Exploring key genes related to air pollutants in polycystic ovary syndrome: A comprehensive analysis from transcriptome and single-cell analysis combined with network toxicology

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age, and emerging evidence links air pollutants to its development. METHODS: We integrated bulk and single-cell RNA-seq data with air pollutant-associated molecular targets to identify candidate genes, using differential expression, machine learning, functional enrichment, and molecular docking analyses. RESULTS: ESR2, FAAH, and MAOB were consistently upregulated in PCOS and associated with lysosome, spliceosome, and cell cycle pathways. Docking simulations suggested strong interactions between MAOB/ESR2 and toluene. Single-cell analysis indicated granulosa cells and fibroblasts as major affected populations, with gene expression varying across differentiation stages. CONCLUSION: This study provides the integrative transcriptomic analysis linking air pollutant exposure to PCOS. ESR2, FAAH, and MAOB emerge as potential mediators of pollutant-induced endocrine disruption, offering novel molecular insights and candidate biomarkers for environmentally driven PCOS.