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卵巢反应不良的不孕个体卵泡液的非靶向代谢组学分析

Non-targeted metabolomic analysis of follicular fluid in infertile individuals with poor ovarian response.

作者信息

Guo Liang, Song Jiaming, Xia Xiyang, Jiang Jianya, Yang Yingying, Chen Wei, Chen Li, Xue Pingping

机构信息

Department of Reproductive Medicine Center, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.

Changzhou Key Laboratory of Maternal and Child Health Medicine, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.

出版信息

Front Endocrinol (Lausanne). 2025 May 12;16:1547550. doi: 10.3389/fendo.2025.1547550. eCollection 2025.

Abstract

BACKGROUND

Poor ovarian response (POR) is a pathological condition characterized by inadequate ovarian response to gonadotropin stimulation in patients undergoing fertilization and embryo transfer. It represents a primary cause of failure in many assisted reproductive technology treatments. Utilizing non-targeted metabolomics technology applied to follicular fluid, this research aims to elucidate the metabolic characteristics associated with POR, explore the underlying molecular mechanisms, and identify potential biomarkers. By analyzing metabolic factors that influence oocyte quality, we aspire to provide insights for the early detection and intervention of patients with POR.

METHODS

In this research, 60 follicular fluid samples were collected for a non-targeted metabolomic study, including 30 samples from POR patients and 30 from women with normal ovarian reserve. The orthogonal partial least squares discriminant analysis model was employed to discern separation trends between the two groups. Pathway enrichment analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Additionally, random forest and logistic regression models were utilized to identify biomarkers indicative of POR within the follicular fluid.

RESULTS

Based on data from the Human Metabolome Database, our metabolomic analysis identified 40 differential metabolites associated with POR, including 18 up-regulated and 22 down-regulated metabolites. KEGG pathway analysis revealed that these metabolites predominantly participate in glycerophospholipid metabolism, choline metabolism in cancer, autophagy processes. Notably, perillyl aldehyde emerged as a potential biomarker for POR.

CONCLUSIONS

This study represents the first comprehensive examination of metabolic alterations in follicular fluid among patients with POR using non-targeted metabolomics technology. We have identified significant metabolic changes within the follicular fluid of individuals affected by POR which may offer valuable insights into therapeutic strategies for managing this condition as well as improving outcomes in assisted reproductive technologies.

摘要

背景

卵巢反应不良(POR)是一种病理状态,其特征是在接受受精和胚胎移植的患者中,卵巢对促性腺激素刺激的反应不足。它是许多辅助生殖技术治疗失败的主要原因。本研究利用非靶向代谢组学技术分析卵泡液,旨在阐明与POR相关的代谢特征,探索潜在的分子机制,并识别潜在的生物标志物。通过分析影响卵母细胞质量的代谢因素,我们希望为POR患者的早期检测和干预提供见解。

方法

在本研究中,收集了60份卵泡液样本进行非靶向代谢组学研究,其中包括30份POR患者的样本和30份卵巢储备正常女性的样本。采用正交偏最小二乘法判别分析模型来识别两组之间的分离趋势。使用京都基因与基因组百科全书(KEGG)数据库进行通路富集分析。此外,利用随机森林和逻辑回归模型来识别卵泡液中指示POR的生物标志物。

结果

基于人类代谢组数据库的数据,我们的代谢组学分析确定了40种与POR相关的差异代谢物,其中18种上调,22种下调。KEGG通路分析表明,这些代谢物主要参与甘油磷脂代谢、癌症中的胆碱代谢、自噬过程。值得注意的是,紫苏醛成为POR的潜在生物标志物。

结论

本研究首次使用非靶向代谢组学技术全面检测了POR患者卵泡液中的代谢变化。我们已经确定了受POR影响个体卵泡液中的显著代谢变化,这可能为管理这种疾病的治疗策略以及改善辅助生殖技术的结果提供有价值的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee11/12104088/cee70ea5a30c/fendo-16-1547550-g001.jpg

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