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非靶向代谢组学分析揭示了复发性自然流产中代谢紊乱和氧化应激的加剧。

Untargeted metabolomics analysis reveals the metabolic disturbances and exacerbation of oxidative stress in recurrent spontaneous abortion.

机构信息

Obstetrics and Gynecology, The Affiliated Hospital of Inner Mongolia Medical University, Huhhot, China.

Obstetrics department, Chifeng Municipal Hospital, Chifeng, China.

出版信息

PLoS One. 2023 Dec 21;18(12):e0296122. doi: 10.1371/journal.pone.0296122. eCollection 2023.

Abstract

BACKGROUND

Recurrent spontaneous abortion (RSA) is characterized by the occurrence of two or more consecutive spontaneous abortions, with a rising prevalence among pregnant women and significant implications for their physical and mental well-being. The multifaceted etiology of RSA has posed challenges in unraveling the molecular mechanisms underlying that underlie its pathogenesis. Oxidative stress and immune response have been identified as pivotal factors in the development of its condition.

METHODS

Eleven serum samples from healthy pregnant women and 17 from RSA were subjected to liquid chromatography/mass spectrometry (LC-MS) analysis. Multivariate statistical analysis was employed to excavate system-level characterization of the serum metabolome. The measurement of seven oxidative stress products, namely superoxide dismutase (SOD), catalase (CAT), malonaldehyde (MDA), glutathione (GPx), glutathione peroxidase (GSH), oxidized glutathione (GSSG), heme oxygenase (HO-1), was carried out using ELISA.

RESULTS

Through the monitoring of metabolic and lipid alternations during RSA events, we have identified 816 biomarkers that were implicated in various metabolic pathways, including glutathione metabolism, phosphonate and phosphinate metabolism, nucleotide metabolism, sphingolipid metabolism, lysine degradation and purine metabolism, etc. These pathways have been found to be closely associated with the progression of the disease. Our finding indicated that the levels of MDA and HO-1 were elevated in the RSA group compared to the control group, whereas SOD, CAT and GPx exhibited a contrary pattern. However, no slight difference was observed in GSH and GSSG levels between the RSA group and the control group.

CONCLUSION

The manifestation of RSA elicited discernible temporal alternations in the serum metabolome and biochemical markers linked to the metabolic pathways of oxidative stress and immune response. Our investigation furnished a more comprehensive analytical framework encompassing metabolites and enzymes associated with oxidative stress. This inquiry furnished a more nuanced comprehension of the pathogenesis of RSA and established the ground work for prognostication and prophylaxis.

摘要

背景

复发性自然流产(RSA)的特征是连续发生两次或更多次自然流产,在孕妇中的发病率不断上升,对她们的身心健康有重大影响。RSA 的多因素病因使得阐明其发病机制的分子机制具有挑战性。氧化应激和免疫反应已被确定为该病发展的关键因素。

方法

对 11 例健康孕妇和 17 例 RSA 患者的血清样本进行液相色谱/质谱(LC-MS)分析。采用多变量统计分析方法挖掘血清代谢组的系统水平特征。采用 ELISA 法测定超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、丙二醛(MDA)、谷胱甘肽(GPx)、谷胱甘肽过氧化物酶(GSH)、氧化型谷胱甘肽(GSSG)、血红素加氧酶(HO-1)等 7 种氧化应激产物的水平。

结果

通过监测 RSA 事件期间的代谢和脂质变化,我们鉴定出了 816 种与各种代谢途径相关的生物标志物,包括谷胱甘肽代谢、膦酸和膦酸盐代谢、核苷酸代谢、鞘脂代谢、赖氨酸降解和嘌呤代谢等。这些途径与疾病的进展密切相关。我们的研究结果表明,与对照组相比,RSA 组的 MDA 和 HO-1 水平升高,而 SOD、CAT 和 GPx 则呈现相反的模式。然而,RSA 组和对照组之间 GSH 和 GSSG 水平没有明显差异。

结论

RSA 的表现引起了血清代谢组和与氧化应激和免疫反应代谢途径相关的生化标志物的明显时间变化。我们的研究提供了一个更全面的分析框架,包括与氧化应激相关的代谢物和酶。这项研究提供了对 RSA 发病机制的更细致理解,并为预测和预防奠定了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c96e/10735046/1fd0c36f81ec/pone.0296122.g001.jpg

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