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

Abstract

The National Institutes of Health leveled new focus on sex as a biological variable with the goal of understanding sex-specific differences in health and physiology. We previously published a functional assessment of the impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology (Ruetten H, Wegner KA, Zhang HL, Wang P, Sandhu J, Sandhu S, Mueller B, Wang Z, Macoska J, Peterson RE, Bjorling DE, Ricke WA, Marker PC, Vezina CM. Am J Physiol Renal Physiol 317: F996–F1009, 2019). Here, we measured and compared five characteristics of urethral histology (urethral lumen diameter and area, epithelial cell count, epithelial and rhabdosphincter thickness, epithelial cell area, and total urethral area) in male and female 9-wk-old C57BL/6J mice using hematoxylin and eosin staining. We also compared male mice with castrated male mice, male and female mice treated with the steroid 5α-reductase inhibitor finasteride or testosterone, or male mice harboring alleles ( Pbsn4cre/+; R26RDta/+) that reduce prostate lobe mass. The three methods used to reduce prostate mass (castration, finasteride, and Pbsn4cre/+; R26RDta/+) changed urethral histology, but none feminized male urethral histology (increased urethral epithelial area). Exogenous testosterone caused increased epithelial cell count in intact females but did not masculinize female urethral histology (decrease epithelial area). Our results lay a critical foundation for future studies as we begin to parse out the influence of hormones and cellular morphology on male and female urinary function.

Long‐Term Retention Microbubbles with Three‐Layer Structure for Floating Intravesical Instillation Delivery

“…Then, the mice were administered drugs by intravesical instillation once a week for a total of four times, during which the mice urinated normally since the diameter of urethras of mice (≈2 mm) was greater than the diameter of BSA 20 ‐MBs. [ 27 ] To visually monitor the progress of bladder tumors, noninvasive ultrasound imaging was used to image the tumors throughout the whole treatment process. As shown in Figure 6b, there was a hyperechoic signal in the bladder at day 0, indicating that the orthotopic tumors were successfully constructed, in which the size of tumors could not be identical because of the individual differences between mice.…”

Sex differences in lower urinary tract function in mice with or without spinal cord injury

“…The majority of previous basic research investigations on the mechanisms of LUTD after spinal cord injury (SCI) were predominantly performed using female rodents 3–5 . In addition, there have been no studies of bladder and urethral coordination in male mice although several researchers have suggested that there are sex differences in the urethra, in terms of its function, morphology, and distribution of receptors such as α1‐adrenoceptors and hormonal receptors 6–8 . It has been shown that male and female rats exhibit bursting activity of the external urethral sphincter (EUS) during voiding, which acts as urethral pumping function to help efficient voiding 9–11 .…”

“…[3][4][5] In addition, there have been no studies of bladder and urethral coordination in male mice although several researchers have suggested that there are sex differences in the urethra, in terms of its function, morphology, and distribution of receptors such as α1adrenoceptors and hormonal receptors. [6][7][8] It has been shown that male and female rats exhibit bursting activity of the external urethral sphincter (EUS) during voiding, which acts as urethral pumping function to help efficient voiding. [9][10][11] In contrast, in humans 12 and in female mice, EUS relaxes during voiding, so that voiding occurs during EUSelectromyography (EMG) silent periods in both spinal intact (SI) and SCI conditions, 10 although it is not well clarified whether EUS bursting activity is involved in efficient voiding in male mice.…”