Little is known about the pathophysiology of pelvic organ prolapse (POP). In 1996, Jackson presented a hypothesis on pelvic floor connective tissue that tried to explain the development of POP on a molecular level. The objective of this review is to test the hypothesis against recent literature. The method used was a review of literature. The association between POP and connective tissue metabolism is well established. However, the causality of this association is unclear. The characteristics of the pelvic floor connective tissue of POP patients relate to tissue repair. To resolve the question of cause and effect, the role of fibroblasts in producing the extracellular matrix should be clarified. With these data, the use of autologous or allogenic stem cells in the treatment of POP may come in sight. Recent literature supports the hypothesis of Jackson but does not resolve long-standing questions on the aetiology of POP.

The purpose of this review is to review the data on the relationship of obesity and pelvic organ prolapse (POP). This review is timely and relevant as the prevalence of obesity is increasing worldwide, and it is an important risk factor to consider in counseling women on management of prolapse symptoms and outcomes for surgical treatment. The main findings in the literature include: Obesity is increasing worldwide and impacts health, social life, work and healthcare costs. Elevated BMI is an important lifestyle factor affecting pelvic prolapse. The most probable mechanism of POP development among obese women is the increase in intra-abdominal pressure that causes weakening of pelvic floor muscles and fascia. Obesity is associated with significant pelvic floor symptoms and impairment of quality of life (QOL). Weight loss is likely not associated with anatomic improvement, but may be associated with prolapse symptom improvement. Weight loss should be considered a primary option in obese women for its beneficial effects on multiple organ systems and reducing pelvic floor disorder (PFD) symptoms. Although the operation time in obese women is significantly longer than in healthy weight women, the complication rate of surgery has not been shown to be increased compared to nonobese patients, regardless of route of surgery. There are data to support the vaginal approach in obese women. Some studies have shown that women with high body weight are associated with an increase in the risk for both anatomical and functional recurrence, and other studies have shown no difference. Obesity is a prevalent modifiable condition that impacts PFDs including pelvic prolapse. Patients should be counseled using clinical judgment, knowledge of the literature and with the goal of improving QOL.

Pelvic organ prolapse (POP) is characterised by the weakening of the pelvic floor support tissues, and often by subsequent prolapse of the bladder outside the body, i.e. cystocele. The bladder is kept in place by the anterior vaginal wall which consists of a dense extracellular matrix rich in collagen content that is maintained and remodelled by fibroblastic cells, i.e. fibroblasts and myofibroblasts. Since altered matrix production influences tissue quality, and myofibroblasts are involved in normal and pathological soft tissue repair processes, we evaluated matrix production of cells derived from pre- and post-menopausal POP and non-POP control anterior vaginal wall tissues. Results showed that cells from postmenopausal POP women deposited matrices with high percentage of collagen fibres with less anisotropic orientation and increased stiffness than those produced by controls. There was a transient increase in myofibroblastic phenotype that was lost after the peak of tissue remodelling. In conclusion, affected fibroblasts from postmenopausal prolapsed tissues produced altered matrices in vitro compared to controls. Such aberrant altered matrix production does not appear to be a consequence of abnormal phenotypical changes towards the myofibroblastic lineage.

Fibroblast to myofibroblast differentiation is a key feature of wound-healing in soft tissues, including the vagina. Vaginal fibroblasts maintain the integrity of the vaginal wall tissues, essential to keep pelvic organs in place and avoid pelvic organ prolapse (POP). The micro-environment of vaginal tissues in POP patients is stiffer and has different extracellular matrix (ECM) composition than healthy vaginal tissues. In this study, we employed a series of matrices with known stiffnesses, as well as vaginal ECMs, in combination with vaginal fibroblasts from POP and healthy tissues to investigate how matrix stiffness and composition regulate myofibroblast differentiation in vaginal fibroblasts. Stiffness was positively correlated to production of α-smooth muscle actin (α-SMA). Vaginal ECMs induced myofibroblast differentiation as both α-SMA and collagen gene expressions were increased. This differentiation was more pronounced in cells seeded on POP-ECMs that were stiffer than those derived from healthy tissues and had higher collagen and elastin protein content. We showed that stiffness and ECM content regulate vaginal myofibroblast differentiation. We provide preliminary evidence that vaginal fibroblasts might recognize POP-ECMs as scar tissues that need to be remodeled. This is fundamentally important for tissue repair, and provides a rational basis for POP disease modelling and therapeutic innovations in vaginal reconstruction.