Metritis and the uterine disease microbiome are associated with long-term changes in the endometrium of dairy cows†.

Cows with metritis (uterine disease) during the first 1 to 2 wk postpartum have lower pregnancy rates when inseminated later postpartum (typically >10 wk). We hypothesized that metritis and the disease-associated uterine microbiome have a long-term effect on endometrial gene expression. Changes in gene expression may inform a mechanism through which disease lowers pregnancy rates. A total of 20 cows were enrolled at 1 to 2 wk postpartum to either metritis (clinical disease; n = 10) or healthy (control; n = 10) groups and randomly assigned to be slaughtered at approximately 80 d and 165 d postpartum (mid-lactation). The microbiome of the reproductive tract was sampled to confirm the presence of pathogens that are typical of metritis. In addition to the original clinical diagnosis, study cows were retrospectively assigned to uterine-disease and control groups based on the composition of their microbiome. There was no effect of early postpartum uterine disease on the uterine microbiome at mid-lactation (time of slaughter). Nonetheless, early postpartum metritis and the disease microbiome were associated with a large number of differentially-expressed genes at mid-lactation primarily in the caruncular compared with the inter-caruncular endometrium. Gene enrichment analysis identified oxidative phosphorylation as the primary pathway increased in caruncular endometrium of diseased cows whereas growth factor signaling pathways were reduced. The current study demonstrated that metritis and a uterine disease microbiome leave a sustained imprint on gene expression in the caruncular endometrium that may explain lower fertility in cows with postpartum uterine disease.

Testing the Induction of Metritis in Healthy Postpartum Primiparous Cows Challenged with a Cocktail of Bacteria.

Metritis is a postpartum uterine disease with greater incidence in primiparous than in multiparous cows. In primiparous cows, the impact on production and health is lessened, presumably due to a superior immune response. Here, we tested whether an in vivo model of clinical metritis induction developed for postpartum multiparous Holstein cows would produce similar results in primiparous cows. Thirty-six cows were randomly assigned to one of three groups and received intrauterine infusion within 24 h of parturition. The controls were infused with sterile saline; the low-dose group received a bacterial cocktail containing 103 cfu of Escherichia coli, Trueperella pyogenes, and Fusobacterium necrophorum; and the high-dose group were infused with 106 cfu of the same cocktail. Production, health traits, and the vaginal discharge culture were assessed daily, from enrollment until 14 d in milk. Clinical metritis occurred in 64% of high-dose cows, 33% of the controls, and 42% of low-dose cows, with no significant difference of incidence between groups. However, when accounting by time, high-dose cows had a 2.7 times greater hazard of metritis compared with the controls. The bacterial challenge affected milk production and dry matter intake tended to decrease. In the high-dose group, a greater growth of F. necrophorum in the selective medium was also observed, suggesting an association with metritis. Therefore, this study suggests intrauterine inoculation with 106 cfu of this bacterial cocktail elicits physical and clinical outcomes consistent with clinical metritis.