy success. In particular, genes classified as having roles in immune response were upregulated in pregnant animals and down-regulated in sub-fertile animals. Additionally, gene expression was correlated with DNA methylation in several genes in these pathways. Lastly, QTL for fertility traits were identified on chromosome 9. Genes located in the QTL region were identified and cross-referenced with the genes identified as differentially expressed in fertile and sub-fertile dairy cows. The most differentially expressed gene was chosen as a candidate gene for genetic analysis. However, no association of polymorphisms in this gene with fertility phenotypes was detected. The results of this research have identified several genes in biologically relevant pathways that are influenced by the presence of the embryo. Further, many of these genes demonstrate differential expression in fertile and sub-fertile dairy cows. Modulation of the maternal immune system is highlighted as a potentially important process required for pregnancy success. The expression profiles of genes in these pathways suggest that insufficient tolerance to the embryo may contribute to pregnancy loss in the sub-fertile dairy cow strain. The differential regulation of these genes could be the consequence of genetic or epigenetic regulation. For example, there is evidence that DNA methylation may contribute to regulation of gene expression in response to the embryo and could account for some of the differences identified in the two strains studied. Alternatively, genetic variation could underlie these differences. This study has identified several important biological pathways and potential regulatory mechanisms that warrant further investigation.