Experimental models for subclinical hypocalcemia and endometritis induction in cattle: a literature review

Serum calcium fluctuations are common during the peripartum period of dairy cattle and several studies have attempted to demonstrate the impact of decreased blood calcium (Ca) on subclinical endometritis; however, the highly dynamic and complex nature of the peripartum period in dairy cows may impair the establishment of the cause-and-effect relationship. The objective of this review is to compile information regarding hypocalcemia and subclinical endometritis and their relationship, as well as the available in vivo and in vitro study models that artificially induce subclinical states of hypocalcemia and endometritis in cows that are not in peripartum period. Regarding hypocalcemia, several studies have demonstrated the effectiveness and safety of protocols using Ca chelators such as ethylenediaminetetraacetic acid (EDTA) or ethylene glycol tetraacetic acid (EGTA) in vivo. The induced transitory hypocalcemia impaired feed intake, rumination and neutrophilic phagocytic and oxidative burst response. However, the effects on uterine environment remain poorly explored. Although these experimental models allow the understanding of the effects of hypocalcemia alone, without the peripartum metabolic and hormonal variations, the effects are likely underestimated because dairy cows may experience hypocalcemia for much longer periods. For studying bovine endometritis, the main experimental in vivo model is the intrauterine infusion of pathogenic bacteria or their components (lipopolysaccharide - LPS), which induce endometrial inflammation, even causing long-term negative effects. Several in vitro and ex vivo models have also been developed, which are mainly indicated to investigate the mechanisms underlying endometrial inflammation in cattle because there is no interaction with other tissues, organs and systems, as would occur in vivo. In conclusion, current models still face limitations and, therefore, future efforts to the development and refinement of in vivo and in vitro experimental models are necessary.