Validation of Animal Model of Pelvic Radiation Induced Female Sexual Dysfunction and Cystitis [35D

Abstract

INTRODUCTION: Women receiving radiation therapy (RT) for cervical and endometrial cancers experience injury and fibrosis to surrounding healthy tissues leading to genitourinary dysfunction, specifically vaginal atrophy, dyspareunia and radiation cystitis. METHODS: Adult female Sprague-Dawley rats were separated into three groups (n=7-8/group): control, 4-week RT, and 9-week RT. RT rats received a single 20Gy dose of cervical x-ray irradiation. In vivo, pelvic nerve electric field stimulated (EFS) increases in vaginal blood flow were measured using a laser Doppler probe. Ex vivo tissue bath experiments assessed vaginal adrenergic and cholinergic contractions. Bladder cholinergic contractions were measured in the presence or absence of muscarinic inhibition. Internal and external urethral sphincter contractions to cholinergic agonists and caffeine were measured. EFS neurogenic contractions were evaluated in all tissues. Experiments were conducted in accordance with the East Carolina University Institutional Animal Care and Use Committee. RESULTS: Pelvic RT caused a decrease in vaginal blood flow and less cholinergic vaginal contraction 4-weeks post-RT. Following 9-weeks RT, vaginal blood flow normalized; however, adrenergic-mediated vaginal contraction remained elevated. In both RT groups, EFS neurogenic-mediated bladder contractions were reduced. No changes were observed in internal urethral sphincter contractility. In contrast, external urethral sphincter contractions to EFS and caffeine were elevated at 4 and 9-weeks post-RT. CONCLUSION: This pelvic RT model demonstrated impaired sexual arousal and increased vaginal contractility. Similar to previous RT studies, the bladder developed decreased neurogenic contractions; a symptom of radiation cystitis. Using our female pelvic RT model, we can begin to understand the pathophysiology of RT-induced sexual dysfunction and cystitis.