Testosterone Modifies Alterations to Detrusor Muscle after Partial Bladder Outlet Obstruction in Juvenile Mice

Area of Science:

• Urology
• Developmental Biology
• Andrology

Background:

• Posterior urethral valves (PUV) cause lower urinary tract symptoms in adolescent boys, often linked to growth-related urine output changes.
• Current treatment options for PUV complications are limited.
• A new hypothesis suggests elevated androgens during puberty may contribute to bladder dysfunction at a cellular level.

Purpose of the Study:

• To investigate the role of testosterone in bladder detrusor muscle changes following partial bladder outlet obstruction (PO) in a mouse model.
• To determine if testosterone exacerbates fibrotic changes in obstructed bladders.

Main Methods:

• A partial bladder outlet obstruction (PO) model was created in juvenile male mice.
• Groups included: PO (obstructed), CPO (castrated and obstructed), and CPOT (castrated, obstructed, and testosterone-treated).
• Bladder function (voided volumes), bladder weight, and histology (collagen to smooth muscle ratio) were assessed.

Main Results:

• Obstructed mice (PO) showed reduced voided volumes and increased bladder-to-body weight ratios compared to sham mice.
• Castration (CPO) improved voided volumes and reduced bladder hypertrophy, indicating testosterone's detrimental effect.
• Testosterone restoration (CPOT) reversed these improvements, leading to persistent low voided volumes and increased bladder fibrosis (higher collagen/smooth muscle ratio).

Conclusions:

• Testosterone plays a significant role in promoting bladder fibrosis after obstruction in male mice.
• These findings suggest that androgens may contribute to cellular changes in the bladder of boys with PUV.
• This research opens avenues for novel therapeutic strategies targeting testosterone-mediated pathways to treat bladder fibrosis.