A novel in vivo model of ureteral fibrosis induced by calcium oxalate beads in C57BL/6J mice

Abstract

Abstract The global incidence of ureteroliths in humans is increasing, particularly posing a problem in developed countries. The most common stone type is calcium oxalate, which is associated with a high recurrence rate. In veterinary medicine, stones are the most common cause of ureteral obstruction in cats, accounting for 72–87% of cases. In cats, stones cause irreversible ureteral damage, necessitating stone treatment as well as ureteral therapy. However, the mechanisms underlying the ureteral damage caused by stones remain unclear. Therefore, this study aimed to create a mouse model suitable for studying the ureteral fibrosis caused by oxalate stones by artificially embedding calcium oxalate in the ureter. Pathological tissue analysis was used to compare normal ureters without ligation and ureters with sham or oxalate bead implantation. The ureters of the sham and oxalate bead groups showed granulation tissue formation, transitional epithelium exfoliation, and densely packed connective tissue in the proprietary and muscle layer regions. Particularly in the oxalate bead group, infiltration of degenerated neutrophils, presence of foreign body giant cells, and hyperplasia of the transitional epithelium were observed. The proportion of fibrosis was higher in the oxalate group than in the sham group. Overall, this mouse model created using oxalate bead implantation has the potential to efficiently induce ureteral obstruction. This mouse model is expected to be used for elucidating the molecular mechanisms of ureteral fibrosis and evaluating therapeutic drugs in future.