How can blood calcium concentration and oral supplementation affect uterine health in dairy cows?

A series of experiments was carried out to study the effects of blood calcium (Ca) concentration on the occurrence of subclinical endometritis (SE) in dairy cattle. In Experiment 1, serum Ca level of 26 cows in the first 24 h after calving was evaluated and correlated with the incidence of SE between 34 and 40 days postpartum. The polymorphonuclear leukocytes (PMN) count was affected by Ca blood concentration in the first 24 h postpartum (P ≤ 0.01). In Experiment 2, a total of 47 cows retrospectively classified as normocalcemic (Ca ≥8.5 mg/dL) or hypocalcemic (Ca <8.5 mg/dL) were randomly assigned to receive or not oral Ca formate at 6 and 30 h postpartum, and the effects of supplementation on SE incidence were evaluated. The treatment with Ca formate, regardless of Ca concentration, reduced PMN count and incidence of SE between 34 and 40 days postpartum (P < 0.05). For each increase of 1 mg/dL in blood Ca, SE incidence decreased by 22 %. In Experiment 3, five multiparous Holstein cows were enrolled in a 2x2 crossover model and assigned to 1 of 2 treatments: normocalcemic (Control) or induced subclinical hypocalcemia (iSCH) group. The sequence of treatments for a given cow was either Control-iSCH or iSCH-Control, followed by a 3-week washout period. The iSCH group received an intravenous infusion of 5 % disodium tetraacetic ethylenediamine Na2EDTA at 500 mL/h for 45 min, while the Control group received 0.9 % NaCl. Levels of ionized Ca (iCa), total Ca (tCa) and Mg were determined immediately before the treatments (M0), at 15 (M1), 45 min (M2, end of infusions) and 3 h after the end of treatments (M3). Furthermore, glucose, insulin, NEFA and BHB levels were determined at M3. Immediately after the end of the infusions (M2), all animals received an intrauterine challenge with 300 μg of LPS and, after 3 h (M3), an endometrial biopsy was performed to determine the expression of IL-6, CXCL8 and TNF and gene expression of glucose-insulin receptors and insulin-related genes. Subclinical hypocalcemia was effectively induced; however, the expression of IL-6, CXCL8 and TNF in the endometrium did not differ between groups within 3 h after intrauterine LPS challenge. The iSCH group presented a significant reduction in serum BHB levels compared to the Control group, but there were no differences in serum glucose, insulin, NEFA and in the endometrial expression of the INSR, IRS1, IGF1, SLC2A1, and SLC2A3 genes. In conclusion, PMN infiltration and the incidence of SE from 34 to 40 days postpartum is related to blood Ca immediately after calving. Ca supplementation with Ca formate decreases the number of PMNs in the endometrium, reducing SE incidence. In addition, transient iSCH does not cause immediate significant changes in the endometrial expression of key inflammatory cytokines and does not adversely affect the insulin signaling pathway in the uterus within 3 h following an intrauterine challenge with LPS. This study provides valuable insights on the role of blood calcium and oral calcium supplementation during the immediate postpartum period on uterine health and the metabolic and immunological effects of transient induced subclinical hypocalcemia in dairy cows.