Center for Reproductive Medicine, Zhongshan City People's Hospital, Zhongshan, China.
Department of Obstetrics and Gynecology, Center for Reproductive Medicine, The Third Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
Front Endocrinol (Lausanne). 2024 Oct 11;15:1426517. doi: 10.3389/fendo.2024.1426517. eCollection 2024.
Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder linked with endocrine and metabolic disturbances. The underlying mechanism of PCOS, especially its effect on oocyte competence, remains unclear. The study aimed to identify abnormal follicular metabolic changes using a multi-omics approach in follicular fluid from PCOS patients and to determine their effects on oocyte competence.
A total of 36 women with PCOS and 35 women without PCOS who underwent fertilization and embryo transfer were included in the study. Cumulus cells and follicular fluid samples were collected. Follicular fluid samples underwent metabolomic analysis, while cumulus cell clusters from the same patients were assessed using transcriptomic analysis. Clinical information of patients and assisted reproductive technology (ART) results were recorded. Transcriptomics and metabolomics were integrated to identify disrupted pathways, and receiver operation characteristics (ROC) analysis was conducted to identify potential diagnostic biomarkers for PCOS. Pearson correlation analysis was conducted to assess the relationship between metabolites in follicular fluid and oocyte competence (fertilization and early embryo development potential).
Through multi-omics analysis, we identified aberrantly expressed pathways at both transcriptional and metabolic levels, such as the citrate cycle (TCA cycle), oxidative phosphorylation, the cAMP signaling pathway, the mTOR signaling pathway, and steroid hormone biosynthesis. Ten candidate metabolites were identified based on metabolic profiling data from these altered pathways. Phytic acid, succinic acid, 2'-deoxyinosine triphosphate, and 4-trimethylammoniobutanoic acid in the follicular fluid exhibited high specificity and sensitivity in distinguishing PCOS. Among these metabolites, L-arginine showed a negative correlation with the 2PN fertilization rate and cleavage rate, while estrone sulfate showed a negative correlation with the high-quality embryo rate in the fertilization (IVF) cycle.
We have conducted a preliminary study of a novel metabolic signature in women with PCOS using a multi-omics approach. The alterations in key metabolic pathways may enhance our understanding of the pathogenesis of PCOS.
多囊卵巢综合征（PCOS）是一种常见的异质性疾病，与内分泌和代谢紊乱有关。PCOS 的潜在机制，尤其是其对卵母细胞能力的影响，尚不清楚。本研究旨在使用多组学方法在 PCOS 患者的卵泡液中识别异常的卵泡代谢变化，并确定其对卵母细胞能力的影响。
共纳入 36 名 PCOS 患者和 35 名未患 PCOS 的患者进行受精和胚胎移植。收集卵丘细胞和卵泡液样本。对卵泡液样本进行代谢组学分析，同时对来自同一患者的卵丘细胞簇进行转录组学分析。记录患者的临床信息和辅助生殖技术（ART）结果。整合转录组学和代谢组学以识别失调的途径，并进行接收者操作特征（ROC）分析以鉴定 PCOS 的潜在诊断生物标志物。进行 Pearson 相关性分析以评估卵泡液中代谢物与卵母细胞能力（受精和早期胚胎发育潜能）之间的关系。
通过多组学分析，我们在转录和代谢水平上均鉴定出异常表达的途径，如柠檬酸循环（TCA 循环）、氧化磷酸化、cAMP 信号通路、mTOR 信号通路和类固醇激素生物合成。根据这些改变途径的代谢谱数据分析，确定了 10 种候选代谢物。卵泡液中的植酸、琥珀酸、2'-脱氧肌苷三磷酸和 4-三甲氨基丁酸在区分 PCOS 方面具有较高的特异性和敏感性。在这些代谢物中，L-精氨酸与 2PN 受精率和卵裂率呈负相关，而雌酮硫酸盐与受精（IVF）周期中的优质胚胎率呈负相关。
我们使用多组学方法对 PCOS 女性进行了一项新的代谢特征的初步研究。关键代谢途径的改变可能有助于我们理解 PCOS 的发病机制。
