DNA methylation is correlated with gene expression during early pregnancy in Bos taurus

Coordinated regulation of endometrial gene expression is essential for successful pregnancy establishment. A nonreceptive 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. The correlation between DNA methylation and gene expression was tested. Endometrial samples from fertile and subfertile 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 previously published transcription profiles. 39% of DNA methylation probes assayed mapped to RefSeq genes with transcription measurements. Correlations among gene expression and DNA methylation were assessed, and the 1,000 most significant correlations 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 pregnant and cycling animals were compared, and 11% were differentially expressed when pregnant fertile and subfertile animals were compared. 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.