Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment

Abstract

Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of lower urinary tract symptoms. Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomic, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multiparameter “baseline” of voiding function in intact male and female 9-wk-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrated male mice, male (and female) mice treated with the steroid 5α-reductase inhibitor finasteride, or male mice harboring alleles ( Pbsn4cre/+; R26RDta/+) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female mice) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male mice). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.

Insight and Resources From a Study of the “Impact of Sex, Androgens, and Prostate Size on C57BL/6J Mouse Urinary Physiology

“…15 We also found that these baseline difference in males and females are likely due to testosterone and not anatomical differences, such as presence of prostate. 15…”

“…Also using VSA and cystometry, we have established baseline urinary characteristics of male and female C57BL/6J mice. 15 We found female mice start to urinate at a higher bladder pressure, reach a higher maximal bladder pressure during voiding, urinate quicker, and urinate a greater volume than male mice. 15 We also found that these baseline difference in males and females are likely due to testosterone and not anatomical differences, such as presence of prostate.…”

“…We recently used VSA to assess urinary function at 6, 7, 8, 9, 10, 12, and 14 weeks of age in intact male C57BL/6J mice. 15 All measured end points changed with age. 15 We believe these are background age-related changes in healthy adult male mice and are potentially behavioral but likely not pathological.…”

“…15 All measured end points changed with age. 15 We believe these are background age-related changes in healthy adult male mice and are potentially behavioral but likely not pathological. Therefore, as with other assays, it is important to consider magnitude of change and concurrent findings when determining whether a statistical change in a VSA parameter is indicative of disease.…”

“…14 Normal values for male and female 9-week-old C57BL/6J mice are available in our recent publication. 15 A description of how to set up VSA, analyze papers, and the individual end points is included in the Void Whizzard user guide. Void Whizzard is not able to account for spots within spots; however, it is able to use algorithms to separate overlapping spots and results in highly reproducible measures with reduced interuser variability.…”