Session: MP27: Sexual Function/Dysfunction: Basic Research & Pathophysiology
MP27-02: Microarray Analysis of Corpora Cavernosal Tissue from Peyronie’s and Prostatectomy Patients with Erectile Dysfunction in comparison to a Rat Cavernous Nerve Resection Model
Associate Professor University of Illinois at Chicago
Introduction: Prostatectomy patients are at high risk of erectile dysfunction (ED) that is refractory to PDE5 inhibitors. Cavernous nerve (CN) damage causes loss of innervation, smooth muscle apoptosis, and fibrosis, resulting in ED. We performed microarray and pathway analysis to identify mechanisms that are altered with ED, to find new targets for ED treatment. Methods: Corpora cavernosal (CC) tissue was obtained from Peyronie’s (control, n=3) and prostatectomy (control, n=3) patients undergoing prosthesis implant to treat ED. For our rat CN injury model, Sprague Dawley rats underwent bilateral CN resection (n=5) or sham surgery (controls, n=5) and C.C. tissue was harvested 2 days post surgery. RNA was extracted from CC tissue using TRIzol, DNase treated, and purified with Qiagen mini kit. Microarray analysis (HG 2.0 ST, RU34), and pathway analysis was performed (ShinyGO, WebGestalt. Ingenuity). A 2-fold change was used as threshold for differentially expressed genes (DEGs). FDR <0.05 was considered significant for enrichment terms. Results: There were 197 DEGs in CC from prostatectomy patients. 112 of the 197 DEGs were non-protein-coding genes. The overall changed expression of these non-protein-coding genes expected to favor a reduction in cell growth compared with Peyronie’s control. In the rat, microarray detected 182 protein coding DEGs. Pathway Analysis identified changes in cell death, stress and cellular development. Examination of the role of individual genes found changes in proliferation and cell death. Conclusions: Prostatectomy patients display alterations in gene expression in their corpora cavernosa that are consistent with decreased growth, likely impacting tissue repair and regenerative processes. Non-protein-coding RNAs may play a crucial role in ED in prostatectomy patients. In the acute rat CN resection model, cell death and proliferation are followed by apoptosis domination. Prostatectomy patient results show penile remodeling continues in patients long after the acute surgical injury to the CN takes place, offering the opportunity for clinical intervention to reverse penile remodeling and improve erectile function. SOURCE OF Funding: NIH/NIDDK DK101536
