Qualitative and quantitative differences in endometrial inflammatory gene expression precede the development of bovine uterine disease

The transcriptome of the endometrium early postpartum was profiled to determine if inflammatory gene expression was elevated in cows which subsequently developed uterine disease. Endometrial cytobrush samples were collected at 7 days postpartum (DPP) from 112 Holstein-Friesian dairy cows, from which 27 were retrospectively chosen for RNA-seq on the basis of disease classification [ten healthy and an additional 17 diagnosed with cytological endometritis (CYTO), or purulent vaginal discharge (PVD)] at 21 DPP. 297 genes were significantly differentially expressed between cows that remained healthy versus those that subsequently developed PVD, including IL1A and IL1B (adjusted p < 0.05). In contrast, only 3 genes were significantly differentially expressed in cows which subsequently developed CYTO. Accounting for the early physiological inflammatory status present in cows which do not develop disease enhanced the detection of differentially expressed genes associated with CYTO and further expression profiling in 51 additional cows showed upregulation of multiple immune genes, including IL1A, IL1B and TNFA. Despite the expected heterogeneity associated with natural infection, enhanced activation of the inflammatory response is likely a key contributory feature of both PVD and CYTO development. Prognostic biomarkers of uterine disease would be particularly valuable for seasonal-based dairy systems where any delay to conception undermines sustainability.