Center for Reproductive Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, China.
Front Endocrinol (Lausanne). 2022 Sep 13;13:960274. doi: 10.3389/fendo.2022.960274. eCollection 2022.
Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder associated with multiple metabolic conditions including obesity, insulin resistance, and dyslipidemia. PCOS is the most common cause of anovulatory infertility; however, the molecular diversity of the ovarian follicle microenvironment is not fully understood. This study aimed to investigate the follicular fluid (FF) lipidomic profiles in different phenotypes of PCOS and to explore novel lipid biomarkers.
A total of 25 women with PCOS and 12 women without PCOS who underwent fertilization and embryo transfer were recruited, and their FF samples were collected for the lipidomic study. Liquid chromatography-tandem mass spectrometry was used to compare the differential abundance of FF lipids between patients with different PCOS phenotypes and controls. Subsequently, correlations between specific lipid concentrations in FF and high-quality embryo rate (HQER) were analyzed to further evaluate the potential interferences of lipid levels with oocyte quality in PCOS. Candidate biomarkers were then compared receiver operating characteristic (ROC) curve analysis.
In total, 19 lipids were identified in ovarian FF. Of these, the concentrations of ceramide (Cer) and free fatty acids (FFA) in FF were significantly increased, whereas those of lysophosphatidylglycerol (LPG) were reduced in women with PCOS compared to controls, especially in obese and insulin-resistant groups. In addition, six subclasses of ceramide, FFA, and LPG were correlated with oocyte quality. Twenty-three lipid subclasses were identified as potential biomarkers of PCOS, and ROC analysis indicated the prognostic value of Cer,36:1;2, FFA C14:1, and LPG,18:0 on HQER in patients with PCOS.
Our study showed the unique lipidomic profiles in FF from women with PCOS. Moreover, it provided metabolic signatures as well as candidate biomarkers that help to better understand the pathogenesis of PCOS.
多囊卵巢综合征(PCOS)是一种与多种代谢疾病相关的异质性内分泌紊乱,包括肥胖、胰岛素抵抗和血脂异常。PCOS 是无排卵性不孕的最常见原因;然而,卵巢卵泡微环境的分子多样性尚未完全阐明。本研究旨在探讨不同表型 PCOS 患者卵泡液(FF)的脂质组学特征,并探索新的脂质生物标志物。
共招募了 25 名 PCOS 患者和 12 名无 PCOS 患者进行受精和胚胎移植,采集其 FF 样本进行脂质组学研究。采用液相色谱-串联质谱法比较不同 PCOS 表型患者与对照组之间 FF 中脂质的差异丰度。随后,分析 FF 中特定脂质浓度与高质量胚胎率(HQER)之间的相关性,以进一步评估脂质水平对 PCOS 中卵母细胞质量的潜在干扰。然后通过受试者工作特征(ROC)曲线分析比较候选生物标志物。
共鉴定出 19 种卵巢 FF 中的脂质。与对照组相比,PCOS 患者 FF 中的神经酰胺(Cer)和游离脂肪酸(FFA)浓度显著升高,而溶血磷脂酰甘油(LPG)浓度降低,尤其是肥胖和胰岛素抵抗组。此外,Cer36:1、FFA C14:1 和 LPG18:0 等 6 种神经酰胺、FFA 和 LPG 亚类与卵母细胞质量相关。鉴定出 23 种潜在的 PCOS 脂质生物标志物,ROC 分析表明,Cer36:1;FFA C14:1 和 LPG18:0 对 PCOS 患者 HQER 具有预测价值。
本研究显示了 PCOS 患者 FF 中独特的脂质组学特征。此外,还提供了代谢特征和候选生物标志物,有助于更好地理解 PCOS 的发病机制。