Radiation-Induced Erectile Dysfunction Using Prostate-Confined Modern Radiotherapy in a Rat Model

Abstract

The mechanisms of radiation-induced erectile dysfunction (ED) are unclear, as clinical studies are limited, and previous animal models were based on wide-field irradiation, which does not model current radiotherapy (RT) techniques. To perform functional and morphological analyses of erectile function (EF) utilizing image-guided stereotactic prostate-confined RT in a rat model. Sixty young adult male rats aged 10-12 weeks old were divided into age-matched sham and RT groups. A single 20-Gy fraction to the prostate was delivered to RT animals. Penile bulb, shaft, and testes were excluded from treatment fields. Bioassay and intracavernous pressure (ICP) measurements were conducted at 2, 4, and 9 weeks following RT. Perfusion analysis of the corpora cavernosa (CC) was conducted using Hoechst injected prior to sacrifice. Penile shaft and cavernous nerve (CN) were evaluated by immunohistochemistry. Plasma testosterone level was analyzed using a testosterone enzyme-linked immunosorbent assay (ELISA) assay kit. Irradiated animals demonstrated statistically significant time-dependent functional impairment of EF by bioassay and ICP measurement from 4 weeks. Neuronal nitric oxide synthase (NOS) expression was decreased in CN by 4 weeks. In CC, expression levels of anti-alpha smooth muscle actin and endothelial NOS were significantly decreased at 9 weeks. In penile dorsal vessels, smooth muscle/collagen ratio was significantly decreased at 4 and 9 weeks. Additionally, Hoechst perfusion showed time-dependent decrease in CC of RT animals, whereas CD31 expression was not affected. No toxicities were noted; testosterone levels were similar in both groups. We demonstrated time-dependent ED following image-guided stereotactic RT. Our results imply that reduction of neuronal NOS expression in cavernous nerve could trigger consecutive reduction of smooth muscle content as well as blood perfusion in CC that resulted in corporal veno-occlusive dysfunction. Present study could be a cornerstone to future research that may bring comprehensive scientific understanding of radiation-induced ED.