Development of male and female models of long urethral strictures in swine

Background: Preclinical animal models which mimic the dimensions of long urethral strictures (>2 cm in length) encountered in the clinic are necessary to evaluate prospective graft designs for urethroplasty. The purpose of this study was to develop both male and female porcine models of long urethral strictures (similar to 4 cm in length) and characterize histological and functional outcomes of iatrogenic stricture formation between genders. Methods: Focal, partial thickness urethral injuries were created over 5-6 cm long segments in male and female swine (N = 4 per gender) via electrocoagulation and the degree of stricture formation was monitored for up to 6 weeks by urethroscopy and retrograde urethrography. Animals were sacrificed following stricture confirmation and histological, immunohistochemical, and histomorphometric analyses were performed on strictured and uninjured control urethral segments to profile wound healing responses. Results: Urethral stricture formation was detected in all female swine by 2 weeks and 100 % of male swine at 3.2 +/- 1.8 weeks, post-operatively. The mean length of urethral strictures in both male and female swine was similar to 4 cm. Substantial variations in the degree of stricture severity between sexes were observed with males exhibiting significant urethral stenosis and loss of alpha-smooth muscle actin+ smooth muscle bundles in comparison to controls, while females primarily displayed defects in pan-cytokeratin+ epithelia as well as functional urethral obstruction. Conclusions: Electrocoagulation injury is sufficient to produce long urethral strictures in male and female swine and the degree of stricture severity and nature of urethral obstruction was observed to be dependent on gender.