Transcriptomic Profiling of Cumulus Cells Reveals Dysregulated Genes and Pathways in PCOS-Related Infertility

Background: Polycystic ovarian syndrome (PCOS) is a leading cause of infertility and metabolic dysfunction in women, characterized by hyperandrogenism, anovulation, and insulin resistance. Cumulus cells play a crucial role in folliculogenesis and oocyte maturation, necessitating a deeper understanding of their molecular alterations impact in PCOS. Method: This study investigates transcriptomic differences in cumulus cells between PCOS and non-PCOS women using high-throughput RNA sequencing data obtained from the NCBI Gene Expression Omnibus (GEO) database (Accession Number: GSE277906). The RNA sequencing data from 23 PCOS and 17 non-PCOS women were analysed to identify differentially expressed genes (DEGs) using R-based computational pipelines. Results: Differential gene expression analysis identified 3,245 significantly dysregulated genes, comprising 1,723 up regulated and 1,522 downregulated genes in PCOS samples. Functional enrichment analysis revealed that key DEGs (CDH5, CLEC4D, and GNAT1) were associated with follicular development, insulin signaling, and immune response. Gene Set Enrichment Analysis (GSEA) further identified dysregulation in metabolic and reproductive pathways, including ribonucleoprotein complex biogenesis and vascular endothelial growth factor (VEGF) signaling. Conclusion: Findings from this study suggest that altered gene expression in cumulus cells may impair oocyte competence, potentially influencing fertility outcomes in PCOS patients. Additionally, the study identifies GNAT1, previously linked to diabetes, as a novel candidate in PCOS pathophysiology. Future studies should validate these findings through functional experiments and explore targeted therapeutic interventions to mitigate the reproductive consequences of PCOS.