Molecular Characteristics of the Endometrium in Polycystic Ovary Syndrome with Insulin Resistance

Polycystic ovary syndrome (PCOS), one of the most common endocrine and reproductive disorders in women of reproductive age, is frequently complicated by insulin resistance (IR), which affects 50%–80% of PCOS patients and is strongly associated with an increased risk of early pregnancy loss. Evidence suggests that IR may contribute to this risk by impairing endometrial function, a notion supported by observed functional improvements following metformin treatment. While previous studies have provided clues regarding PCOS with IR (PCOS-IR) at the ovarian miRNA and endometrial protein levels, the understanding of the upstream transcriptomic events regulating these pathways remains limited. We performed RNA-Seq on endometrial tissues from PCOS-IR and PCOS without IR (PCOS-NIR), thereby identifying 339 common differentially expressed genes (DEGs) using DESeq2 and Limma. Functional enrichment analysis revealed that DESeq2-identified genes primarily participated in cellular signaling, metabolic regulation, and immune-related pathways. Further weighted gene co-expression network analysis (WGCNA) identified gene modules highly correlated with the PCOS-IR phenotype. Integrating multi-step strategies, including random forest analysis and STRING interaction networks, ultimately identified FGF17, AKT3, and IRS4 as key candidate genes. Quantitative real-time PCR (qRT-PCR) confirmed that FGF17 mRNA expression was significantly downregulated in the endometrium of the PCOS-IR group. This finding suggests that FGF17 may play a pivotal role in PCOS-IR-related endometrial dysfunction, with promise as a therapeutic target to improve reproductive outcomes in patients. These results provide important theoretical support for subsequent mechanistic exploration and clinical intervention.