Yang Zhandong, Cai Xuzi, Xu Xiaoxia, Xu Zengmei, Ye Simin, Wang Yan, Hong Yanjun, Shen Baochun, Liao Qiongfeng, Xie Zhiyong, Wang Xuefeng
School of Pharmaceutical Sciences (Shenzhen), Sun Yat-Sen University, Guangzhou, 510006, China; School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Southern Medical University, Guangzhou, 510000, China.
Anal Biochem. 2022 Jun 15;647:114665. doi: 10.1016/j.ab.2022.114665. Epub 2022 Mar 23.
Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder. Nevertheless, its accurate mechanisms remain unclear. Metabolomics is a powerful technique to identify small molecules that could be used to discover pathogenesis and therapeutical targets of disease. In the present study, a urinary untargeted metabolomics combined with targeted quantification analysis was performed to uncover metabolic disturbance associated with PCOS. A total of thirty-eight metabolites were obtained between PCOS patients and healthy controls, which were mainly involved in lipids (39.5%), organic acids and derivatives (23.7%), and organic oxygen compounds (18.4%). Based on enrichment analysis, fourteen metabolic pathways were found to be perturbed in PCOS, particularly glycerophospholipid metabolism and tryptophan metabolism. Targeted quantification profiling of tryptophan metabolism demonstrated that seven compounds (tryptophan, kynurenine, kynurenic acid, quinolinic acid, xanthurenic acid, 3-hydroxyanthranilic acid and 3-hydroxykynurenine) were up-regulated in PCOS. And these tryptophan-kynurenine metabolites showed significant correlations with PCOS clinical features, such as positively associated with testosterone, free androgen index, and the ratio of luteinizing hormone to follicle stimulating hormone. Thus, this study disclosed urinary metabolome changes associated with PCOS, and might provide new insights into PCOS pathogenesis elucidation and therapeutical target development.
多囊卵巢综合征（PCOS）是一种常见的内分泌和代谢紊乱疾病。然而，其确切机制仍不清楚。代谢组学是一种强大的技术，可用于识别小分子，从而发现疾病的发病机制和治疗靶点。在本研究中，进行了一项尿液非靶向代谢组学结合靶向定量分析，以揭示与PCOS相关的代谢紊乱。PCOS患者和健康对照之间共获得了38种代谢物，主要涉及脂质（39.5%）、有机酸及其衍生物（23.7%）和有机氧化合物（18.4%）。基于富集分析，发现PCOS中有14条代谢途径受到干扰，尤其是甘油磷脂代谢和色氨酸代谢。色氨酸代谢的靶向定量分析表明，PCOS中有7种化合物（色氨酸、犬尿氨酸、犬尿酸、喹啉酸、黄尿酸、3-羟基邻氨基苯甲酸和3-羟基犬尿氨酸）上调。并且这些色氨酸-犬尿氨酸代谢物与PCOS临床特征显著相关，如与睾酮、游离雄激素指数以及黄体生成素与卵泡刺激素的比值呈正相关。因此，本研究揭示了与PCOS相关的尿液代谢组变化，并可能为阐明PCOS发病机制和开发治疗靶点提供新的见解。
