Collagen changes in pelvic support tissues in women with pelvic organ prolapse

Abstract

Pelvic organ prolapse is a group of diseases caused by weakened pelvic supportive tissue, but the pathophysiology is not completely understood. Collagen is one of the most important components of the extracellular matrix in connective tissue, as it maintains the supportive functions of the pelvic floor. Collagen I and III are two major subtypes in pelvic tissues. With conflicting results of different studies, changes of their content and ratio are still disputed. The structure of collagen fibrils of pelvic organ prolapse patients become loose, disorderly and discontinuous and become stiffer than control group. Strong mechanical stress and imbalance matrix metalloproteinases /tissue-derived inhibitors of metalloproteinases can lead to collagen anabolism abnormalities causing changes of collagen content and structure. These changes are inter-influenced and are involved by multiple signaling pathways, including TGF-β/Smad, AGE/RAGE, MAPK, PI3K/AKT, and NF-κB. Collagen changes, including content, morphologic and biomechanical changes and catabolism abnormalities, can destroy the supportive function of the pelvic floor and are closely related to the development of pelvic organ prolapse. Epidemiological data also show a genetic predisposition to collagen changes. Research about collagen changes in the pelvic floor supportive tissues is limited and controversial. Small sample sizes and different recruitment criteria, biopsy sites, and research methods make comparisons between various studies difficult. More research concerning collagen changes is needed to better understand the pathogenesis of pelvic organ prolapse.

Keywords: Biomechanics; Collagen; Extracellular matrix; Pelvic organ prolapse; Signaling pathways.