Gene and non-coding RNA expression in human cumulus cells in polycystic ovary syndrome: A systematic review
Abstract
OBJECTIVE: This systematic review aimed to synthesize and critically appraise human studies on coding and non-coding RNA expression in cumulus cells (CCs) from women with Polycystic Ovary Syndrome (PCOS), to map consistently dysregulated pathways, evaluate links to oocyte competence, and identify key methodological limitations.
METHODS: A systematic search of five electronic databases (MEDLINE/PubMed, Embase, Web of Science, Scopus, Cochrane CENTRAL) was conducted from inception to October 25, 2025. Peer-reviewed human studies comparing CC RNA expression in PCOS versus controls, with explicit cumulus isolation and primary RNA data, were included. Study selection, quality assessment, and data extraction followed pre-defined analytic prisms focusing on cell-type specificity, oocyte maturation stage, stimulation protocol, and clinical phenotype. A qualitative synthesis was performed due to substantial clinical and methodological heterogeneity.
RESULTS: Thirty-three studies were included. The CC transcriptome in PCOS is characterized by a coherent phenotype: pathway-level enrichment of EGFR-MAPK and PI3K-AKT/insulin signaling, an imbalanced TGF-β/oocyte-somatic cell axis, and blunted induction of cumulus expansion/extracellular matrix (ECM) genes (e.g., TNFAIP6, PTX3). Non-coding RNA profiles (miRNAs, lncRNAs, circRNAs) corroborate these findings, targeting the same pathways. These signatures are strongly modified by oocyte maturation stage (largest differences at Germinal…
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