Diminished vaginal HOXA13 expression in women with pelvic organ prolapse.
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 <or= 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.
Division of Urogynecology and Reconstructive Pelvic Surgery, Department of Obstetrics, Gynecology & Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA. kathleen.connell@yale.edu
Kathleen A
KA
Connell
Marsha K
MK
Guess
Alison
A
Tate
Vaagn
V
Andikyan
Richard
R
Bercik
Hugh S
HS
Taylor
D000328:Adult; D016022:Case-Control Studies; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D014596:Uterine Prolapse / Q000378:metabolism*; D014621:Vagina / Q000378:metabolism*
D018398:Homeodomain Proteins; C099959:homeobox protein HOXA13