Network Analysis Suggests Ovarian Insulin Hypersensitivity Contributes to Depressed Viability of Ovarian Cells in PCOS Women

Purpose: Polycystic ovarian syndrome (PCOS) is a global health-threatening endocrinopathy that causes infertility in women. Although peripheral insulin resistance has been implicated as a risk factor of PCOS, its pathological mechanism is still merely elucidated. Aiming to systematically explore the molecular basis of PCOS, we conducted a network analysis on gene expression profiles of ovary from PCOS women. Methods: Ovarian gene expression profiles of PCOS women were collected by searching keywords of “PCOS and human” in GEO database.Then differentially expressed genes (DEGs) were identified by using Rankprod algorithm.Their primary functions were investigated by enrichment analysis based on KEGG and Gene Ontology.A core gene regulatory network in ovary of PCOS women was constructed as well, in which a significant role of the insulin signaling pathway in development of PCOS was highlighted. Result: 269 up-regulated genes and 249 down-regulated ones (pfp < 0.05) were identified in ovary of PCOS patients.A PCOS ovarian gene regulatory network was constructed based on the above. By searching hub modules in this network, signaling process guided by two hub genes insulin receptor(INSR)and insulin receptor substrate 1(IRS1)was highlighted, which were elevated in PCOS subjects. Conclusions: By integrating ovarian gene expression profiles, our network analysis revealed a significant role of insulin signaling pathway in Pathophysiology of PCOS. The elevated INSR and IRS1 would be a potential clue for insulin hypersensitivity in PCOS ovary, thereby inducing ovarian dysfunction by impairing the viability of granulosa cells.