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


METHODS
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.
Department of Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan. Electronic address: d888208@ms45.hinet.net.
Huey-Yi
HY
Chen
Chao-Jung
CJ
Chen
Yu-Ning
YN
Lin
Yung-Hsiang
YH
Chen
Wen-Chi
WC
Chen
Chuan-Mu
CM
Chen
D000818:Animals; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D009218:Myosins / Q000096:biosynthesis; D036801:Parturition; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D014521:Urethra / Q000293:injuries / Q000502:physiology*; D014550:Urinary Incontinence, Stress / Q000503:physiopathology*; D014563:Urodynamics; D014621:Vagina / Q000293:injuries*
D009218:Myosins
Leak point pressure; Maximum urethral closure pressure; Myosin; Stress urinary incontinence; Vaginal distension