Recovery of Continence Function following Simulated Birth Trauma Involves Repair of Muscle and Nerves in the Urethra in the Female Mouse

Abstract

Background The natural history and the mechanisms behind the alteration of vaginal distension (VD) in a mouse model are not clear. Objective We examined the temporal sequelae of VD and pudendal nerve transection (PNT) on leak-point pressure (LPP) and the muscular and nerve components of the urethra in mice. Design, setting, and participants Seventy-two virgin female C57BL/6 mice were equally distributed into three groups. The VD group underwent VD for 1 h. The PNT group received bilateral PNT. A control group underwent sham VD. Intervention Each group was divided into four subgroups of six mice for measurement of LPP at 0, 4, 10, and 20 d after VD or PNT. Measurements LPP was measured. Morphology and neurofilament-immunoreactive nerve of the urethra were assessed. Results and limitations LPP was decreased at 0, 4, and 10 d but not at 20 d after VD. Decreased LPP persisted to 20 d in the PNT group. The external urethral striated muscle appeared wavy and disrupted in three mice at 0 d, in two mice at 4 d, in one mouse at 10 d, and in one mouse in 20 d after VD. The density of neurofilament-immunoreactive nerve in the urethra was reduced at 4 and 10 d after VD, but not at 20 d, and at 4, 10, and 20 d after PNT compared with the corresponding values of the sham VD group. The limitation of this animal model is that the pelvic floor structure of the mouse is different from that of female humans. Therefore, results of this study should be carefully applied to human subjects. Conclusions VD causes reversible stress urinary incontinence in female mice. Recovery of continence function following VD is associated with repair of the external urethral sphincter and reinnervation of the urethra. This mouse model will be useful for mechanistic investigation and targeting of therapeutic intervention by taking advantage of genetic manipulation.

Ex vivo biomechanical, functional, and immunohistochemical alterations of adrenergic responses in the female urethra in a rat model of birth trauma

“…It was shown that VD decreases leak point pressure (5,17,22) and decreases closure pressure in the middle urethra (17). Histological analyses showed that VD decreases the density of nerve fascicles (5,21) and alters smooth and striated muscle structure (20,36).…”

Expression of Monocyte Chemotactic Protein 3 Following Simulated Birth Trauma in a Murine Model of Obesity

“…Upon urodynamic evaluation, leak point pressure (LPP) decreases to a nadir level four days following VD and recovers by 20 days. 12 The reversibility of SUI after VD in murine models mimics the clinical scenario of SUI recovery following birth trauma in women.…”

Stem Cell Therapy for Stress Urinary Incontinence: A Critical Review

“…Specifically, Pan et al [33] found that, compared with sham-treated counterparts, VD-treated virgin rats exhibited significantly lower urethral resistance, as assessed by LPP test, at 10 days but not at 6 weeks after VD. More recently, Lin et al [37] showed that, compared with sham-treated counterparts, VD-treated virgin mice displayed decreased LPP at 4 and 10 days but not at 20 days post-VD. Thus, VD alone is incapable of creating a rodent model suitable for testing SUI treatment efficacy beyond the 6-week time point.…”