Department of Chemistry, Illinois Institute of Technology, Chicago, IL, United States.
Department of Urogynecology, NorthShore Medical Group, Skokie, IL, United States; Department of Obstetrics and Gynecology, Irving Medical Center, Columbia University, New York, NY, United States.
Acta Biomater. 2022 Oct 15;152:335-344. doi: 10.1016/j.actbio.2022.08.059. Epub 2022 Aug 31.
Collagen is the predominant structural protein within connective tissues. Pelvic organ prolapse (POP) is characterized by weakening of the pelvic floor connective tissues and loss of support for pelvic organs. In this study, we examined the multiscale structure, molecular composition and biomechanics of native collagen fibrils in connective tissues of the posterior vaginal fornix collected from healthy women and POP patients, and established the correlation of these properties with clinical POP quantification (POP-Q) scores. The collagen characteristics, including collagen amount, ratio of Collagen I and Collagen III, collagen fibril d-period, alignment and stiffness, were found to change progressively with the increase of the clinical measurement of Point C, a measure of uterine descent and apical prolapse. The results imply that a severe prolapse is associated with stiffer collagen fibrils, reduced collagen d-period, increased fibril alignment and imbalanced collagen synthesis, degradation and deposition. Additionally, prolapse progression appears to be synchronized with deterioration of the collagen matrix, suggesting that a POP-Q score obtained via a non-invasive clinical test can be potentially used to quantitatively assess collagen abnormality of a patient's local tissue. STATEMENT OF SIGNIFICANCE: Abnormal collagen metabolism and deposition are known to associate with connective tissue disorders, such as pelvic organ prolapse. Quantitative correlation of the biochemical and biophysical characteristics of collagen in a prolapse patient's tissue with the clinical diagnostic measurements is unexplored and unestablished. This study fills the knowledge gap between clinical prolapse quantification and the individual's cellular and molecular disorders leading to connective tissue failure, thus, provides the basis for clinicians to employ personalized treatment that can best manage the patient's condition and to alert pre-symptomatic patients for early management to avoid unwanted surgery.
胶原是结缔组织中主要的结构蛋白。盆腔器官脱垂（POP）的特征是盆底结缔组织变弱以及盆腔器官失去支撑。在这项研究中，我们检查了来自健康女性和 POP 患者的阴道后穹窿结缔组织中天然胶原原纤维的多尺度结构、分子组成和生物力学特性，并建立了这些特性与临床 POP 定量（POP-Q）评分的相关性。胶原特性，包括胶原量、胶原 I 和胶原 III 的比例、胶原纤维 d-周期、排列和刚度，随着临床测量点 C 的增加而逐渐变化，点 C 是衡量子宫下降和顶端脱垂的指标。结果表明，严重脱垂与胶原纤维更硬、胶原 d-周期缩短、纤维排列增加以及胶原合成、降解和沉积失衡有关。此外，脱垂进展似乎与胶原基质的恶化同步，这表明通过非侵入性临床测试获得的 POP-Q 评分可潜在用于定量评估患者局部组织的胶原异常。意义陈述：已知异常的胶原代谢和沉积与结缔组织疾病有关，例如盆腔器官脱垂。在脱垂患者组织中胶原的生化和物理特性与临床诊断测量值之间的定量相关性尚未得到探索和确立。这项研究填补了临床脱垂定量与导致结缔组织衰竭的个体细胞和分子紊乱之间的知识空白，为临床医生提供了个性化治疗的依据，以便最好地管理患者的病情，并提醒有症状前的患者进行早期管理，以避免不必要的手术。
