Urethral dysfunction in female mice with estrogen receptor β deficiency

Yung-Hsiang Chen; Chao-Jung Chen; Shuyuan Yeh; Yu-Ning Lin; Yang-Chang Wu; Wen-Tsong Hsieh; Bor-Tsang Wu; Wen-Lung Ma; Wen-Chi Chen; Chawnshang Chang; Huey-Yi Chen

doi:10.1371/journal.pone.0109058

Urethral dysfunction in female mice with estrogen receptor β deficiency

PLoS One. 2014 Oct 2;9(9):e109058. doi: 10.1371/journal.pone.0109058. eCollection 2014.

Authors

Affiliations

¹ Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan; Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
² Department of Urology, George H Whipple Laboratory for Cancer Research, Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States of America.
³ Graduate Institute of Integrated Medicine, College of Chinese Medicine, School of Pharmacy, College of Pharmacy, Department of Pharmacology, Department of Physical Therapy, Graduate Institute of Rehabilitation Science, China Medical University, Taichung, Taiwan.
⁴ Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan.
⁵ Departments of Medical Research, Urology, and Obstetrics and Gynecology, Sex Hormone Research Center, China Medical University Hospital, Taichung, Taiwan; Department of Urology, George H Whipple Laboratory for Cancer Research, Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York, United States of America.

Abstract

Estrogen has various regulatory functions in the growth, development, and differentiation of the female urogenital system. This study investigated the roles of ERβ in stress urinary incontinence (SUI). Wild-type (ERβ(+/+)) and knockout (ERβ(-/-)) 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 ERβ(+/+) group, the LPP and MUCP values of the ERβ(-/-) group were significantly decreased. Additionally, we identified 85 differentially expressed proteins in the urethra of ERβ(-/-) female mice; 57 proteins were up-regulated and 28 were down-regulated. The majority of the ERβ 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 ERβ(-/-) mice. This study is the first study to estimate protein expression changes in urethras from ERβ(-/-) female mice. These changes could be related to the molecular mechanism of ERβ in SUI.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Down-Regulation
Estrogen Receptor beta / deficiency*
Estrogen Receptor beta / metabolism
Female
Genotype
Mice, Inbred C57BL
Mice, Mutant Strains
Pressure
Proteins / metabolism
Proteomics
Up-Regulation
Urethra / metabolism*
Urethra / physiopathology*
Urodynamics

Substances

Estrogen Receptor beta
Proteins

Grants and funding

This work was supported in part by Taiwan National Science Council (NSC101-2314-B-039-018 and NSC102-2320-B-039-025), China Medical University Hospital (DMR-103-063), and Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH102-TD-B-111-004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.