Pelvic floor disorders (PFD) include pelvic organ prolapse (POP), urinary incontinence, and fecal incontinence. Their impact on women is significant, causing pelvic pain, sexual dysfunction, social isolation, depression, and poor body image. PFD etiology is multifactorial and complex, with vaginal delivery identified as the leading risk factor for its development. The critical barrier that limits progress in identifying the precie cause of PFD is our lack of understanding of fundamental mechanisms that lead to pelvic floor dysfunction. Imaging and modeling studies have provided ample evidence that skeletal muscles are substantial contributors to pelvic floor support and are deleteriously affected by vaginal birt, but these reports have not causally linked vaginal birth, pelvic floor muscles'injury, and PFD in a mechanistic fashion. This significant knowledge gap makes it difficult to cultivate effective preventive measures and/or treatments for PFD. To define a potential mechanism that links pelvic floor striated muscle function and PFD, muscle architecture and the properties of its extracellular matrix (ECM) will be quantified. This will allow us to elucidate the structure-functin relationships in these muscles. In the field of orthopedics, significant advances in the treatment of muscular dysfunction became possible once precise muscles'structure, physiology and pathophysiology were established. An analogous leap forward is essential for progress to be realized in female pelvic medicine. In this proposal, we will define the architecture and intramuscular ECM of pelvic floor muscles from nulliparous and parous female human cadavers in order to understand specifics of these muscles'design and function that allow them to serve a complex dual role: provide support to the pelvic viscera and aid in continence, as well as facilitate urination, defecation, and parturition. We hypothesize that individual pelvic floor muscles'architecture and ECM are differentiated to allow for specialized roles in the pelvic floor Individual pelvic floor muscles are variably but permanently altered by vaginal deliveries, which compromises their function. These changes negatively impact biomechanical properties and contribute to the development of pelvic floor dysfunction later in life. The results of these studis will improve our understanding of events that cause pelvic floor muscles to switch from physiological to pathological remodeling and will have major implications in developing effective strategies for averting or delaying PFD. The interdisciplinary approach used in our research will have a significant impact on these vastly understudied conditions that negatively affect the lives of millions of women world-wide.

Public Health Relevance

Pelvic floor disorders (PFD), which include prolapse (i.e. descent), urinary and fecal incontinence is a common costly condition that negatively impacts the quality of life of millions of women. Pelvic floor muscles play an important role in support of the pelvic organs and get damaged during vaginal birth, which is considered the greatest risk factor for PFD. In this proposal, we use a multi-faceted approach to establish structure and function of the pelvic muscles and to define the destabilizing changes induced by vaginal deliveries in these major constituents of the pelvic floor support.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Small Research Grants (R03)
Project #
Application #
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Meikle, Susan
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Diego
Obstetrics & Gynecology
Schools of Medicine
La Jolla
United States
Zip Code
Stewart, Amanda M; Cook, Mark S; Dyer, Keisha Y et al. (2018) Structure-function relationship of the human external anal sphincter. Int Urogynecol J 29:673-678
Stewart, Amanda M; Cook, Mark S; Esparza, Mary C et al. (2017) Architectural assessment of rhesus macaque pelvic floor muscles: comparison for use as a human model. Int Urogynecol J 28:1527-1535
Cook, Mark S; Bou-Malham, Laura; Esparza, Mary C et al. (2017) Age-related alterations in female obturator internus muscle. Int Urogynecol J 28:729-734
Alperin, Marianna; Cook, Mark; Tuttle, Lori J et al. (2016) Impact of vaginal parity and aging on the architectural design of pelvic floor muscles. Am J Obstet Gynecol 215:312.e1-9
Tuttle, Lori J; Alperin, Marianna; Lieber, Richard L (2014) Post-mortem timing of skeletal muscle biochemical and mechanical degradation. J Biomech 47:1506-9