Lower urogenital tract anatomical and functional phenotype in lysyl oxidase like-1 knockout mice resembles female pelvic floor dysfunction in humans
- 1 August 2008
- journal article
- Published by American Physiological Society in American Journal of Physiology-Renal Physiology
- Vol. 295 (2), F545-F555
- https://doi.org/10.1152/ajprenal.00063.2008
Abstract
Female pelvic floor dysfunction (FPFD) is a complex group of conditions that include urinary incontinence and pelvic organ prolapse (POP). In humans, elastin homeostasis has been implicated in the pathophysiology of FPFD. Lysyl oxidase-like 1 knockout (LOXL1-KO) mice demonstrate abnormal elastic fiber homeostasis and develop FPFD after parturition. We compared the lower urogenital tract (LUT) anatomy and function in LOXL1-KO mice with and without POP. LUT anatomy was assessed in LOXL1-KO mice over 28 wk. Pelvic visceral anatomy in LOXL1-KO was evaluated with a 7-Tesla magnetic resonance imaging (MRI) scanner. LUT function was assessed using conscious cystometry and leak point pressure (LPP) testing. Quantitative histological analysis of elastic fibers was performed on external urethral sphincter (EUS) cross sections. By 25 wk of age, 50% of parous LOXL1-KO mice developed POP. LOXL1-KO mice with POP had greater variability in the size and location of the bladder on MRI compared with mice without POP. Parity and POP were associated with lower LPP. Elastin clusters were significantly increased in the EUS of LOXL1-KO mice with POP. Because parity triggers POP in LOXL1-KO mice, LOXL1-KO mice with POP have variable internal pelvic anatomy, and both parity and POP are associated with a decrease in LPP, we conclude that LOXL1 LUT anatomical and functional phenotype resembles FPFD in humans. The increase in elastin clusters in the urethra of LOXL1-KO mice with POP suggests that elastin disorganization may lead to functional abnormalities. We conclude that LOXL1 warrants further investigation in the pathphysiology of FPFD.Keywords
This publication has 26 references indexed in Scilit:
- Decreased endopelvic fascia elastin content in uterine prolapseActa Obstetricia et Gynecologica Scandinavica, 2008
- Bladder and urethral function in pelvic organ prolapsed lysyl oxidase like‐1 knockout miceBJU International, 2007
- Clinical and demographic factors associated with valsalva leak point pressure among women undergoing burch bladder neck suspension or autologous rectus fascial sling proceduresNeurourology and Urodynamics, 2007
- Parity, Mode of Delivery, and Pelvic Floor DisordersObstetrics & Gynecology, 2006
- Paper 14: Complete Pelvic Organ Prolapse in Fibulin-5 Knockout Mice: Pregnancy Changes in Elastin and Fibulin-5 Protein in Mouse VaginaJournal of Pelvic Medicine and Surgery, 2005
- Young women with genital prolapse have a low collagen concentrationActa Obstetricia et Gynecologica Scandinavica, 2004
- Elastic fiber homeostasis requires lysyl oxidase–like 1 proteinNature Genetics, 2004
- Elastolytic activity in women with stress urinary incontinence and pelvic organ prolapseNeurourology and Urodynamics, 2004
- Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivoNature, 2002
- Effects of anesthesia on cystometry and leak point pressure of the female ratLife Sciences, 2001