2137 INJURY RELATED STEM CELL HOMING CYTOKINES IN LYSYL OXIDASE LIKE-1 KNOCKOUT MICE: A PELVIC ORGAN PROLAPSE MODEL

Abstract

You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Pelvic Prolapse1 Apr 20122137 INJURY RELATED STEM CELL HOMING CYTOKINES IN LYSYL OXIDASE LIKE-1 KNOCKOUT MICE: A PELVIC ORGAN PROLAPSE MODEL Bruna M. Couri, Andrew T. Lenis, Bruce Kinley, Brian M. Balog, Mei Kuang, and Margot S. Damaser Bruna M. CouriBruna M. Couri Cleveland, OH More articles by this author , Andrew T. LenisAndrew T. Lenis Cleveland, OH More articles by this author , Bruce KinleyBruce Kinley Cleveland, OH More articles by this author , Brian M. BalogBrian M. Balog Cleveland, OH More articles by this author , Mei KuangMei Kuang Cleveland, OH More articles by this author , and Margot S. DamaserMargot S. Damaser Cleveland, OH More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2308AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Pregnancy and childbirth are significant risk factors for pelvic organ prolapse (POP). Animal models have shown upregulation of injury-related stem cell homing cytokines after simulated human childbirth, including monocyte chemotactic protein-3 (MCP-3) and stromal derived factor-1 (SDF-1). Our aim was to assess upregulation of these cytokines to identify pregnancy and delivery contributions to pelvic tissue injury in lysyl oxidase like-1 knockout (LOXL1 KO) mice, a well-characterized model of POP. METHODS LOXL1 KO mice were bred at 8 weeks old. Urethra, vagina, and bladder were harvested under isoflurane anesthesia 15 minutes (15'), 1 or 12 hours (hr) after vaginal delivery or C-section. Sham C-section and nulliparous female mice constituted controls. RT-PCR was used to evaluate the relative expression of MCP-3 and SDF-1 in each organ, normalized to 18S. RESULTS 15' after vaginal delivery MCP-3 in the urethra was increased 400-fold and decreased over the next 12hr, yet remained significantly elevated compared to controls (p<0.001). Similar trends were seen in the C-section group. In the vagina, MCP-3 was overexpressed 30-fold 15' after vaginal delivery compared to controls (p<0.001); continued to be overexpressed 1hr after delivery, and was significantly underexpressed after 12hr (p=0.01). MCP-3 was significantly overexpressed 15' after C-section in the vagina (p<0.001) and normalized after 1hr. MCP-3 was significantly overexpressed in the bladder 70-110 fold in all groups 15' after delivery (p<0.05). Only the C-section and sham C-section groups remained significantly elevated compared to controls at 1hr. SDF-1 was not significantly different from controls at any time point in the urethra or vagina. In the bladder, SDF-1 was upregulated 3-5 fold in all groups 15' after delivery. SDF-1 was significantly downregulated in the bladder in all groups 12 hr after delivery. CONCLUSIONS MCP-3 is significantly overexpressed in the pelvic organs of LOXL1 KO mice soon after delivery. This over-expression is not entirely eliminated by C-section, implicating pregnancy-associated factors. Time to normalization of this upregulation appears to be both organ and delivery mode dependent. While SDF-1 appears to play a role in bladder response to injury, its role is less important in the urethra and the vagina. These cytokines may allow systemically delivered stem cells to home to critical areas of injury to facilitate post-partum repair and prevent or attenuate the development of POP. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e863 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bruna M. Couri Cleveland, OH More articles by this author Andrew T. Lenis Cleveland, OH More articles by this author Bruce Kinley Cleveland, OH More articles by this author Brian M. Balog Cleveland, OH More articles by this author Mei Kuang Cleveland, OH More articles by this author Margot S. Damaser Cleveland, OH More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...