Dataset Information

Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina.

ABSTRACT: Pelvic organ prolapse is strongly associated with a history of vaginal delivery. The mechanisms by which pregnancy and parturition lead to failure of pelvic organ support, however, are not known. Recently, it was reported that mice with null mutations in lysyl oxidase-like 1 (LOXL1) develop pelvic organ prolapse. Elastin is a substrate for lysyl oxidase (LOX) and LOXL1, and LOXL1 interacts with fibulin-5 (FBLN5). Therefore, to clarify the potential role of elastic fiber assembly in the pathogenesis of pelvic organ prolapse, pelvic organ support was characterized in Fbln5-/- mice, and changes in elastic fiber homeostasis in the mouse vagina during pregnancy and parturition were determined. Pelvic organ prolapse in Fbln5-/- mice was remarkably similar to that in primates. The temporal relationship between LOX mRNA and protein, processing of LOXL1 protein, FBLN5 and tropoelastin protein, and desmosine content in the vagina suggest that a burst of elastic fiber assembly and cross linking occurs in the vaginal wall postpartum. Together with the phenotype of Fbln5-/- mice, the results suggest that synthesis and assembly of elastic fibers are crucial for recovery of pelvic organ support after vaginal delivery and that disordered elastic fiber homeostasis is a primary event in the pathogenesis of pelvic organ prolapse in mice.

SUBMITTER: Drewes PG

PROVIDER: S-EPMC1851882 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina.

Drewes Peter G PG Yanagisawa Hiromi H Starcher Barry B Hornstra Ian I Csiszar Katalin K Marinis Spyridon I SI Keller Patrick P Word R Ann RA

The American journal of pathology 20070201 2

Pelvic organ prolapse is strongly associated with a history of vaginal delivery. The mechanisms by which pregnancy and parturition lead to failure of pelvic organ support, however, are not known. Recently, it was reported that mice with null mutations in lysyl oxidase-like 1 (LOXL1) develop pelvic organ prolapse. Elastin is a substrate for lysyl oxidase (LOX) and LOXL1, and LOXL1 interacts with fibulin-5 (FBLN5). Therefore, to clarify the potential role of elastic fiber assembly in the pathogene ...[more]

PMID: 17255326

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Project description:To describe pelvic organ prolapse surgical success rates using a variety of definitions with differing requirements for anatomic, symptomatic, or re-treatment outcomes.Eighteen different surgical success definitions were evaluated in participants who underwent abdominal sacrocolpopexy within the Colpopexy and Urinary Reduction Efforts trial. The participants' assessments of overall improvement and rating of treatment success were compared between surgical success and failure for each of the definitions studied. The Wilcoxon rank sum test was used to identify significant differences in outcomes between success and failure.Treatment success varied widely depending on definition used (19.2-97.2%). Approximately 71% of the participants considered their surgery "very successful," and 85.2% considered themselves "much better" than before surgery. Definitions of success requiring all anatomic support to be proximal to the hymen had the lowest treatment success (19.2-57.6%). Approximately 94% achieved surgical success when it was defined as the absence of prolapse beyond the hymen. Subjective cure (absence of bulge symptoms) occurred in 92.1% while absence of re-treatment occurred in 97.2% of participants. Subjective cure was associated with significant improvements in the patient's assessment of both treatment success and overall improvement, more so than any other definition considered (P<.001 and <.001, respectively). Similarly, the greatest difference in symptom burden and health-related quality of life as measured by the Pelvic Organ Prolapse Distress Inventory and Pelvic Organ Prolapse Impact Questionnaire scores between treatment successes and failures was noted when success was defined as subjective cure (P<.001).The definition of success substantially affects treatment success rates after pelvic organ prolapse surgery. The absence of vaginal bulge symptoms postoperatively has a significant relationship with a patient's assessment of overall improvement, while anatomic success alone does not.II.

Dataset Information

Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina.

Publications

Pelvic organ prolapse in fibulin-5 knockout mice: pregnancy-induced changes in elastic fiber homeostasis in mouse vagina.

Similar Datasets

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