title: Urethral proteomic analysis in ovariectomized mice administered 17β-oestradiol replacement therapy.
abstract: The molecular mechanism by which 17β-oestradiol (E2) increases urethral tone is unclear. As human tissue is limited in availability, we explored changes in the urethras of ovariectomized (OVX) mice. Twenty-four virgin female mice were randomised into three groups: mice with a sham operation only (control), OVX mice without E2 replacement (OVX), and OVX mice with E2 replacement (OVX + E2). Two weeks after the ovariectomy, mice received either E2 or placebo for 4 weeks. Leak point pressure (LPP) and maximum urethral closure pressure (MUCP) were assessed in these mice at 6 weeks after OVX, under anaesthesia. After measurements were recorded, the animals were sacrificed and the urethras were removed for proteomic and further analyses. LPP and MUCP values were significantly higher in OVX + E2 group than in OVX group. Fourteen differentially expressed proteins within the urethras of mice from OVX and OVX + E2 groups were identified; six proteins were upregulated and eight proteins were down-regulated. Most E2-induced proteins are involved in proteolysis, development, neurophysiological processes, transcription, and the cell cycle. Expression of survival motor neuron (SMN) protein in the urethra was significantly increased in OVX + E2 group compared to OVX group. OVX can impair urethral tone in female mice. E2 supplementation in OVX mice rescued urethral tone. E2-mediated increase in urethral tone in OVX mice involves overexpression of SMN, decreased proteolysis and promotion of development, neurophysiological processes, and transcription in the urethra. The urethra actively undergoes multiple biological processes in response to OVX and OVX with E2 stimuli. Impact statement Estrogens are known to modulate lower urinary tract trophicity. Although treatments with 17β-oestradiol (E2) result in an increase in urethral tone, the mechanism by which E2 increases urethral tone is still not completely understood. Ovariectomy can impair urethral tone in female mice. E2 supplementation in ovariectomized mice rescued urethral tone. E2-mediated increase in urethral tone in ovariectomized mice involves overexpression of survival motor neuron, decreased proteolysis and promotion of development, neurophysiological processes, and transcription in the urethra. This information will offer clues about pathogenesis of stress urinary incontinence after menopause and will open additional avenues for novel research and potential therapies.
authors.affiliation: a Departments of Obstetrics and Gynecology , Medical Research, and Urology, Sex Hormone Research Center, China Medical University Hospital , Taichung , Taiwan.|b Proteomics Core Laboratory, College of Chinese Medicine, Research Center for Chinese Medicine & Acupuncture, Graduate Institute of Integrated Medicine , China Medical University , Taichung , Taiwan.
authors.forename: Huey-Yi
authors.initials: HY
authors.lastname: Chen
authors.affiliation: b Proteomics Core Laboratory, College of Chinese Medicine, Research Center for Chinese Medicine & Acupuncture, Graduate Institute of Integrated Medicine , China Medical University , Taichung , Taiwan.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Lin
authors.affiliation: a Departments of Obstetrics and Gynecology , Medical Research, and Urology, Sex Hormone Research Center, China Medical University Hospital , Taichung , Taiwan.|b Proteomics Core Laboratory, College of Chinese Medicine, Research Center for Chinese Medicine & Acupuncture, Graduate Institute of Integrated Medicine , China Medical University , Taichung , Taiwan.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chen
authors.affiliation: b Proteomics Core Laboratory, College of Chinese Medicine, Research Center for Chinese Medicine & Acupuncture, Graduate Institute of Integrated Medicine , China Medical University , Taichung , Taiwan.
authors.forename: Shih-Jing
authors.initials: SJ
authors.lastname: Wang
authors.affiliation: a Departments of Obstetrics and Gynecology , Medical Research, and Urology, Sex Hormone Research Center, China Medical University Hospital , Taichung , Taiwan.|b Proteomics Core Laboratory, College of Chinese Medicine, Research Center for Chinese Medicine & Acupuncture, Graduate Institute of Integrated Medicine , China Medical University , Taichung , Taiwan.
authors.forename: Chao-Jung
authors.initials: CJ
authors.lastname: Chen
authors.affiliation: a Departments of Obstetrics and Gynecology , Medical Research, and Urology, Sex Hormone Research Center, China Medical University Hospital , Taichung , Taiwan.|b Proteomics Core Laboratory, College of Chinese Medicine, Research Center for Chinese Medicine & Acupuncture, Graduate Institute of Integrated Medicine , China Medical University , Taichung , Taiwan.|c Department of Psychology, College of Medical and Health Science , Asia University , Taichung , Taiwan.
authors.forename: Yung-Hsiang
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000818:Animals; D015180:Electrophoresis, Gel, Two-Dimensional; D004958:Estradiol / Q000494:pharmacology*; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D020543:Proteome; D011897:Random Allocation; D014521:Urethra / Q000187:drug effects* / Q000378:metabolism*; D014550:Urinary Incontinence, Stress / Q000209:etiology; D014563:Urodynamics
chemical_list: D004967:Estrogens; D020543:Proteome; D004958:Estradiol
keywords: Estradiol; leak point pressure; maximum urethral closure pressure; ovariectomy; stress urinary incontinence