Gene Expression Profiling of Cumulus-oocyte Complex in Infertile Women: A Systematic Review and Integrated Bioinformatic Analysis

The cumulus-oocyte complex (COC) is an important complex for oocyte maturation. Gene expression in the cumulus cells surrounding the oocyte is crucial for regulating maturation. Abnormal gene expression in the cumulus-oocyte complex may inhibit oocyte maturation and subsequently lead to infertility. A thorough understanding of impacted gene expression profiles and molecular pathways in infertile women is necessary. However, the gene expression profiles vary between studies. Thus, a comprehensive literature search across EBSCOhost, PubMed, ScienceDirect, and Scopus databases was conducted to robustly identify gene expression profiles of cumulus-oocyte complexes and the molecular pathways involved in infertility development. Terms including (“Infertile women” OR Sterility OR Subfertility OR Infertility OR “Sub-fertility”) AND (“Gene expression” OR Profiling OR Transcriptome) AND (“In-vitro fertilization” OR “In-vitro fertilisation” OR IVF) were used as keywords in all fields. 2090 studies were retrieved, and all were screened against the inclusion and exclusion criteria. After the screening, five studies were selected, and 897 differentially expressed genes (DEGs) were identified across them. The integrated bioinformatic analysis using DAVID, STRING, and Cytoscape revealed a protein-protein interaction (PPI) network comprising 30 high-intermolecular-interaction clusters. Based on Gene Ontology (GO) annotations, most DEGs are expressed in the extracellular space, cytosol, and mitochondria. Correspondingly, the DEGs were identified as modulating communication with the extracellular environment via signalling pathways and regulating proliferation via DNA transcription and the cell cycle. This systematic review further elucidates the genes and molecular mechanisms within the cumulus-oocyte complex involved in the development of infertility.