Oxidative status of cardinal ligament in pelvic organ prolapse

Abstract

Pelvic organ prolapse (POP) is a common and distressing health problem in adult women, but the pathophysiological mechanism is yet to be fully elucidated. Previous studies have indicated that oxidative stress may be associated with POP. Thus, the aim of the present study was to investigate the oxidative status of pelvic supportive tissue in POP and further demonstrate that oxidative stress is associated with the pathogenesis of POP. A total of 60 samples were collected from females undergoing hysterectomy for POP or cervical intraepithelial neoplasia (CIN). This included 16 females with POP II, 24 females with POP III–IV (according to the POP-Q system) and 20 females with CIN II–III as the control group. Immunohistochemistry was utilized to measure the expression of oxidative biomarkers, 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxynonenal (4-HNE). Major antioxidative enzymes, mitochondrial superoxide dismutase (MnSOD) and glutathione peroxidase 1 (GPx1) were measured through reverse transcription-quantitative polymerase chain reaction, western blotting and enzyme activity assays. The results demonstrated that in the cardinal ligament, the expression of 8-OHdG and 4-HNE was higher in the POP III–IV group compared with the POP II group and control group. The MnSOD and GPx1 protein level and enzyme activity were lower in the POP III–IV group compared with the POP II or the control group, while the mRNA expression level of MnSOD and GPx1 was increased. In conclusion, oxidative damage is increased in the pelvic supportive ligament of female patients with POP and the antioxidative defense capacity is decreased. These results support previous findings that oxidative stress is involved in the pathogenesis of POP.

Advances in molecular mechanisms of pelvic organ prolapse (Review)

“…A further study concluded that mechanical strain may activate the PI3K/AKT-mediated OS signaling pathway, thereby promoting the apoptosis and senescence of pelvic fibroblasts, and reducing the production of collagen (36). A subsequent study also confirmed this notion (37). Furthermore, reduced OS has been indicated to promote collagen synthesis, while its overexpression may interfere with the homeostasis and metabolism of ECM by affecting the levels of MMPs/TIMPs and the activation of the TGF-β1/Smad signaling pathway, which in turn results in induction of POP (38).…”

Advanced glycation end products (AGEs) downregulate the miR-4429/PTEN axis to promote apoptosis of fibroblasts in pelvic organ prolapse

“…Apart from the hyperglycemic environment, the formation process of AGEs also accelerates under chronic inflammation or oxidative stress conditions (31,32). Previous studies have reported that ROS increase in POP (33,34), interfering with multiple cellular processes and favoring POP development. Thus, we speculate that the high level of AGEs in the prolapse tissues could result from increased ROS in POP because the formation of AGEs accelerates under the elevated ROS level in prolapse tissues (35).…”

COL3A1 rs1800255 polymorphism is associated with pelvic organ prolapse susceptibility in Caucasian individuals: Evidence from a meta-analysis

“…Pelvic organ prolapse (POP) is a phenomenon that pelvic organs such as uterus, vagina, bowel and bladder leave out of their normal anatomical location, resulting in a serious of functional disorders [ 1 ]. It is a very frequent disease in postmenopausal women, especially in senile females [ 2 ].…”