161 Prediction of subclinical endometritis in postpartum dairy cows from circulating cell-free miRNA profiles
Résumé
Application: Current diagnosis of subclinical endometritis (SCE), relying today on invasive uterine cytology and/or biopsy sampling, would benefit from the use of blood-based diagnostic biomarkers.
Introduction: Subclinical endometritis is an unresolved inflammation of the endometrium of postpartum dairy cows, affecting fertility. Due to the role of miRNAs in disease development and their use as markers in other species, this study evaluated the cell-free circulating miRNA profiles of SCE cows and their value as blood-based diagnostic biomarkers.
Materials and Methods: Healthy (H, n = 6) and SCE (n = 11) cows characterized by endometrial cytology and biopsy were blood sampled at 21 and 44 days postpartum. These cows are a subset of the animals enrolled in a larger study regarding SCE. Following extraction of cell-free plasma miRNAs and RNA-seq analysis, differential abundance analysis of miRNAs was performed with the DESeq2 R package (adjusted p-value of 0.05), and discriminant analysis was used to combine the differently abundant miRNAs in a single variable and create a predictive model.
Results: 34 miRNAs with differential abundance between H and SCE cows were identified. From these, 22 were more abundant and 12 were less abundant in SCE than in H cows. No main effect of the postpartum stage was observed. Overall, when used as a stand-alone SCE marker, no miRNA provided a good prediction of the diseased animals. Stepwise discriminant analysis revealed that among these 34 differently abundant miRNAs, miR425-3p, miR151-3p, and miR30b-5p contributed most to the identification of H and SCE animals. The combination of these three miRNAs in a single variable from subsequent canonical analysis allowed the prediction of the health status in 15/17 (88%) animals at 21 days postpartum. This canonical variable presented a sensitivity and specificity of 90.9% and 83.3%, respectively.
Conclusions: Although apparently confined to the endometrium, SCE is associated with distinct circulating miRNA profiles. Despite the fact that no individual miRNA presented a reasonable prediction of the disease as a stand-alone marker, the present results show that it is possible to combine multiple miRNAs to develop a blood-based diagnostic biomarker of SCE with acceptable accuracy.