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"Alterations of the vaginal wall and uterosacral ligament of women with severe pelvic organ prolapse - a morphological and molecular approach to elastic fibers"

Grant number: 22/02368-4
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): June 01, 2023
Effective date (End): February 28, 2026
Field of knowledge:Health Sciences - Medicine
Principal Investigator:Sílvio Roberto Consonni
Grantee:Lizandra Maia de Sousa
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Introduction: Pelvic organ prolapse (POP) is a pathology characterized by the descent of one or more vaginal compartments. This descent is usually accompanied by weakness of the endopelvic fascia, which can result in prolapse of one or more pelvic organs, such as the bladder, uterus, rectum, and bowel through the vaginal canal. The etiology of genital prolapse is multifactorial, in addition to age, other factors such as genetic predisposition, obesity, infection and parity have been related to its progression. The bony pelvis provides anchorage points for the fascial coverings of the pelvic muscles that perform supportive actions with respect to Organs pelvic organs. Pelvic support is ensured by the presence of the uterosacral ligaments, which support the upper portion of the vagina and the cervix and the lateral pelvic wall. The vagina plays an important role in balancing and supporting the viscera and pelvic organs in women. Changes in extracellular matrix (ECM) components, such as changes in elastic fibers due to dysregulation between gelatinases, matrix metalloproteinases 2 and 9 (MMP-2 and -9), and their inhibitors of metalloproteinases 1 and 2 (TIMP-1 and -2), in the uterosacral ligaments and in the vaginal compartments can lead to the loss of homeostasis and, consequently, the loss of biomechanical tissue support and structural functions, contributing to the genesis or progression of POP. Objective: This study seeks to understand how the structure, function and activity of ECM molecules can provide the basis for understanding POP, which can be clinically evaluated for interventions aimed at improving the quality of life of women with POP. Materials and Methods: A prospective study, with consecutive sampling, will be carried out in 50 women with genital prolapse (POP-Q case group 3 and 4) and 50 women in the control group (POP-Q category 0 and 1) in the CAISM with analysis of the uterosacral ligament and vaginal wall embedded in the material during elective surgery. Morphological analyzes will be carried out using light and transmission electron microscopy; immunolocalization of tropoelastin, fibrillin-1, fibulin-5 and LOXL1 by immunohistochemistry; immunochemistry of tropoelastin, fibrillin-1, fibulin-5 and LOXL1, TIMP-1 and TIMP-2 by means of Western Blotting; evaluation of enzymatic activity of MMP-2, MMP-9, through zymography and quantitative analysis by Real-Time PCR of tropoelastin, fibulin-5, fibrillin-1, fibrillin-2, MAGP1, MAGP2, LOX, LOXL1, TIMP- 1, TIMP-2, MMP-9, MMP-2 and IL-6. Relative gene expression data will be compared between case and control groups using the Kruskal-Wallis test followed by the Mann-Whitney test. Statistical significance will be defined as p < 0.05.

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