Arlan Marcus Gustilo-Ashby1, Una Lee, Drina Vurbic, David Sypert, Mei Kuang, Firouz Daneshgari, Matthew D Barber, Margot S Damaser. 1. From the *Center for Urogynecology and Reconstructive Surgery, Obstetrics, Gynecology and Women's Health Institute, Cleveland Clinic, Cleveland, OH; †Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic, Cleveland, OH; ‡Research Service, Department of Veterans Affairs Medical Center, Louis Stokes Cleveland, Cleveland, OH; and §Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
Abstract
OBJECTIVE: : Lysyl oxidase like-1 (LOXL1) knockout mice have abnormal elastic fiber homeostasis and frequently develop pelvic floor dysfunction after pregnancy and delivery. The objective of this study was to test the hypothesis that tissue changes associated with vaginal delivery lead to pelvic floor dysfunction as a result of abnormal elastic fiber homeostasis. METHODS: : Female LOXL1 knockout mice delivered either spontaneously or by cesarean delivery. Mice were assessed weekly for pelvic organ prolapse (POP). At 12 weeks postpartum, lower urinary tract function was assessed by cystometry and leak-point pressure testing. Urethrovaginal cross-sections were analyzed using a histologic grading scale to assess elastin fiber disorganization. RESULTS: : A total of 39 mice delivered by spontaneous vaginal delivery and 36 by cesarean delivery. Twelve weeks after spontaneous vaginal delivery or cesarean delivery, 23 (59%) and 11 (31%) mice had developed POP, respectively. The mean time to develop POP was 7.2 weeks after spontaneous vaginal delivery and 10.5 weeks after cesarean delivery (log rank, P = 0.0008). The Cox proportional hazard ratio was 0.55 (95% confidence interval, 0.38-0.79). Mice with POP had increased frequency of bladder contractions not associated with voiding during cystometry (P = 0.02). POP, but not mode of delivery, was associated with increased elastic fiber disorganization. CONCLUSIONS: : Cesarean delivery delays the development of POP in LOXL1 knockout mice. POP is associated with increased bladder contraction frequency and increased elastic fiber disorganization in the urethra and vagina. The mechanisms underlying these findings warrant further investigation.
OBJECTIVE: : Lysyl oxidase like-1 (LOXL1) knockout mice have abnormal elastic fiber homeostasis and frequently develop pelvic floor dysfunction after pregnancy and delivery. The objective of this study was to test the hypothesis that tissue changes associated with vaginal delivery lead to pelvic floor dysfunction as a result of abnormal elastic fiber homeostasis. METHODS: : Female LOXL1 knockout mice delivered either spontaneously or by cesarean delivery. Mice were assessed weekly for pelvic organ prolapse (POP). At 12 weeks postpartum, lower urinary tract function was assessed by cystometry and leak-point pressure testing. Urethrovaginal cross-sections were analyzed using a histologic grading scale to assess elastin fiber disorganization. RESULTS: : A total of 39 mice delivered by spontaneous vaginal delivery and 36 by cesarean delivery. Twelve weeks after spontaneous vaginal delivery or cesarean delivery, 23 (59%) and 11 (31%) mice had developed POP, respectively. The mean time to develop POP was 7.2 weeks after spontaneous vaginal delivery and 10.5 weeks after cesarean delivery (log rank, P = 0.0008). The Cox proportional hazard ratio was 0.55 (95% confidence interval, 0.38-0.79). Mice with POP had increased frequency of bladder contractions not associated with voiding during cystometry (P = 0.02). POP, but not mode of delivery, was associated with increased elastic fiber disorganization. CONCLUSIONS: : Cesarean delivery delays the development of POP in LOXL1 knockout mice. POP is associated with increased bladder contraction frequency and increased elastic fiber disorganization in the urethra and vagina. The mechanisms underlying these findings warrant further investigation.
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