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BOR - Papers in Press, published online ahead of print November 14, 2007.
Biol Reprod 2007, 10.1095/biolreprod.107.063024
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biolreprod.107.063024v1
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BIOLOGY OF REPRODUCTION 78, 521–528 (2008)
DOI: 10.1095/biolreprod.107.063024
© 2008 by the Society for the Study of Reproduction, Inc.

Regulation of Elastolytic Proteases in the Mouse Vagina During Pregnancy, Parturition, and Puerperium1

Cecilia K. Wieslander , Spyridon I. Marinis , Peter G. Drewes , Patrick W. Keller , Jesús F. Acevedo , and R. Ann Word 2

Division of Urogynecology and Reconstructive Surgery, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas 75390

ABSTRACT

Recent evidence indicates that failure of elastic fiber assembly and synthesis is involved in the pathophysiology of pelvic organ prolapse in mice. It has been long been hypothesized that parturition-induced activation of proteases in the vaginal wall and its supportive tissues may contribute to pelvic organ prolapse in women. In this investigation, we determined the expression of matrix metalloproteases with elastase activity (matrix metalloproteinase [MMP] 2, MMP9, and MMP12) and their inhibitors in the vaginal wall of nonpregnant, pregnant, and postpartum mice. Data obtained using mRNA levels and enzyme activity measurements indicate that MMP2, MMP9, and 21- to 24-kDa caseinolytic serine proteases are regulated in vaginal tissues from pregnant and postpartum mice. Although suppressed during pregnancy and the early postpartum time period, MMP2 and MMP9 enzyme activities are increased after 48 h, a time when mRNA levels of protease inhibitors (tissue inhibitor of MMP2 [Timp2], cystatin C [Cst3], and alpha-1 antitrypsin [Serpina1]) are decreased. We conclude that recovery of the vaginal wall from pregnancy and parturition requires increased elastic fiber assembly and synthesis to counteract the marked increase in elastolytic activity of the postpartum vagina.

elastic fibers, matrix metalloprotease, pelvic organ prolapse, vagina, zymography

FOOTNOTES

1Supported by NIH AG 028048.

Correspondence: 2R. Ann Word, Division of Urogynecology and Reconstructive Surgery, Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9032. FAX: 214 648 9242; e-mail: ruth.word{at}utsouthwestern.edu






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Copyright © 2008 by the Society for the Study of Reproduction.