Genome-based expression profiles study for the pathogenesis of pelvic organ prolapse: An array of 33 genes model

摘要

Introduction and hypothesis: To explore the potential molecular mechanisms contributing to the pathogenesis of pelvic organ prolapse (POP) with the aid of high-density oligonucleotide microarrays. Methods: We compared microarray gene expression profiles in pelvic connective tissue from women with POP and nonprolapse controls. The round ligament and uterosacral ligament tissues were removed from each subject at the time of laparoscopic hysterectomy. RNA was then extracted, and all labeled samples were hybridized to ABI Human Genome Survey Microarray version 2.0 (Applied Biosystems, CA, USA). Results: The Mahalanobis distance in hierarchical cluster analysis revealed a model of 33 genes, which contained high expressions of round and uterosacral ligaments from women with POP. According to gene ontology, the expressions of mitochondrial genes encoding ribosomal protein were upregulated. Genes involved in potential interactions with mitochondrial electron transport, nucleosome assembly, cell cycle, and apoptosis were also upregulated. As a result, defective mitochondrial translation caused by ribosomal protein contributes to the potential molecular etiology of POP. Such changes, jointly termed "remodeling of pelvic connective tissue", can constitute an important long-term consequence of POP. Conclusions: Our results support the use of genome-based expression profiling as a commonplace platform for diagnostic tests of POP.