Mp59-18 Unraveling the Urinary Incontinence Puzzle: Exploring Female Urethral Changes With Aging as a Central Element in Urinary Incontinence

You have accessJournal of UrologyUrodynamics/Lower Urinary Tract Dysfunction/Female Pelvic Medicine: Basic Research & Pathophysiology (MP59)1 May 2024MP59-18 UNRAVELING THE URINARY INCONTINENCE PUZZLE: EXPLORING FEMALE URETHRAL CHANGES WITH AGING AS A CENTRAL ELEMENT IN URINARY INCONTINENCE Zhina Sadeghi, Yi Xi Wu, Amberly Vu, John DeLancey, and Xiaolin Zi Zhina SadeghiZhina Sadeghi , Yi Xi WuYi Xi Wu , Amberly VuAmberly Vu , John DeLanceyJohn DeLancey , and Xiaolin ZiXiaolin Zi View All Author Informationhttps://doi.org/10.1097/01.JU.0001009476.18935.3b.18AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The decline of urethral function with advancing age plays a key role in urinary incontinence in women. However, none of the current urinary incontinence treatments address the declining urethral function with aging, and the mechanisms by which aging impacts urethra physiology remain little known or explored. Here, the functional, morphometric, and global gene expression of urethral tissues between young and aged female mice urethras have been compared. METHODS: In this study, bladder leak point pressure (LPP) was measured in young and aged C57BL/6 female mice. Masson's Trichrome staining and Vernhoeff-Van Giesen's staining were performed using sectioning of paraffin-embedded mid-urethras of all mice. Vectorized scale-Invariant Pattern Recognition (VIPR) was used to identify striated muscle (StM), extracellular matrix and connective tissue, and elastin components of the urethral wall. Total RNA was extracted from young and aged mouse urethral tissues, followed by next-generation sequencing. Bioinformatic analysis of the RNA-seq data was performed utilizing Qiagen CLC BenchWork. One-step real-time reverse transcription-quantitative polymerase chain reactions (RT-qPCR) were performed with targeted genes to validate the gene differentially expressed between young and aged urethral tissues. RESULTS: The aged female mice had 26.5% lower LPP than younger mice. VIPR analysis of the relative abundance of different tissue components revealed that the mid-urethra of old female mice contains less striated muscle, more extracellular matrix/fibrosis, and a diminished elastin fibers ratio compared to young mice. Gene expression profiling analysis (bulk RNA-seq of the whole urethra) showed 1544 differentially expressed genes comparing aged and young mice. Gene Set Enrichment Analysis (GSEA) showed Immune response and muscle-related (striated and smooth) pathways were enriched. In contrast, keratinization, skin development, and cell differentiation pathways were significantly down-regulated in aged urethral tissues compared to young. CONCLUSIONS: Functional LPP measurement and morphometric analysis of the aged female mice is qualitatively similar to elderly human urethra. These results suggest that molecular pathways (i.e., ACVR1/FST signaling and CTGF/TGF-β signaling) leading to a decreased striated muscle mass and an increase in fibrous extracellular matrix in the process of aging deserve further investigation for their roles in the declined urethral function. Source of Funding: This work was supported by departmental funding provided to Dr. Zhina Sadeghi, by the Department of Urology at the University of California, Irvine. Dr. DeLancey and Dr. Balis had their effort supported by RC2 DK122379, and NIH.NIAMS R01NS120060 grant (to S.A.V.) © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e964 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Zhina Sadeghi More articles by this author Yi Xi Wu More articles by this author Amberly Vu More articles by this author John DeLancey More articles by this author Xiaolin Zi More articles by this author Expand All Advertisement PDF downloadLoading ...