ABSTRACT
Pelvic organ prolapse (POP) is a debilitating condition of unknown aetiology affecting > 50% of women over 40 years of age. In POP patients, the vaginal walls are weakened allowing descent of pelvic organs through the vagina. We sought to determine if sphingosine-1-phosphate (S1P) signalling, which regulates smooth muscle contractility and apoptosis via the RhoA/Rho-kinase (ROK) pathway, is altered in the vagina of women with POP. Utilising anterior vaginal wall specimens, we provide novel demonstration of the S1P pathway in this organ. Additionally, comparing specimens from women having pelvic reconstructive surgery for POP and control subjects, we reveal increases in mRNA expression of the three major mammalian S1P receptors (S1P1-S1P3), and RhoA and the ROK isoforms: ROKα and ROKß in POP patients, which correlates with a decrease in elastic fibre assembly pathway constituents. Taken together, our data suggest the S1P/ROK pathway as a novel area for future POP research and potential therapeutic development.
Subject(s)
Lysophospholipids/metabolism , Pelvic Organ Prolapse/metabolism , RNA, Messenger/metabolism , Sphingosine/analogs & derivatives , Vagina/metabolism , rho-Associated Kinases/metabolism , Adult , Aged , Case-Control Studies , Female , Humans , Isoenzymes , Middle Aged , Pelvic Organ Prolapse/genetics , Receptors, Lysosphingolipid/genetics , Signal Transduction , Sphingosine/metabolism , Sphingosine-1-Phosphate Receptors , rho-Associated Kinases/genetics , rhoA GTP-Binding Protein/geneticsABSTRACT
Interstitial cystitis is a clinical condition occurring predominantly in women and is characterized by urinary frequency, urgency, and pain. Patient symptoms have the potential to significantly affect quality of life, posing a challenge to some to perform activities of daily living. This article comprehensively reviews the literature on the epidemiology, etiology, evaluation, and treatment of interstitial cystitis, and considers commonly associated pelvic floor dysfunction.
