Obstetrics and Gynecology Department, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Endocrinol (Lausanne). 2023 Feb 24;14:1077604. doi: 10.3389/fendo.2023.1077604. eCollection 2023.
Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with a metabolic disorder. Studies have demonstrated that the malfunction of adipose tissue, particularly abdominal adipose tissue, could exacerbate reproductive and metabolic problems in PCOS patients. Adipose tissue-secreted signaling mediators (e.g., lipids and metabolites) would then interact with other body organs, including the ovary, to maintain the systemic equilibrium.
In this study, we examined adipose samples from PCOS patients and unaffected individuals using a liquid chromatography-mass spectrometry-based metabonomics approach (LC-MS/MS). PCOS biomarkers were selected using multivariate statistical analysis.
Our pathway analysis revealed that these differential metabolites could be engaged in inflammatory diseases and mitochondrial beta-oxidation. We further developed an in vitro PCOS cell model to examine the effects of hyperandrogenism on granulosa cells and related metabolic disorders. We noted that isoleucine recovered the promotive effect on cell apoptosis, inhibitory effect on cell proliferation, sex hormone secretion, and mitochondrial function induced by dehydroepiandrosterone. Our gas chromatography-mass spectrometry targeted analysis (GC-MS/MS) revealed that isoleucine was significantly decreased in PCOS patients.
Based on these results, we speculate that metabolome alterations are vital in ameliorating PCOS symptoms. This may be a novel therapeutic target for PCOS treatment. Our study provides preliminary evidence that these findings will enhance our ability to accurately diagnose and intervene in PCOS.
多囊卵巢综合征(PCOS)是一种复杂的内分泌疾病,常伴有代谢紊乱。研究表明,脂肪组织(尤其是腹部脂肪组织)功能障碍会加重 PCOS 患者的生殖和代谢问题。脂肪组织分泌的信号介质(如脂质和代谢物)与其他器官(包括卵巢)相互作用,以维持全身平衡。
本研究采用基于液相色谱-质谱联用(LC-MS/MS)的代谢组学方法,对 PCOS 患者和正常个体的脂肪样本进行了检测。采用多变量统计分析方法筛选 PCOS 生物标志物。
我们的通路分析显示,这些差异代谢物可能参与了炎症性疾病和线粒体β氧化。我们进一步建立了体外 PCOS 细胞模型,以研究高雄性激素对颗粒细胞和相关代谢紊乱的影响。我们发现异亮氨酸可以恢复脱氢表雄酮诱导的细胞凋亡促进作用、细胞增殖抑制作用、性激素分泌和线粒体功能障碍。我们的气相色谱-质谱联用(GC-MS/MS)靶向分析显示,PCOS 患者的异亮氨酸显著减少。
基于这些结果,我们推测代谢组学改变对改善 PCOS 症状至关重要。这可能是 PCOS 治疗的新靶点。我们的研究初步证明,这些发现将提高我们准确诊断和干预 PCOS 的能力。