Proteomic analysis related to stress urinary incontinence following vaginal trauma in female mice

Abstract

Objective: The molecular mechanisms underlying stress urinary incontinence (SUI) are not clear. In light of the limited availability of human tissue for study, we explored the changes in the urethra of C57BL/6 mice with experimentally induced SUI.

Study design: Twelve virgin female mice were randomized into two groups: one group undergoing vaginal distension (VD) for 1h with an 8-mm dilator, and a non-instrumented control group. Four days after VD, leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in these mice under urethane (1g/kg, i.p.) anesthesia. After measuring LPP and MUCP, the animals were sacrificed, and the urethras were removed for proteomic analysis using 2-dimensional differential gel electrophoresis (2D DIGE) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology. Lastly, interaction between these proteins was further analyzed using MetaCore.

Results: LPP and MUCP values were significantly decreased in the 8-mm VD groups compared with the non-instrumented control group. Sixty-eight differentially expressed proteins of urethra from female mice with and without VD were identified. Of these, 19 proteins were up-regulated and 49 were down-regulated. The majority of the VD-induced proteins were involved in generation of precursor metabolites and energy, oxidation of reduction, regulation of apoptosis, and glycolysis. Myosin expression in the urethra was significantly decreased in the 8-mm VD group as compared with the control group.

Conclusions: As a model of simulated birth trauma, VD can induce SUI in female mice. Under-expression of myosin plays a plausible role in the pathogenesis of SUI following vaginal trauma.

Keywords: Leak point pressure; Maximum urethral closure pressure; Myosin; Stress urinary incontinence; Vaginal distension.