Gross and Histologic Assessment of a New Platform for Urinary Toxicological Testing

Introduction: We use mice to study male urinary dysfunction, including the role of environmental contaminants. However, little baseline data of mouse lower urinary tract exists. The goal of this study is to determine the impact of sex, androgens, and prostate size on gross morphology of mouse urinary tract and internal anatomy of the urethra. Methods: Androgens and prostate size were manipulated through exogenous testosterone supplementation, high dose finasteride (5-alpha-reductase inhibitor), and, in males, surgical castration and genetic ablation of prostatic luminal cells. We serially sectioned a control male mouse urethra in the transverse plane for H&E assessment. We performed IHC on a transverse section in our region of interest in order to quantify internal and external prostate gland characteristics. We also plan to compare the internal structure of the female urethra. Experimental Design: All mice were on a C57Bl6/J background and collected at 9-weeks-of-age (n=4-11 per group). Results: Our serial H&E sections of male mouse urethra created a complete map the internal structure of the prostatic urethra from bladder neck to pelvic urethra and allowed us to identify regions for further assessment. We have completed staining of various hormone and prostate size manipulations in male mice and are beginning quantitative analysis. Conclusions: Different prostate size and androgen manipulations (castration vs finasteride vs testosterone) have different impacts on the external and internal anatomy of the lower urinary tract. Impact: We provide key information for researchers using mouse models to study urinary function and established new urology-focused endpoints for toxicological testing.