Penile Weight and Cell Subtype Specific Changes in a Post-Radical Prostatectomy Model of Erectile Dysfunction

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Abstract
We evaluated neurogenic erectile dysfunction, focusing on the post-radical prostatectomy model. We investigated changes in DNA, protein and apoptotic cells of the rat penis after denervation. Gross morphometry was measured to elucidate the impact of chemical changes. Postpubertal male Sprague-Dawley rats were randomized to bilateral or unilateral cavernous nerve transection, or sham operation. Wet weight, DNA content and protein content were measured. Tissue sections were stained for apoptosis by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling and the apoptotic index was calculated. Dual staining was performed for endothelial and smooth muscle cells to identify apoptotic cells. Penile wet weight was significantly decreased at all time points after bilateral neurotomy (p <0.0005). Unilateral neurotomy allowed much greater preservation of penile weight. DNA content was significantly decreased in bilaterally denervated penes and unchanged in unilaterally operated penes. Protein content was not significantly altered in the bilateral or unilateral cohorts. Bilateral neurotomy induced significant apoptosis, while unilateral surgery caused significantly less apoptosis. Each population had apoptotic clustering just beneath the tunica albuginea, which was mostly smooth muscle cells. These data suggest the importance of neural integrity to maintain penile homeostasis. The loss in penile weight was consistent with the anecdotal experience of many clinicians. Decreased DNA content may have been due to significant levels of apoptosis in smooth muscle cells. Preserved protein content may suggest an increase in extracellular protein, as postulated in corporeal fibrosis. The subtunical population of apoptotic smooth muscle cells revealed a mechanism for veno-occlusive dysfunction observed after radical prostatectomy. These effects were significantly moderated in the unilateral model, reinforcing the critical nature of neural integrity.