transforming-growth-factor-beta and Uterine-Prolapse

Alterations in collagen synthesis and metabolism have previously been reported in patients with pelvic organ prolapse (POP) and/or urodynamic stress incontinence (USI). Since urinary incontinence does not always associate with POP, the objective of this study was to examine connective tissues from patients with USI plus POP, and patients with prolapse only.. Biopsies from the uterosacral ligaments were obtained during the operation from POP patients (n =28), and from continent women (control group, n =12) who underwent surgery for other benign reasons. POP patients were classified following urodynamic tests and symptom questionnaire with respect to the presence (n =14) or absence (n =14) of USI. N-terminal propeptides of collagen (PINP and PIIINP), TGF-beta and leptin were measured in plasma. Hydroxyproline and glycosaminoglycan (GAGs) concentrations and total hexosaminidase activity were measured in tissue samples. Histological sections were prepared using Masson's trichrome technique, and digitised solutions were used for imaging provided by Soft Imaging System GmBh. Statistical evaluations were made by the Kruskal-Wallis test.. A significant decrease in hydroxyproline content was found in USI+POP women in comparison to controls (p<0.05). In contrast, histopathological examination revealed an increased density of collagen in USI+POP patients. Hexosaminidase activity was decreased in both groups with POP, but no change in the amount of GAGs was observed. Markers of collagen synthesis (PINP, PIIINP), and factors related to the collagen synthesis (TGF-beta, leptin) remained unaltered.. Our biochemical and morphological findings suggest a different organisation of collagen fibres in tissues of patients with USI+POP, when compared with both the controls and the POP patients.

Topics: Biopsy; Collagen; Connective Tissue; Female; Glycosaminoglycans; Hexosaminidases; Humans; Hydroxyproline; Leptin; Middle Aged; Statistics, Nonparametric; Transforming Growth Factor beta; Urinary Incontinence; Uterine Prolapse

To determine the mRNA expression of lysyl oxidase (LOX) and transforming growth factor beta2 (TGF beta2) in subjects with advanced pelvic organ prolapse as compared to asymptomatic controls.. Seventeen women undergoing vaginal hysterectomy were recruited for the study. Nine women with grade > or = 3 pelvic organ prolapse by the Baden-Walker grading scale were recruited. Eight subjects without pelvic organ prolapse or urinary incontinence undergoing hysterectomy for other indications were recruited as asymptomatic controls. A 1-cm portion of the bilateral distal uterosacral ligaments was excised and immediately frozen at -80 degrees C. Total RNA was extracted, quantified and subjected to reverse transcription for cDNA synthesis. beta-Actin was used as the reference for the semiquantitative analysis. Known volumes of the polymerase chain reaction (PCR) products for each reaction were electrophoresed in agarose gels stained with ethidium bromide and photographed with a digital camera. The optical density for each sample was measured by using computerized image analysis software. The relative abundance of each specific message was calculated as the ratio of PCR product for LOX or TGF beta2 divided by the amount of PCR product for beta-actin from the same sample.. The mean age of the study subjects was 55.7 years (38-67) versus 47.1 for the controls (44-54). Mean parity was 4.4 for the study subjects and 2.7 for the controls. Seventy-eight percent of the study subjects were postmenopausal, and 14% of the controls postmenopausal. All postmenopausal subjects had at least 1 month of estrogen therapy prior to surgery. The mean LOX/beta-actin ratio for the study group was 0.35 as compared to 0.72 for the control group. This was statistically significant with a p value of 0.049. The mean TGF beta2/beta-actin ratio for the study group was 0.12 as compared to 0.20 for the control group. This was not statistically significant (p = 0.46).. Patients with severe pelvic organ prolapse (grade > or = 3) have a significant reduction in the mRNA expression of lysyl oxidase as compared to asymptomatic controls. The mRNA expression of TGF beta2 was not statistically different between the 2 groups. These findings lend further credence to the concept of specific biochemical changes in the pelvic floor in women with pelvic organ prolapse.

Topics: Adult; Aged; Case-Control Studies; Cohort Studies; Female; Gene Expression; Humans; Hysterectomy, Vaginal; Menopause; Middle Aged; Parity; Pelvic Floor; Pregnancy; Prospective Studies; Protein-Lysine 6-Oxidase; RNA, Messenger; Transforming Growth Factor beta; Uterine Prolapse