Mechanobiological Dysregulation of Fibroblasts and Extracellular Matrix Failure in Pelvic Organ Prolapse

Pelvic organ prolapse (POP) is increasingly recognized as a disorder of pelvic connective tissue mechanobiology. Fibroblasts maintain extracellular matrix (ECM) homeostasis, but their dysfunction is a hallmark of POP. However, their role as mechanosensitive regulators remains incompletely understood. This narrative review summarizes current evidence on fibroblast mechanobiology and ECM remodeling in POP and synthesizes these findings into a potential multiscale framework linking mechanical loading to maladaptive tissue remodeling and prolapse progression.

We conducted a narrative review on fibroblast mechanobiology and ECM failure in POP. A PubMed search up to February 2026 identified 882 records; 877 were screened after duplicate removal, and 64 PubMed-indexed articles were included, supplemented by reference-list screening. No formal systematic review protocol or PRISMA flow diagram was applied.

Accumulating evidence indicates that POP is not merely an age-related degenerative condition but may involve impaired force transmission within pelvic connective tissues. Sustained mechanical overload disrupts the actin cytoskeleton and focal adhesion stability in fibroblasts, aberrantly activating mechanosensitive pathways such as TGF-β/Smad and RhoA/ROCK signaling. These signaling alterations promote fibroblast apoptosis, cellular senescence, or pathological myofibroblast differentiation, contributing to collagen type I/III imbalance, increased matrix degradation, and impaired collagen cross-linking. Based on these findings, we propose a multiscale mechanobiological framework linking abnormal mechanical loading, fibroblast dysfunction, ECM disorganization, and progressive pelvic support failure.

Dysregulated fibroblast mechanobiology may contribute to POP pathogenesis. Integrating tissue biomechanics, cellular mechanotransduction, and ECM remodeling may inform early intervention strategies and biomechanically targeted therapies.