A Systematic Review and Integrated Bioinformatic Analysis on the Gene Expression of Cumulus-Oocyte Complex Following...

Infertility, a rising global concern, is frequently caused by genetic causes, making modern reproductive methods like in vitro fertilisation (IVF) and in vitro maturation (IVM) necessary for successful conception. Nonetheless, little is known about the molecular pathways causing infertility. This study conducted a systematic review following PRISMA guidelines, aiming to comprehensively elucidate the gene expression profiles of cumulus cells following IVM and their implications for reproductive outcomes. A thorough literature search was conducted across multiple databases, employing a combination of keywords related to cumulus cells, IVM, and gene expression. For this systematic review, screening processes identified four clinical human studies meeting inclusion criteria, published between 2013 and 2022. The studies used qPCR and RNA sequencing to compare gene expression in cumulus cells pre- and post-IVM or between IVF and IVM patients. Despite variations in sample sizes and methodologies, 22 differentially expressed genes (DEGs) were identified, with 10 common DEGs between IVF and IVM matured cumulus-oocyte complexes. Protein-protein interaction network analysis revealed a complex molecular network associated with cumulus cell function and oocyte maturation. Clustering analysis identified a significant cluster enriched in genes involved in the epidermal growth factor receptor signalling pathway and cell membrane dynamics. Gene ontology and pathway enrichment analysis highlighted the involvement of DEGs in cell-cell signalling, signal transduction, and ovarian steroidogenesis pathways. The findings emphasise the importance of understanding molecular mechanisms in infertility and provide valuable insights for optimising assisted reproductive technologies. Future research should focus on validating these findings and exploring potential therapeutic targets for improving reproductive outcomes.