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Diminished vaginal HOXA13 expression in women with pelvic organ prolapse

Connell, Kathleen A. MD1; Guess, Marsha K. MD1; Tate, Alison MD1; Andikyan, Vaagn MD1; Bercik, Richard MD1; Taylor, Hugh S. MD2

doi: 10.1097/gme.0b013e31818fb0c2

Objective: Homeobox genes are transcriptional regulators that orchestrate embryonic development. The HOXA13 gene is responsible for the development of the vagina and regulates extracellular matrix constituents. We hypothesized that vaginal expression of HOXA13 may be decreased in women with pelvic organ prolapse (POP) and sought to determine if hypoestrogenism affects its expression.

Methods: Biopsy specimens were obtained from the anterior apex of the vagina from women with and without POP. Immunohistochemistry and real-time polymerase chain reaction were used to determine HOXA13 expression in premenopausal controls, in premenopausal women receiving leuprolide acetate, and in premenopausal and postmenopausal women with POP.

Results: HOXA13 was expressed in all specimens. HOXA13 expression was 14-fold lower in premenopausal women with prolapse than in premenopausal controls (P < 0.001). In both POP groups, HOXA13 expression was lower than in the leuprolide group (P ≤ 0.001). There were no differences in HOXA13 expression between premenopausal controls and women treated with leuprolide acetate (P = 1.0) or between the premenopausal and postmenopausal POP group (P = 1.0).

Conclusions: Vaginal HOXA13 expression is diminished in women with POP compared with women with normal support. In women with POP, expression of HOXA13 was not affected by menopause. Expression of HOXA13 was also not affected by exposure to leuprolide acetate, suggesting that estrogen and HOXA13 work through separate pathways in the extracellular matrix metabolism of the vagina. Understanding genetic predispositions to developing POP may identify younger patients at risk who may benefit from preventive strategies such as weight loss or smoking cessation and not necessarily from estrogen therapy.

From the Divisions of 1Urogynecology and Reconstructive Pelvic Surgery and 2Reproductive Endocrinology and Infertility, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT.

Received August 13, 2008; revised and accepted September 22, 2008.

Funding/support:This work was supported by the National Institute of Child Health and Human Development Women's Reproductive Health Research Career Development Program grant 5K12HD047018 (KAC), NIH grants R01 HD36887 and R01 ES010610 (to H.S. Taylor), and NIH/NCRR-CTSA UL1 RR024139 and RWF-Harold Amos Faculty Development Grant (MKG).

Financial disclosure: None reported.

Address correspondence to: Kathleen A. Connell, MD, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, 333 Cedar St, FMB 307, New Haven, CT 06520. E-mail:

©2009The North American Menopause Society