PD23-02 LONG LASTING IMPACT OF EARLY LIFE VOIDING DYSFUNCTION ON LOWER URINARY TRACT FUNCTION IN A MURINE MODEL

Abstract

You have accessJournal of UrologyCME1 Apr 2023PD23-02 LONG LASTING IMPACT OF EARLY LIFE VOIDING DYSFUNCTION ON LOWER URINARY TRACT FUNCTION IN A MURINE MODEL Nao Iguchi, Duncan Wilcox, Anna Malykhina, and Dan Wood Nao IguchiNao Iguchi More articles by this author , Duncan WilcoxDuncan Wilcox More articles by this author , Anna MalykhinaAnna Malykhina More articles by this author , and Dan WoodDan Wood More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003296.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The aim of this study was to investigate long term outcome of voiding dysfunction during early childhood in mice. Despite the association between childhood dysfunctional voiding and lifelong bladder dysfunction with or without renal failure, the underlying mechanism remains poorly understood. Neonatal maternal separation (NMS) disturbs the physiological voiding cycle in mouse pups; which is normally maintained by perigenital-bladder reflex via their mother licking the perineum. METHODS: Newborn mouse pups were divided into control and NMS groups after birth. NMS pups were removed from their dam and housed individually (6 h/day) from postnatal day 2 to 14. Pups in the control group stayed with their dam all the time. Long-term effects of early life voiding dysfunction on LUT were assessed in vivo by void spot assay at 3-, 6-, and 12-months old, and in vitro by detrusor contractility studies using bladder strips at 12 months old. RESULTS: NMS male mice showed urinary frequency with small voids by 1.6 to 2.2-fold through middle-age (12mo≈40yr-old human) (Figure 1). There was a trend towards increased number of small voids in females experienced NMS compared to the control group, however, the change was statistically insignificant (1.2 to 1.5-fold, p>0.05). A significant increase in nerve-mediated (electric field stimulation, EFS) and purinergic agonist (ATP)-induced detrusor contractility was observed in NMS group compared to the control group (1.4-fold, p<0.05). There were no changes in contractility in response to carbachol or substance-P (SP), however, preincubation of the bladder strips with SP induced a 1.6-fold larger decrease in nerve-mediated contractility (TmaxEFS) in NMS group than that in the control group (p<0.005, Figure 2). CONCLUSIONS: Our results provide evidence that the early life disturbance of normal voiding cycle had prolonged impacts on LUT function accompanied with an enhanced involvement of purinergic and peptidergic neurons/signaling in detrusor contractility in later of life. Source of Funding: Ponzio Family Endowment Fund (D.W.) © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e670 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nao Iguchi More articles by this author Duncan Wilcox More articles by this author Anna Malykhina More articles by this author Dan Wood More articles by this author Expand All Advertisement PDF downloadLoading ...