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Urinary Incontinence In Women: Gene Shows Its Strength In Pelvis

Date:
February 18, 2008
Source:
Journal of Clinical Investigation
Summary:
The quality of life of millions of women is negatively affected by pelvic organ prolapse, which causes symptoms such as urinary incontinence. In women with POP, the main supportive structures of the uterus and vagina, the uterosacral ligaments, are attenuated. Now, mouse studies have shown that the Hoxa11 gene makes a molecular factor essential for USL development, leading to the suggestion that changes in HOXA11-regulated pathways might weaken USLs and thereby cause POP.
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The quality of life of millions of women is negatively affected by pelvic organ prolapse (POP) -- the downward descent of the pelvic organs that causes symptoms such as urinary incontinence.

In women with POP, the uterosacral ligaments (USLs), the main supportive structures of the uterus and vagina, are attenuated. Although changes in the content and quality of the collagen in the connective tissue of USLs have been associated with POP, no molecular mechanism(s) underlying this disorder has been described.

However, Kathleen Connell colleagues, at Yale University School of Medicine, New Haven, have now shown in mice that the protein encoded by the homeobox gene Hoxa11 is an essential molecular factor for the development of USLs, leading them to suggest that changes in HOXA11-regulated pathways might weaken the connective tissue of USLs and thereby cause POP.

In the study, mice lacking Hoxa11 were found to have no USLs and expression of HOXA11 was found to be markedly decreased in the USLs of women with POP. The USLs of women with POP also expressed decreased levels of the collagen type I and collagen type III genes as well as increased levels of the MMP2 gene that enables cells to generate a mediator of connective tissue degradation. Further in vitro analysis indicated that the mouse Hoxa11 gene increased expression of the collagen type III gene and decreased expression of the Mmp2 gene, thereby defining a molecular mechanism regulating the mechanical strength of USLs.

Journal article: HOXA11 is critical for development and maintenance of uterosacral ligaments and deficient in pelvic prolapse, Journal of Clinical Investigation. February 14, 2008.


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Journal of Clinical Investigation. "Urinary Incontinence In Women: Gene Shows Its Strength In Pelvis." ScienceDaily. ScienceDaily, 18 February 2008. <www.sciencedaily.com/releases/2008/02/080215103305.htm>.
Journal of Clinical Investigation. (2008, February 18). Urinary Incontinence In Women: Gene Shows Its Strength In Pelvis. ScienceDaily. Retrieved August 3, 2015 from www.sciencedaily.com/releases/2008/02/080215103305.htm
Journal of Clinical Investigation. "Urinary Incontinence In Women: Gene Shows Its Strength In Pelvis." ScienceDaily. www.sciencedaily.com/releases/2008/02/080215103305.htm (accessed August 3, 2015).

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