2018: IMPACT OF AGE AND CASTRATION ON CANINE PROSTATE COLLAGEN ORGANIZATION


Impact of age and castration on canine prostate collagen organization 
H. Ruetten,a K. Wegner,b S. Colopy,a H. Zhang,d S. Sandhu,a M. Romero,e,f C. Vezinaa,b,g 

aSchool of Veterinary Medicine, bMolecular and Environmental Toxicology Center, dCollege of 
Agriculture & Life Sciences, gCarbone Cancer Center, University of Wisconsin-Madison, Madison WI; 

ePhysiology and Biomedical Engineering, fNephrology and Hypertension, Mayo Clinic College of 
Medicine and Science, Rochester, MN 

 
Prostate-related urinary signs such as incomplete bladder emptying and straining are common in 

older intact male dogs and men. A longstanding paradigm is these symptoms derive from an aging-related 
increase in prostate volume but new evidence suggests additional mechanisms. For example, human 
prostatic collagen content was recently associated with tissue stiffness and urinary retention. The 
implications of which are huge for the veterinary community because treatment of fibrosis would not 
impact fertility like current alpha reductase inhibitors. The present study tested whether canine prostatic 
collagen increases with advancing age and whether castration reduces prostatic collagen content. We also 
used mice as a tractable model to test whether castration changes baseline urination and whether 
testosterone supplements reverse these changes. The canine study involved prostates obtained at necropsy 
divided into four groups: young (≤3 years) intact, young neutered, old (≥5 years) intact, and old neutered 
(n=9, 4, 4, and 14 respectively). Formalin fixed paraffin embedded prostate sections were stained with 
picrosirius red (PSR), imaged with florescent microscopy, and quantitatively analyzed for collagen fiber 
thickness, length, and density using novel computer software (CT FIRE, developed at LOCI- University 
of Wisconsin-Madison). The C57BL/6J mouse study design involved three groups: sham castrated, 
castrated + placebo implant, castrated + slow release testosterone implant (n=8). Urinary function was 
evaluated by anesthetized cystometry. Transverse canine prostate sections (figure) were characterized by 
four histologically distinct regions: urethral, periurethral, peripheral, and capsule. The prostatic urethra 
harbored a thick band of densely packed collagen. Collagen bundles radiated from the urethra and into the 
periurethral region where they branched before extending into the peripheral region. Collagen fibers in 
the peripheral region changed orientation before networking with the circumferential fibers of the capsule. 
Collagen fibers were denser in periurethral and peripheral regions of neutered male prostates compared to 
intact. Prostatic peripheral region collagen fibers were denser and the capsular collagen fibers thicker in 
old intact male prostates compared to compared to young intact males (p = 0.0251 and 0.0470, 
respectively). In mice, castration reduced void duration and time between voids, and testosterone 
supplementation returned void duration to that of intact but did not alter 
the reduced time between voids. Consistent with our hypothesis, this 
study revealed aging related increases in collagen density in intact males, 
and surprisingly castration was protective against these increases. 
Contrary to our hypothesis, castration resulted in increased glandular 
collagen density. These studies are the first to characterize regional 
collagen organization in the canine prostate and demonstrate the impact 
of castration on mouse voiding behavior. Supported in part by NIH U54 
DK104310 & DK100227.  
 
Keywords: Benign prostatic hyperplasia, collagen, fibrosis, cystometry, 
prostate 

Figure. PSR stained prostate 
section imaged with fluorescent 
microscopy 

Clinical Theriogenology • Volume 10,  Number 3 • September 2018319