1384 THE ROLE OF SIMULATED HUMAN CHILDBIRTH INJURIES IN A LYSYL OXIDASE LIKE-1 KNOCKOUT MOUSE MODEL OF PELVIC ORGAN PROLAPSE

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Pelvic Prolapse1 Apr 20101384 THE ROLE OF SIMULATED HUMAN CHILDBIRTH INJURIES IN A LYSYL OXIDASE LIKE-1 KNOCKOUT MOUSE MODEL OF PELVIC ORGAN PROLAPSE Andrew Lenis, Bruce Kinley, Dan Li Lin, and Margot Damaser Andrew LenisAndrew Lenis More articles by this author , Bruce KinleyBruce Kinley More articles by this author , Dan Li LinDan Li Lin More articles by this author , and Margot DamaserMargot Damaser More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.1034AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pelvic organ prolapse (POP) is one of several female pelvic floor disorders, a group of debilitating and poorly understood conditions that may affect up to half of all women in the U.S. No animal besides human routinely develops POP. Dysfunctional elastin homeostasis, in part regulated by the enzyme lysyl oxidase like-1 (LOXL1), has been implicated in the pathophysiology of POP in humans. LOXL1 knockout (KO) mice display anatomical changes similar to those in POP after delivery of mouse pups. We hypothesized that simulated human childbirth injury by vaginal distension (VD) in LOXL1 KO mice would increase the incidence of POP compared to vaginal delivery or Caesarean delivery of pups. METHODS Age-matched, nulliparous LOXL1 KO mice were randomized into 6 groups and allowed to breed at 6 weeks old. Two groups were delivered by Caesarean section; two groups were allowed to deliver vaginally; and two groups of nulliparous mice were used as controls. One group from each of these delivery modes underwent VD. The other group underwent sham VD. Weekly assessment of POP using the validated Mouse Pelvic Organ Prolapse Quantification (MOPQ) staging system was used to determine timing and staging of POP for 12 consecutive weeks after injury. RESULTS Twelve mice delivered vaginally, 13 mice delivered via Caesarean section, and 4 nulliparous mice were used as controls. Six of the 12 mice that delivered vaginally underwent VD and 6 underwent sham VD. Nine of the 13 mice that delivered via Caesarean section underwent VD and 4 underwent sham VD. Delivery groups took significantly less time to develop POP (3.7 ± 0.8 weeks) than Caesarean section groups (5.9 ± 0.7 weeks; Wilcoxon, p=0.04). Time to POP after VD was not significantly different than after sham VD, regardless of delivery mode. Nulliparous mice rarely develop POP, even after VD. CONCLUSIONS Our results indicate that simulated human birth injury does not decrease the time to POP in LOXL1 KO mice, suggesting that hormonal changes and aspects of delivery other than direct trauma play an important role in POP development. The mechanism of these findings will be investigated in future studies. Cleveland, OH© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e535 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Lenis More articles by this author Bruce Kinley More articles by this author Dan Li Lin More articles by this author Margot Damaser More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...