Login to Access Video or Poster Abstract: MP45-03
Sources of Funding: UCSD Academic Senate

Introduction

Pathophysiology/ molecular mechanisms of age-related penile hemodynamic impairment are unclear. Previous studies suggest age-related increase in tissue fibrosis in several organs including male genital tissues leading to impaired hemodynamics and male erectile dysfunction (ED). We tested the hypothesis that increased penile/ perineal (ischiocavernosus; ICM) muscle fibrosis during advanced aging is mediated by a novel fibrogenic cascade involving GIV/girdin and Wnt signaling pathways. A clear understanding of these molecular mechanisms involved in penile fibrosis would enable development of optimal strategies to treat ED.

Methods

Young (n=3; 9 months) and old (n=6; 36 months) New Zealand White rabbits were anesthetized and penile tissue microcirculatory blood perfusion (perfusion units- PU) was measured using a novel PeriCam PSI system. Blood perfusion measurements were made before and after an intracavernosal injection of vasoactive agent- PGE1 (50 ng). Penile (corpus cavernosum) and ICM tissues were harvested and paraffin sections of these tissues were subjected to: (1) trichrome staining (marker of fibrosis) followed by image analysis for evaluation of fibrosis and (2) immunostaining for specific markers of fibrosis: 1. [beta]-catenin (central mediator of Wnt pathway) and 2. GIV/girdin.

Results

Representative tracings of time-course of penile blood perfusion measurements in response to intracavernosal PGE1 as well as age-related penile perfusion changes in young and old rabbits are shown in figure A. Photomicrographs of showing trichrome as well as immunostaining for fibrosis markers (GIV and [beta]-catenin) are depicted in Fig B. A significant impairment in penile perfusion (Fig A) and increased fibrosis of penile/ICM tissues was observed in old rabbits (Fig B) when compared to the young animals. Immunostaining studies revealed positive labelling for both GIV and and [beta]-catenin and increased immunoreactivity in the tissues from old rabbits (Fig B).

Conclusions

Our findings suggest age-related increase in penile/ perineal muscle (ICM) fibrosis may contribute to increased incidence of ED in older men. Targeting GIV-Wnt pathways may be beneficial in preventing age-related ED for the aging population

Funding

UCSD Academic Senate