Neurovascular alterations of muscularis propria in the human anterior vaginal wall in pelvic organ prolapse

Abstract

In the pathophysiology and progression of pelvic organ prolapse (POP), it has been demonstrated that there is a reorganisation of the muscularis propria of the anterior vaginal wall due to a phenotypic smooth muscle cell to myofibroblast switch. An abnormal deposition of collagen type III seems to be influenced by the involvement of advanced glycation end‐products. The aim of the present study was to evaluate the hypothesis that this connective tissue remodelling could also be associated with neurovascular alterations of the muscularis in women with POP compared with control patients. We examined 30 women with POP and 10 control patients treated for uterine fibromatosis. Immunohistochemical analysis, using glial fibrillary acidic protein, S‐100 protein, receptor tyrosine kinase, neurofilament and α‐smooth muscle actin antibodies, was performed. S‐100, receptor tyrosine kinase and neurofilament were also evaluated using Western blot analysis. We observed a decrease in all neurovascular‐tested markers in nerve bundles, ganglia and interstitial cells of Cajal from POP samples as compared with controls. Even if the processes responsible for these morphological alterations are still not known, it is conceivable that collagen III deposition in the anterior vaginal wall affects not only the architecture of the muscle layer but could also modify the intramuscular neurovascularisation and account for an alteration of the neuromuscular plasticity of the layer.

Single-cell transcriptome profiling of the vaginal wall in women with severe anterior vaginal prolapse

“…The enrichment of the term ECM organization and disassembly in most cell types suggested that diverse types of vaginal cells are widely involved in ECM dysregulation. In particular, the terms collagen catabolic process and collagen fibril organization were enriched in upregulated genes in smooth muscle cells from POP samples, while muscle system process was enriched in downregulated genes, implying that the phenotypic function of smooth muscle cells might switch and play a vital role in collagen metabolism when prolapse occurs, consistent with previous studies reporting that smooth muscle cells undergo an aberrant switch from a contractile to a synthetic ECM phenotype and contribute to the distensibility and fragility of the prolapsed vaginal wall 33 . Another notable finding was the enrichment of immune reaction disorders in DEGs in multiple cell types from POP samples.…”

“…Moreover, tissue remodeling-related interactions such as the TGFB1–TGFBR2 interaction were gained between smooth muscle cells and some cell types, indicating that these cells participate in ECM and tissue modeling. The phenotypic switch from smooth muscle cells to myofibroblasts could be the underlying cause of structural changes in the muscularis 33 .…”

Single-Cell Sequencing Unveils the Heterogeneity of Nonimmune Cells in Chronic Apical Periodontitis

“…MFs were also considered to be transited from smooth muscle cells according to phenotypic characteristics and structural changes in the muscularis (Sferra et al, 2019). Cells in Bs2 coexpressed smooth muscle cells and myofibroblasts, as previously suggested by their expression of MYH11, ACTG2, and DES of smooth muscle cells and TAGLN and ACTA2 of myofibroblasts.…”

Pelvic Organ Prolapse Is Associated with Osteoporosis in Korean Women: Analysis of the Health Insurance Review and Assessment Service National Patient Sample

“…However, the pathophysiology of POP is still unclear and is likely multifactorial [9]. POP is associated with the weakening of connective tissue and muscles in the pelvis and with neuromuscular dysfunction [10,11]. Insufficient collagen amount and changes in the extracellular matrix (ECM) of the pelvic floor are molecular changes that lead to the development of POP [12].…”