Evaluation of extracellular matrix protein expression and apoptosis in the uterosacral ligaments of patients with or without pelvic organ prolapse

Introduction and hypothesis This study aimed to compare the expression levels of extracellular matrix (ECM) and apoptosis proteins in the uterosacral ligament (USL) of patients with and without pelvic organ prolapse (POP). Methods The USL were obtained from patients with POP-Q ≥ III ( n = 35) and without POP ( n = 20). Immunohistochemistry (IHC) staining and RT-qPCR were conducted to assess the protein and mRNA levels, respectively. The levels of type I collagen (COLI), type III collagen (COLIII), matrix metalloproteinase (MMP)1, MMP2, MMP9, tissue inhibitor of metalloproteinase (TIMP)1, TIMP2, estrogen receptor (ER)α, ERβ and apoptosis-related gene B cell lymphoma 2 (Bcl-2)-associated agonist of cell death (Bad) and Bcl-2-associated X (Bax) in the USL were analyzed. Results The protein expression and mRNA levels of MMP2 and MMP9, mRNA levels of BAD and BAX, and protein expression of active cleaved-Caspase3 were significantly higher in the POP group. There were no evident differences in COLIII, MMP1 or ERβ expression at either the mRNA or protein level or in TIMP1, TIMP2 or Caspase3 by IHC between the two groups. However, obvious decreases in COLI and ERα were evident at both the mRNA and protein levels in the POP group, and the mRNA levels of TIMP1 and TIMP2 were also decreased compared to those of the control group. Conclusion ECM in the USL tissues of POP patients is remodeled compared with non-POP patients and is characterized by decreased synthesis and increased degradation of collagen; moreover, the levels of the main proteins involved in apoptosis are increased in POP tissue.