Profiles of Specialized Pro-resolving Mediators (SPM) in dairy cows with healthy postpartum or endometritis

In humans and laboratory species, Specialized Pro-Resolving Mediators (SPM), a class of cell-signaling molecules originated from the metabolism of polyunsaturated fatty acids, emerged as mediators of inflammation resolution, but their role in other species remains almost unknown. In dairy cows, postpartum uterine involution involves a physiological transient inflammation, which may evolve into a pathologic inflammation (endometritis). This observational retrospective cohort study characterized the SPM profiles of plasma (2, 10, 21 d postpartum - DPP) and uterine fluid (21 DPP) of healthy cows (n = 19), and their deviations in cows with endometritis (n = 12). Compared with healthy cows, at 21 DPP, cows with endometritis showed greater uterine cytology proportion of neutrophils, macrophages, M2 phenotype macrophages, and uterine fluid concentrations of the inflammatory mediators PGE2 (7360.7 vs. 2647.6 pg/mL), LTB4 (36.5 vs. 16.4 pg/mL) and chemerin (1.6 vs. 1.3 pg/mL). This indicates that in healthy cows the endometrial inflammatory stimuli already declined by 21 DPP, whereas in cows with endometritis, inflammation was active. Compared with healthy cows, at 21 DPP, cows with endometritis showed greater uterine fluid concentrations of the SPM 18-HEPE (42.2 vs. 19.8 pg/mL), RvE2 (2.7 vs. 1.1 pg/mL) and RvE4 (1.5 vs. 0.5 pg/mL). This may indicate that in healthy cows the pro-resolving mechanisms were already declining, as inflammation is controlled, whereas in cows with endometritis the pro-resolving mechanisms were still underway in an attempt to control inflammation. From the SPM, only RvE1 was detected in plasma, whereas MaR2, RvE1, RvE2 and RvE4 were detected in the uterine fluid, indicating their local action at low concentrations. In conclusion, this foundational study is consistent with a role of SPM in postpartum uterine inflammation resolution mechanisms.