Urethral Dysfunction in Female Mice with Estrogen Receptor β Deficiency

Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ER beta in stress urinary incontinence (SUI). Wild-type (ER beta(+/+)) and knockout (ER beta(-/-)) female mice were generated (aged 6-8 weeks, n = 6) and urethral function and protein expression were measured. Leak point pressures (LPP) and maximum urethral closure pressure (MUCP) were assessed in mice under urethane anesthesia. After the measurements, the urethras were removed for proteomic analysis using label-free quantitative proteomics by nano-liquid chromatography-mass spectrometry (LC-MS/MS) analysis. The interaction between these proteins was further analysed using MetaCore. Lastly, Western blot was used to confirm the candidate proteins. Compared with the ER beta(+/+) group, the LPP and MUCP values of the ER beta(-/-) group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ER beta(-/-) female mice; 57 proteins were up-regulated and 28 were downregulated. The majority of the ER beta knockout-modified proteins were involved in cell-matrix adhesion, metabolism, immune response, signal transduction, nuclear receptor translational regelation, and muscle contraction and development. Western blot confirmed the up-regulation of myosin and collagen in urethra. By contrast, elastin was down-regulated in the ER beta(-/-) mice. This study is the first study to estimate protein expression changes in urethras from ER beta(-/-) female mice. These changes could be related to the molecular mechanism of ER beta in SUI.