Microarray analysis of gene expression profiles in pelvic organ prolapse

Abstract

To identify the differentially expressed genes in cardinal ligament between patients with pelvic organ prolapse (POP) and postmenopausal women without POP by Human Genome Expression Chip and explore the potential molecular mechanism involved in POP. From January to May, 2007, cardinal ligament samples were obtained from 3 postmenopausal patients with POP-Q stage III and 3 postmenopausal patients underwent hysterectomy due to other benign gynecologic diseases without POP in Peking Union Medical College Hospital. HE and Masson's trichrome staining was used to verify tissue origin and inspect histological changes. Those differentially expressed genes in cardinal ligaments were identified by Human Genome Chip and further interrogated with Gene Ontology (GO) and Pathway Analysis. Those remarkable expressed genes were confirmed by qRT-PCR. Alterations of ligament architecture in POP patients included disarrangement and collapse of smooth muscle bundles and collagen fibers. A total of 179 differentially expressed genes were screened between POP and non-POP cardinal ligament tissue, including 20 functional unknown genes. A total of 107 genes were upregulated in POP group, while 72 genes downregulated. Those differentially genes were revealed associated with multiple functional proteins and metabolic pathways by biological analysis. Among these, Wnt signaling pathway exhibited the most remarkable changes. Real-time quantitative PCR showed the genes of COL1A1, DKK1, SFRP1, FZD5, WNT16b in POP group (2.98+/-1.40, 3.03+/-0.48, 8.13+/-4.42, 5.19+/-3.50, 12.40+/-3.88) were upregulated significantly compared with non-POP group (1.09+/-0.08, 1.20+/-0.18, 0.41+/-0.51, 0.87+/-0.24, 1.40+/-0.47; P<0.05). The pathophysiology of POP is complex and associated with multiple functional proteins and metabolic pathways. Among these, the antagonist DKK1, SFRP1 in Wnt signaling pathway may contribute to a neurodegenerative role in POP development.