Differential expression profiling of matrix metalloproteinases and tissue inhibitors of metalloproteinases in females with or without pelvic organ prolapse

Abstract

Abstract. Pelvic organ prolapse (POP) is a common disorder that can disturb the health and quality of life of females. However, the basic pathophysiology and underlying mechanism of POP are not fully understood. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) have been reported to be associated with the onset and development of POP. In the present study, to characterize the differential expression profile of MMPs and TIMPs in female patients with and without POP, a total of 72 POP patients were sampled as a patient group and 72 non-POP patients that underwent hysterectomy due to benign tumors were sampled as a control group. Immunohistochemistry and polymerase chain reaction analysis were used to detect the expression levels of MMP-1, -2, -3 and -9 as well as TIMP-1 protein and mRNA in the anterior vaginal wall tissues. The expression levels of MMP-1, -2, -3 and -9 in the patient group were found to be significantly higher than those in the control group. By contrast, TIMP-1 expression levels in the patient group were significantly lower than those in the control group. Correlational analysis revealed a significantly positive correlation among the expression levels of MMP-2, -3 and -9. TIMP-1 expression levels were significantly negatively correlated with the expression levels of MMP-3 and -9. In addition, the expression levels of MMP-1 exhibited a positive correlation with those of MMP-2, -3 and -9, but a negative correlation with those of TIMP-1. The results demonstrated that the increased expression levels of MMPs and the reduced expression levels of TIMPs were directly associated with the presence of uterine prolapse, indicating that the differential expression levels of MMPs and TIMPs were correlated with the occurrence and development of POP. This data may assist in elucidating the molecular mechanism of MMP and TIMP involvement in POP, and also provide an underlying theoretical basis for the prevention and treatment of POP. IntroductionPelvic organ prolapse (POP) is the displacement of pelvic organs caused by various types of damage to the pelvic floor fascia and ligaments, which have failed to fully recover, or by weakened supporting structures, due to hypotonia. The predominant clinical manifestations are anterior and/or posterior vaginal wall prolapse as well as uterine prolapse (1). POP, a pelvic floor dysfunction (PFD) disorder, is a global health problem that affects 50% of parous females. It contributes to reduced quality of life and is a major reason for gynecological surgery in aging females (2). The pelvic organs are supported by pelvic floor muscles, the bony pelvis, ligaments and fascial supports. Abnormalities in the connective tissues of the pelvic support system have been suggested to contribute to the genesis of POP (3,4). The exact pathophysiology and natural history of POP, however, are not fully understood.The fascia and ligaments in the bladder and urethra are mainly composed of connective tissue, and the main structural protein is type I collagen...

Matrix Metalloproteinase‐1 Expression in Women With and Without Pelvic Organ Prolapse: A Systematic Review and Meta‐analysis

“…After assessing the full texts of nine potentially relevant articles, we determined five eligible case–control studies. Of the four excluded studies, one was irrelevant to MMP‐1 expression, one was excluded because it was a repeatedly published literature source, and two investigations were excluded because the numbers or percentages of cases and controls in the different staining groups were not reported . Although two of the studies were by the same first author and conducted in the same country, the included participants were different.…”

Assessment of Metalloproteinase Matrix 9 (MMP9) Gene Polymorphisms Risk Factors for Pelvic Organ Prolapse in the Brazilian Population

“…15 Nevertheless, some studies compared the MMP9 activity in the vaginal tissues of women with and without a genital prolapse and found an increase in MMP9 activity in association with this disease. 20,22 In our review, 1 study that aimed to establish a relationship between the rs17576 and rs3918242 MMP9 polymorphisms and the risk of POP was performed by Chen et al, 23 which included 92 Chinese women with POP and 152 women without the disease. The authors observed, after a binary logistic regression, that the MMP9 rs17576 polymorphism seemed to be associated with POP, but did not find any association between the MMP9 rs3918242 polymorphism and the risk of POP, which is in line with the present study.…”

Association between col1a2 Polymorphism and the Occurrence of Pelvic Organ Prolapse in Brazilian Women

“…2 In addition, POP is the main reason for surgery in aging women. 3 The etiology of POP is considered multifactorial, and several risk factors, such as advanced age, pregnancy, obesity, neuropathies, ethnicity, hysterectomy, instrumental delivery, and menopause, have been identified. Recent evidence suggests the existence of a genetic component with a 3.2-to 2.4-fold increased risk for the mothers and sisters of affected women, respectively.…”

“…The high prevalence of POP in patients with type I and III collagen disorders, such as Ehlers-Danlos and Marfan syndromes, corroborates the importance of studying the genetic background of patients with the disease. 3,4 Older age and parity are the most significant etiological factors, but they do not fully explain the origin and progression of pelvic floor dysfunction in all women, since POP has been observed in nulliparous women and has been absent in many multiparous women. 5 The main mechanism of pelvic floor dysfunction is the weakening of the structures that support the pelvic organs: connective tissue in the form of ligaments and endopelvic fascia, and the levator ani muscles.…”