Research Paper Volume 13, Issue 24 pp 25886—25902
Structural, functional and molecular pathogenesis of pelvic organ prolapse in patient and Loxl1 deficient mice
- 1 Clinical Research Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China
- 2 Dr. Li Dak Sum and Yip Yio Chin Center for Stem Cells and Regenerative Medicine, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China
- 3 Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province, Zhejiang University, Hangzhou, Zhejiang 310003, PR China
- 4 Department of Gynaecology, The Fourth Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China
- 5 Department of Gynaecology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, PR China
Received: October 12, 2020 Accepted: November 11, 2021 Published: December 19, 2021
https://doi.org/10.18632/aging.203777How to Cite
Copyright: © 2021 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Pelvic organ prolapse is a worldwide health problem to elderly women. Understanding its pathogenesis and an ideal animal model are crucial to developing promising treatments. The present study aimed to investigate new clinical significance and detailed mechanism of pelvic organ prolapse by comparing the structural, functional and molecular dysfunctions of pelvic organ prolapse in patient and Loxl1 deficient mice. Our results showed that human vagina tissues from prolapsed site showed disarranged collagen and elastic fibers compared with the non-prolapse tissue. A gene ontology (GO) analysis of differentially expressed genes revealed molecular changes mainly related to inflammatory response and extracellular matrix (ECM) organization. While the mice lacking Loxl1 developed stable POP phenotype and disordered ECM structure in histology. Such Loxl1 knockout mice exhibited a significantly urinary dysfunction and decreased mechanical properties of the pelvic floor tissues, implying that POP in human condition might be induced by progressively decreased mechanics of pelvic tissues following ECM catabolism. Similarly, we not only identified significant up-regulated ECM catabolism processes and down-regulated ECM synthesis processes, but also characterized high level of inflammatory response in vagina tissue of the Loxl1 deficient mice. Thus, all these pathological changes in the POP mice model was consistent with those of the clinical elderly patients. These findings provide new insight into remodeling of POP by LOXL1 regulation and be of great importance to develop combination treatments of ECM metabolism and inflammation regulation strategy.