Original Article
Identifying distinct nanoscopic features of native collagen fibrils towards early diagnosis of pelvic organ prolapse

https://doi.org/10.1016/j.nano.2015.11.006Get rights and content

Abstract

Pelvic organ prolapse (POP) is characterized by weakening of the connective tissues and loss of support for the pelvic organs. Collagen is the predominant, load-bearing protein within pelvic floor connective tissues. In this study, we examined the nanoscopic structures and biomechanics of native collagen fibrils in surgical, vaginal wall connective tissues from healthy women and POP patients. Compared to controls, collagen fibrils in POP samples were bulkier, more uneven in width and stiffer with aberrant D-period. Additionally, the ratio of collagen I (COLI) and collagen III (COLIII) is doubled in POP with a concomitant reduction of the amount of total collagen. Thus, POP is characterized by abnormal biochemical composition and biophysical characteristics of collagen fibrils that form a loose and fragile fiber network accountable for the weak load-bearing capability. The study identifies nanoscale alterations in collagen as diagnostic markers that could enable pre-symptomatic or early diagnosis of POP.

From the Clinical Editor

Pelvic organ prolapse (POP) occurs due to abnormalities of the supporting connective tissues. The underlying alterations of collagen fibers in the connective tissues have not been studied extensively. In this article, the authors showed that collagen fibrils in POP patients were much different from normal controls. The findings may provide a framework for the diagnosis of other connective diseases.

Graphical abstract

In this study, nanoscopic structures and biomechanics of native collagen fibrils in surgical, vaginal wall connective tissues from healthy women and pelvic organ prolapse (POP) patients have been examined to identify nanoscale alterations in collagen as potential diagnostic markers for POP.

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Section snippets

Handling of clinical tissue samples

Vaginal wall connective tissues from four healthy pre-menopausal (pre-M) women (ages 25-41), five healthy post-menopausal (post-M) women (ages 58-73), and five POP women (post-M, ages 51-73) were obtained with their consent following the approved IRB protocols at Rush University Medical Center (ORA # 08081108) and University of Illinois at Chicago (IRB protocol #2011-1025). After the blood was removed from the biopsy sample, the bulk tissue piece was cooled to 0Ā Ā°C, and sequentially sectioned by

Nanoscopic structures of native collagen fibrils in fresh tissues

FigureĀ 2 shows the AFM images revealing the apparent morphological differences in collagen fibrils from tissues of both post-M and POP women with respect to those of pre-M women. At the nanoscopic scale, pre-M collagen fibrils are densely packed and uniformly aligned with respect to each other (FigureĀ 2, A). These fibrils bundle into collagen fibers that form the fiber network visible in Gomori staining and immunofluorescent images. It is apparent from the micrometer scale images that these

Discussion

POP is often correlated to changes in the amount, assembly, degradation and aging of collagen in the extracellular matrix of pelvic floor connective tissues.13, 35 In the current study, we identify such changes in situ at the microscopic and nanoscopic scales to derive their direct correlations underlying the biomechanical failure in POP. We have discovered that the POP collagen fibrils are thicker, stiffer, more uneven, and characterized by a small but significant decrease in D-period. Changes

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    None of the authors declare a conflict of interest and commercial interest related to this work.

    This work was supported by the Deutsch Family Foundation for Women's Health. Funding was also supplied by a development grant from the Department of Obstetrics and Gynecology at University of Illinois, Chicago and a grant from DARPA (W911NF-09-1-0378) to JDS.

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