Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse
Open Access
- 1 October 2008
- journal article
- Published by American Physiological Society in American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Vol. 295 (4), R1351-R1358
- https://doi.org/10.1152/ajpregu.90447.2008
Abstract
Matrix metalloprotease (MMP) activity is increased in the postpartum vagina of wild-type (WT) animals. This degradative activity is also accompanied by a burst in elastic fiber synthesis and assembly. The mechanisms that precipitate these changes are unclear. The goals of this study were to determine how vaginal distention (such as in parturition) affects elastic fiber homeostasis in the vaginal wall and the potential significance of these changes in the pathogenesis of pelvic organ prolapse. Vaginal distention with a balloon simulating parturition resulted in increased MMP-2 and MMP-9 activity in the vaginal wall of nonpregnant and pregnant animals. This was accompanied by visible fragmented and disrupted elastic fibers in the vaginal wall. In nonpregnant animals, the abundant amounts of tropoelastin and fibulin-5 in the vagina were not increased further by distention. In contrast, in pregnant animals, the suppressed levels of both proteins were increased 3-fold after vaginal distention. Distention performed in fibulin-5-deficient ( Fbln5−/−) mice with defective elastic fiber synthesis and assembly induced accelerated pelvic organ prolapse, which never recovered. We conclude that, in pregnant mice, vaginal distention results in increased protease activity in the vaginal wall but also increased synthesis of proteins important for elastic fiber assembly. Distention may thereby contribute to the burst of elastic fiber synthesis in the postpartum vagina. The finding that distention results in accelerated pelvic organ prolapse in Fbln5−/−animals, but not in WT, indicates that elastic fiber synthesis is crucial for recovery of the vaginal wall from distention-induced increases in vaginal protease activity.Keywords
This publication has 33 references indexed in Scilit:
- Levator ani muscle and connective tissue changes associated with pelvic organ prolapse, parity, and aging in the squirrel monkey: a histologic studyAmerican Journal of Obstetrics and Gynecology, 2007
- Pelvic Organ Prolapse in Fibulin-5 Knockout Mice: Pregnancy-Induced Changes in Elastic Fiber Homeostasis in Mouse VaginaThe American Journal of Pathology, 2007
- Functional bowel and anorectal disorders in patients with pelvic organ prolapse and incontinenceAmerican Journal of Obstetrics and Gynecology, 2005
- Effect of vaginal distension on blood flow and hypoxia of urogenital organs of the female ratJournal of Applied Physiology, 2005
- Is the histomorphological concept of the female pelvic floor and its changes due to age and vaginal delivery correct?Neurourology and Urodynamics, 2004
- Elastic fiber homeostasis requires lysyl oxidase–like 1 proteinNature Genetics, 2004
- Functional and Neuroanatomical Effects of Vaginal Distention and Pudendal Nerve Crush in the Female RatJournal of Urology, 2003
- Long-Term Effect of Ovariectomy and Simulated Birth Trauma on the Lower Urinary Tract of Female RatsJournal of Urology, 2002
- Fibulin-5 is an elastin-binding protein essential for elastic fibre development in vivoNature, 2002
- Relaxin Increases the Accumulation of New Epithelial and Stromal Cells in the Rat Cervix during the Second Half of PregnancyEndocrinology, 1998