Hum. Reprod. Advance Access published online on December 11, 2007
Human Reproduction, doi:10.1093/humrep/dem370
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Is 
2-macroglobulin important in female stress urinary incontinence?
Department of Obstetrics and Gynecology, Stanford University School of Medicine, 300 Pasteur Drive, H333 Stanford, CA 94305, USA
1 Correspondence address. Tel: +1-650-723-9536; Fax: +1-650-723-7737; E-mail: yanwen{at}stanford.edu
BACKGROUND: Loss of mechanical stability of the urethra and bladder is thought to be important in the development of stress urinary incontinence (SUI). The vaginal wall is the main supporting tissue for pelvic organs and changes in components of supporting tissues are known to be involved in the pathophysiology of SUI.
METHODS: We evaluated changes in expression of 
2-macroglobulin (2-M), a protease inhibitor, in vaginal wall tissues from premenopausal women (aged 42–45 years) with SUI (n = 28) compared with menstrual cycle-matched continent women (controls, n = 29). The distribution of 2-M in vaginal wall tissues and fibroblasts was analysed by immunohistochemistry and immunofluorescence. Expression levels of 2-M mRNA and protein was determined by relative real-time quantitative PCR and enzyme-linked immunosorbent assay, respectively. Protease inhibition was measured to assess bioactivity.
RESULTS: Vaginal wall tissues do express 2-M. Expression of 2-M mRNA and protein was significantly higher in tissues from controls compared to women with SUI in both proliferative and secretory phases (P < 0.05). Protease inhibitory activity of 2-M was significantly higher in tissues from controls compared to women with SUI in the secretory phase (P < 0.05), but we found no difference in the proliferative phase between groups. 2-M protein level was lower in the proliferative phase than the secretory phase in both controls and SUI patients, while for 2-M mRNA this was found only in controls.
CONCLUSIONS: Decreased expression of 2-M mRNA and protein and protease inhibitory activity in the vaginal wall tissues of women with SUI may contribute to the development of SUI.
Key words:
extracellular matrix/stress urinary incontinence/2-macroglobulin/vaginal wall/proteases
Submitted on August 17, 2007; resubmitted on October 15, 2007; accepted on October 19, 2007.