Rahn DD, Acevedo JF, Word RA. Effect of vaginal distention on elastic fiber synthesis and matrix degradation in the vaginal wall: potential role in the pathogenesis of pelvic organ prolapse. Am J Physiol Regul Integr Comp Physiol 295: R1351-R1358, 2008. First published July 16, 2008 doi:10.1152/ajpregu.90447.2008 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 Ϫ/Ϫ ) 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 Ϫ/Ϫ 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. childbirth trauma; MMP9; protease; pregnancy PELVIC ORGAN PROLAPSE IS A common problem for women with significant psychological, social, and financial implications (12,26,29). Whereas many factors appear to incite or promote the progression of prolapse, the two major risk factors for pelvic organ prolapse are history of vaginal delivery and aging. Although cesarean delivery does not completely protect the pelvic floor from the adverse effects of pregnancy, it is universally agreed that vaginal delivery has a deleterious impact on the development of pelvic organ prolapse in women, and this impact may not be of clinical significance until decades after delivery. The mechanisms by which childbirth leads to failure of pelvic organ support, however, are not well understood (3,26).Mice with null mutations in genes encoding lysyl oxidase like 1 (LOXL1) (15, 16) or fibulin-5 (FBLN5) (11) develop pelvic organ prolapse. Since both proteins play important roles in elastic fiber synthesis and assembly (19,30), these findings indicate that fa...