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非靶向代谢组学揭示流产中的关键途径:类固醇、叶酸、脂肪酸和糖胺聚糖代谢。

Untargeted metabolomics reveals key pathways in miscarriage: steroid, folate, fatty acid & glycosaminoglycan metabolism.

作者信息

Ku Chee Wai, Tan Yu Bin, Chew Kuan Yang, Ku Chee Onn, Ng Shi Tong Carissa, Tan Thiam Chye, Lee Yie Hou

机构信息

Department of Reproductive Medicine, KK Women's and Children's Hospital, Singapore, Singapore.

OBGYN-Academic Clinical Program, Duke-NUS Medical School, Singapore, Singapore.

出版信息

NPJ Womens Health. 2025;3(1):35. doi: 10.1038/s44294-025-00085-9. Epub 2025 Jun 13.

DOI:10.1038/s44294-025-00085-9
PMID:40519213
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12165837/
Abstract

Metabolites influencing miscarriage outcomes remain understudied. We hypothesized that aberrant metabolism impacts threatened miscarriage outcomes and that understanding these pathways could offer new management strategies. This case-control study analyzed serum metabolomics from 80 women between 5 and 12 weeks' gestation at KK Women's and Children's Hospital, Singapore, comparing three groups: women with threatened miscarriage who miscarried (TM), those with ongoing pregnancies (TM), and women with normal pregnancies (NP). Using untargeted liquid chromatography-mass spectrometry and pathway analysis through MetaboAnalyst 5.0 and the Kyoto Encyclopedia of Genes and Genomes, 267 metabolites across 12 enriched pathways were identified. Dysregulations in steroid (AUC 0.82), folate (AUC 0.59), fatty acid (AUC 0.70), and glucosaminoglycan (AUC 0.64) pathways distinguished women who miscarried from those with ongoing pregnancies (TM vs TM). We provide initial insights into the metabolic profile associated with miscarriage, highlighting disruptions in steroid hormone, fatty acid, folate, and glucosaminoglycan biosynthesis. Further validation may support biomarker development for prognostication.

摘要

影响流产结局的代谢物仍未得到充分研究。我们假设异常代谢会影响先兆流产结局,并且了解这些途径可能会提供新的管理策略。这项病例对照研究分析了新加坡KK妇女儿童医院80名妊娠5至12周妇女的血清代谢组学,比较了三组:流产的先兆流产妇女(TM)、持续妊娠的妇女(TM)和正常妊娠的妇女(NP)。使用非靶向液相色谱-质谱联用技术,并通过MetaboAnalyst 5.0和京都基因与基因组百科全书进行通路分析,在12条富集通路中鉴定出267种代谢物。类固醇(AUC 0.82)、叶酸(AUC 0.59)、脂肪酸(AUC 0.70)和糖胺聚糖(AUC 0.64)通路的失调区分了流产妇女和持续妊娠的妇女(TM与TM)。我们对与流产相关的代谢谱提供了初步见解,突出了类固醇激素、脂肪酸、叶酸和糖胺聚糖生物合成中的破坏。进一步的验证可能支持用于预后的生物标志物开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f564/12165837/2a2a67999d73/44294_2025_85_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f564/12165837/5aeb6e0c543e/44294_2025_85_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f564/12165837/9fd173ffbf48/44294_2025_85_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f564/12165837/2a2a67999d73/44294_2025_85_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f564/12165837/5aeb6e0c543e/44294_2025_85_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f564/12165837/9fd173ffbf48/44294_2025_85_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f564/12165837/2a2a67999d73/44294_2025_85_Fig3_HTML.jpg

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