Multi-omics analysis reveals synergistic interplay of metabolic dysregulation, oxidative stress, and inflammation in polycystic ovary syndrome

作者：Qihong Chen, Xuewei Li, Weiming Zhou, Jiawei Xiao, Yue Yang, Hanxue Chen, Qi-zhi Luo, Fanliang Meng, Bo-Feng Zhu, Xuncai Chen · 发表于：Biomedical Analysis · 年份：2025 · DOI：10.1016/j.bioana.2025.06.002 · 被引用次数：10 · 研究领域：Ovarian function and disorders、Reproductive Biology and Fertility、Lipid metabolism and disorders

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine and metabolic disorder characterized by hormonal imbalances, metabolic dysfunction, and chronic inflammation. To elucidate the molecular mechanisms underlying PCOS pathogenesis, this study employed an integrated multi-omics approach, combining serum metabolomic and proteomic analyses of clinically diagnosed PCOS patients and healthy controls. The findings revealed three key synergistic pathways contributing to disease progression: (1) dysregulation of the sex hormone - uric acid axis and altered polyunsaturated fatty acid (PUFA) metabolism; (2) oxidative stress-induced NAD + depletion, driven by xanthine oxidase (XO) overactivity and aberrant MAPK/HSP/GSTP1 signaling; and (3) disturbances in lipid metabolism that trigger activation of the arachidonic acid - cyclooxygenase (COX)/prostaglandin inflammatory cascade. These interconnected molecular networks establish a pathological cycle characterized by hyperandrogenism, oxidative stress, and sustained inflammation, ultimately resulting in anovulation and morphological alterations of the ovaries. This study provides novel mechanistic insights into the molecular crosstalk governing PCOS and identifies potential therapeutic targets, including the XO/NAD + redox axis and the arachidonic acid - COX inflammatory pathway. The systems biology framework presented here offers a foundation for developing personalized intervention strategies tailored to the heterogeneous phenoty...