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

Amy Brewer,Paul Cormican,Aspinas Chapwanya,Joseph J Lim,Kieran G Meade,Cliona O’Farrelly

doi:10.1038/s41598-020-75104-7

Abstract

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.

Highlights

Following calving, the cow must undergo the heavily energy-dependent and parallel processes of uterine involution and the initiation of lactation
The most significant detrimental effects have been documented from the development of clinical uterine disease, which is usually diagnosed by a veterinarian after 21 days postpartum (DPP) by the presence of purulent vaginal discharge (PVD)
PVD was shown in this study to significantly increase the calving to conception period (CCP) in all cows, but to a greater extent in cows with a high milk yield in the lactation before disease diagnosis, showing cumulative effects of physiological demand on reproduction indices

Summary

Introduction

The cow must undergo the heavily energy-dependent and parallel processes of uterine involution and the initiation of lactation. Bacterial infection is inevitable after calving, it seems that the local immune system has a remarkable ability to support the development of a protective microbiome and restore homeostasis. In a significant proportion of high performing cows, infection leads to the development of various forms of disease which delays uterine involution, and negatively impacts other aspects of the cow’s productive physiology. The most significant detrimental effects have been documented from the development of clinical uterine disease, which is usually diagnosed by a veterinarian after 21 days postpartum (DPP) by the presence of purulent vaginal discharge (PVD). The energy diverted into immune and inflammatory processes can

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