The Role of Vaginal Smooth Muscle in the Pathogenesis of Pelvic Organ Prolapse

Pelvic organ prolapse (POP) is a life changing condition affecting over 50% of women aged 50 and older. Women with POP typically suffer from sexual, defecatory and urinary dysfunction, resulting from the decent of their unsupported pelvic organs into the vaginal canal. Over one billion dollars in annual costs are associated with surgery to repair POP. In general, surgical repair strategies merely provide an anatomical repair and fail to address the underlying cause of POP, thus increasing the risk of reoccurrence and complications. Vaginal birth injury (VaBI) has been identified as a major risk factor for POP, and as such, provides an opportunity to better understand how POP develops, in order to provide alternate remedies. To date, the exact mechanism by which vaginal delivery leads to POP remains elusive, as the time lapse between childbirth and POP symptoms (usually 20-30 years) creates multiple confounders that limit the ability to prove causality. Therefore, the goal of this thesis work was to utilize controlled animal models to assess the impact of VaBI on vaginal smooth muscle (VaSM), as a possible mechanism of VaBI in the pathogenesis of POP. In addition, we wish to examine the impact of current surgical mesh repair on VaSM functional outcomes. Specially, this work 1) investigated the impact of a simulated vaginal birth injury on VaSM 2) characterized the impact of a potential loss of smooth muscle function on vaginal biaxial mechanics, and 3) evaluated the ability of surgical mesh, designed to restore the unsupported organs to their anatomical position, on VaSM function. Our findings indicate that vaginal birth injury can cause non-recoverable loss in Vim function, and that a loss of function alters vaginal mechanics, with the potential to compromise support of the pelvic organs. Additionally, the results showed that surgically implanted meshes have mechanical and textile properties that further promote a loss of VaSM function. Ultimately, we hope that these findings motivate the need for more measures to prevent VaSM injury during delivery, and perhaps serve as a guide for the design of de novo meshes aiming to improve VaSM function