Characterization of pelvic floor and genitourinary tissue in a preclinical model of classical Ehlers-Danlos Syndrome
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URI
Date
July 2024
Access
2026-07-01
Authors
Kamath, Soumya
Journal Title
Journal ISSN
Volume Title
Publisher
East Carolina University
Abstract
Classical Ehlers-Danlos syndrome (cEDS) is an inherited connective tissue disorder characterized by collagen abnormalities, leading to tissue fragility. Individuals with cEDS often experience urinary incontinence, pelvic pain, and sexual dysfunction, with these symptoms occurring at a higher prevalence in women (73-89%). This subtype of EDS arises from mutations in the collagen type V (COL5a1) gene, pivotal in fibrillogenesis regulation. The goal of our study is to determine the role of collagen V in the genitourinary tissue of both male and female col5a1 heterozygous mice. We hypothesize lower collagen V levels in cEDS mice would lead to more frequent voiding, decreased bladder contraction, and decreased genital tissue contraction.
In chapter two, we attempted to characterize the bladder and vaginal function of the col5a1 heterozygous (HET) mice at 16-weeks by comparing them to their wild-type (WT) counterparts. We found no disparity in voiding frequency or bladder contraction between the two genotypes. However, we noticed that the HET mice exhibited lower bladder contraction rates upon the release of endogenous neurotransmitters. Interestingly, in the vagina, they displayed higher contraction responses to adrenergic stimulation and were more sensitive to nitic oxide mediated relaxation. We also assessed contractility of the iliococcygeus skeletal muscle of the pelvic floor and found no changes between the HET and WT mice.
In chapter three, we repeated these experiments with male col5a1 heterozygous mice, focusing on bladder and penile smooth muscle function. Our findings mirrored those of the females as both genotypes voided at comparable rates. Additionally, both genotypes had no change in carbachol mediated contractions. However, the HET male bladders consistently contracted at lower rates to electrical field stimulation (EFS) which is mediated by the release of endogenous neurotransmitters. Interestingly, their penises exhibited higher contraction rates in response to adrenergic stimulation and showed no difference in relaxation rates.
In conclusion, our findings suggest that the col5a1 heterozygous mouse model holds considerable potential as an animal model for replicating the genitourinary issues observed in clinical cEDS. Our study has established a foundational framework for future research endeavors to further understand the pathophysiological mechanisms and assess potential therapies to improve cEDS urogenital symptoms.