Expression Of Elastin, Fibulin-5 And Lysyl Oxidase-like 1 In The Uterosacral Ligaments Of Postmenopausal Women With And Without Pelvic Organ Prolapse

Background:Pelvic floor disorders comprise a wide spectrum of interrelated clinical conditions including pelvic organ prolapse(POP), urinary incontinence, fecal incontinence, voiding dysfunction, defecatory dysfunction, and sexual dysfunction. They affect nearly one-third of premenopausal women and nearly half of postmenopausal women. The POP is distressing morbidity that affects the quality of life in sufferers. The integrity of the pelvic organs and their supportive connective tissues is essential for maintaining their anatomic position. Pelvic organ prolapse is associated with defects in connective tissues including elastic fibers. Traditionally, research into the role of connective tissues in pelvic floor disorders has focused on changes in collagen. Published reports showed decreased collagen content in the vesicovaginal fascia and round ligaments in women with pelvic floor diseases. In addition to collagen, female pelvic tissues are rich in elastic fibers. In recent research, the content of elastin and its structure, function in the supportive connective tissues of pelvic organs have been focused on. Elastic fibres are designed to maintain elastic function for a lifetime. Indeed, loss of elasticity due to degradative changes is a major contributing factor in ageing of connective tissues, in the development of aortic aneurysms and lung emphysema, and in degenerative changes in sun-damaged skin. The importance of elastic fibres is further highlighted by the severe heritable connective tissue diseases caused by mutations in components of elastic fibres. The precise cause of POP has not been delineated, it is most likely the manifestation of multiple factors.Objective:Pelvic organ prolapse is distressing morbidity that affects the quality of life in sufferers. Pelvic organ prolapse is associated with defects in connective tissues including elastic fibers.The purpose of this study was to investigate expression of fibulin-5 and lysyl oxidase-like 1, which play an essential role in synthesis and assembly of elastic fibers, in the uterosacral ligaments taken from women with advanced pelvic organ prolapse compared with controls.Methods:1,Specimens were obtained prospectively during abdominal or transviginal hysterectomy from 30 women with advanced pelvic organ prolapse and 30 controls matched to POP group for age and parity among postmenopausal women with benign gynecologic diseases.2,Expression of protein of elastin, fibulin-5 and lysyl oxidase-like 1 in uterosacral ligaments were measured by immunohistochemistry. Immunolabeling intensity was classified as (-) negative, (+) weak, (++) moderate or (+++) strong.3,For statistical analyses, Student's t-test, chi-square test, Mann-Whitney U test and Fisher's exact test were used for statistical analysis, which was performed using SPSS statistical software. A P-value<0.05 was considered statistically significant.Results:Elastin, fibulin-5 and LOXL1 were detected in the uterosacral ligaments of most analyzed samples taken from women without POP. We had detected a decreased, even absent, expression of fibulin-5 and LOXL1 in uterosacral ligaments taken from women with POP, in despite of positive expression of elastin. There was a decrease in positive percentage of LOXL1 in POP group (23.3%) compared with controls (60%) (p=0.004). With immunolabeling intensity classified as (-) negative, (+) weak, (++) moderate or (+++) strong, there was a decrease in expression of fibulin-5 in the POP group (p=0.049). We also detected a significant lower expression of LOXL1 in POP group (p=0.001).Conclusion:1,The expression of elastin in uterosacral ligaments in patients with pelvic organ prolapse was not significantly decreased, which indicates that not the quantity, but the structure or remodeling disorder of elastin may occur in POP patients.2,There was decreased expression of fibulin-5 and lysyl oxidase-likel in uterosacral ligaments in patients with pelvic organ prolapse, which may suggest the possibility of defects in elastic fiber remodeling in postpartum and contribute to POP.