Transforming growth factor a1 and extracellular matrix protease expression in the uterosacral ligaments of patients with and without pelvic organ prolapse

Objectives: This study was undertaken to evaluate the expression of transforming growth factor β1 (TGF-β1) and matrix metalloproteinase 9 (MMP-9), key regulators of the extracellular matrix composition, in the uterosacral ligaments (USLs) of women with pelvic organ prolapse (POP) compared with controls. Methods: Under an institutional review board approval, USL samples were obtained from women undergoing vaginal hysterectomy for stage 2 or greater POP (cases, n = 21) and from women without POP undergoing vaginal hysterectomy for benign indications (controls, n = 19). Hematoxylin and eosin and trichrome staining were performed on the USL sections, and the distribution of smooth muscle and fibrous tissue were quantified. Immunohistochemical staining was performed using anti-TGF-β1 and anti-MMP-9 antibodies. The expressions of TGF-β1 and MMP-9 were evaluated by the pathologist, who was blinded to all clinical data. Results: Transforming growth factor β1 expression positively correlated with MMP-9 expression (R = 0.4, P = 0.01). The expressions of TGF-β1 and MMP-9 were similar in subjects with POP versus controls. There was a significant increase in fibrous tissue (P = 0.008) and a corresponding decrease in smooth muscle (P = 0.03), associated with increasing age. The TGF-β1 expression, but not MMP-9 expression, also significantly increased with age (P = 0.02). Discussion: Although our study uncovered age-related alterations in USL composition and TGF-β1 expression, there was no difference in the expression of TGF-β1 or MMP-9 in the subjects with POP versus controls.