Advances in molecular mechanisms of pelvic organ prolapse (Review)

Abstract

Pelvic organ prolapse (POP) is a common gynecological benign disease occurring in middle-aged and elderly females. Its incidence increases every year. To date, the majority of studies investigating its etiology have not evaluated the underlying molecular mechanisms, which has caused substantial difficulties in the prevention, treatment and prognosis of POP. In the present narrative review, recent research studies concerning the molecular mechanisms of POP were systematically reviewed and the advances were summarized. The association between the incidence of POP and the reduction of the extracellular matrix, activation of oxidative stress, genetic susceptibility, denervation of the pelvic floor and reduction of estrogen infiltration were explored. POP is mainly associated with damage of pelvic floor muscles and connective tissue, which are directly caused by pregnancy and vaginal delivery. The majority of the molecular and genetic mutations associated with POP involve specific components of connective tissue synthesis and degradation. It is likely that macroscopic parameters, such as anatomy, lifestyle and reproductive factors, interact with microscopic parameters, such as physiology and genetics in the female pelvic floor, leading to POP. Additional research studies investigating the molecular mechanisms of POP should be performed, since they may aid public health strategies. In the present narrative review, a summary of these molecular mechanisms underlying the development of POP is provided. This included the relevant proteins and genes involved. On this basis, countermeasures were proposed. Contents

Construction of a focal adhesion signaling pathway-related ceRNA network in pelvic organ prolapse by transcriptome analysis

“…POP is primarily characterized by the weakening of support tissue and can be caused by pelvic floor connective tissue extracellular matrix remodeling, activation of oxidative stress, genetic susceptibility, denervation of pelvic floor innervation, and reduced estrogen infiltration ( Deng et al, 2021 ), however, the underlying mechanism, including the vital molecules and signaling pathways, is unknown. Furthermore, the role of regulatory ncRNAs in the pathogenesis of POP remains unclear.…”

“…Therefore, changes in the extracellular matrix play an important role in the regulation of cell adhesion, proliferation, migration, and apoptosis through mechanical signal transduction ( Fiorentino et al, 2022 ). It is well known that remodeling of the ECM in the pelvic floor connective tissue is one of the reasons for the occurrence of POP ( Deng et al, 2021 ), particularly the proportions of collagen Ⅰ and Ⅲ ( Deprest et al, 2022 ). Ruiz-Zapata et al (2016) demonstrated that matrices increase stiffness in postmenopausal women with POP compared with controls.…”

“…Prolonged stretching and mechanical stress cause progressive deterioration of the pelvic organ support ( Deng et al, 2021 ). Four mechanoresponsive genes are responsible for the regulation of actin cytoskeleton remodeling in fibroblasts under stretching, and investigations of the cytoskeleton phenotype in POP samples revealed an abnormal F-actin configuration ( Ewies et al, 2008 ; Wang et al, 2015 ).…”

Compression Optical Coherence Elastography for Assessing Elasticity of the Vaginal Wall under Prolapse after Neodymium Laser Treatment

“…The use of C-OCE to assess the absolute stiffness values of the vaginal wall in prolapse may have high potential due to objective elasticity changes of the vaginal connective tissue. It is known that the predominant pathogenetic mechanism of POP is the decreased synthesis and the increased breakdown of the extracellular matrix in the connective tissue of the pelvic floor, with collagen being its main component [75]. Numerous mechanisms are responsible for the disruption in the balanced collagen metabolism.…”

The protective effect of 17 β-estradiol on human uterosacral ligament fibroblasts from postmenopausal women with pelvic organ prolapse

“…Frontiers in Physiology frontiersin.org 06 Discussion POP is not life-threatening but has a significant impact on a patient's quality of life with its incidence increasing every year. It is well accepted that POP is associated with postmenopausal estrogen deficiency and overstretching of the pelvic floor lead by vaginal delivery (Deng et al, 2021). The current study found that overall growth rate of POP fibroblasts was significantly slower Frontiers in Physiology frontiersin.org than controls under culture conditions, and estrogen slightly increased cell proliferation of all the fibroblasts with the most prominent effect at physiological concentrations (10 −10 and 10 −9 M), and the enhancement was only observed at 24 h, perhaps because of the half-life of estrogen is about 24 h in the culture medium.…”