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.
Wang et al. (Mon,) studied this question.