Altered plasma levels of arachidonic acid, choline, amino acids, and sphingolipids signal neural tube defects

Şule Özel; Ozan Kaplan; Bilge Başak Fidan; Mustafa Çelebier; Yaprak Engin-Üstün; Şule Özel; Ozan Kaplan; Bilge Başak Fidan; Mustafa Çelebier; Yaprak Engin-Üstün

doi:10.3934/molsci.2025006

AIMS Molecular Science

2025, Volume 12, Issue 1: 99-112. doi: 10.3934/molsci.2025006

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Research article

Altered plasma levels of arachidonic acid, choline, amino acids, and sphingolipids signal neural tube defects

Running title:Altered plasma metabolite profiles associated with neural tube defects

1.
Department of Obstetrics and Gynecology, University of Health Sciences, Bilkent City Hospital, Ankara, Turkiye
2.
Department of Analytical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkiye
3.
Department of Obstetrics and Gynecology, University of Health Sciences, Etlik Zubeyde Women's Health Training and Research Hospital, Ankara, Turkiye

Received: 23 October 2024 Revised: 17 March 2025 Accepted: 29 March 2025 Published: 31 March 2025

Neural tube defects (NTDs) are common congenital anomalies formed by the incomplete closure of the neural tube during early embryonic development. This study aims to identify potential plasma biomarkers associated with NTDs using an untargeted metabolomics approach, thereby enhancing the understanding of the disease pathogenesis and facilitating early diagnosis. Peripheral venous blood samples were obtained from 21 healthy controls and 20 individuals diagnosed with NTDs. Untargeted metabolomic profiling was performed using Quadrupole Time-of-Flight Liquid Chromatography Mass Spectrometry (Q-TOF LC/MS) in positive ion mode. Data processing was conducted using the XCMS package in R, thus identifying significant metabolites based on a fold change greater than 1.5 and a p-value less than 0.05. The analysis revealed significant alterations in several metabolites in NTD cases compared to the healthy controls. Notably, changes were observed in arachidonic acid and prostaglandins (lipid metabolism), choline (methylation processes), amino acids such as leucine, phenylalanine, and lysine (amino acid metabolism), thyrotropin-releasing hormone, vitamin D3, cob(II)alamin, and galactosylsphingosine (sphingolipid metabolism). The identified metabolites may play a role in the pathogenesis of NTDs and hold potential as early diagnostic biomarkers.
- neural tube defects,
- metabolomics,
- lipid metabolism,
- aminoacid metabolism,
- LC-MS/MS
Citation: Şule Özel, Ozan Kaplan, Bilge Başak Fidan, Mustafa Çelebier, Yaprak Engin-Üstün. Altered plasma levels of arachidonic acid, choline, amino acids, and sphingolipids signal neural tube defects[J]. AIMS Molecular Science, 2025, 12(1): 99-112. doi: 10.3934/molsci.2025006

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Abstract

Neural tube defects (NTDs) are common congenital anomalies formed by the incomplete closure of the neural tube during early embryonic development. This study aims to identify potential plasma biomarkers associated with NTDs using an untargeted metabolomics approach, thereby enhancing the understanding of the disease pathogenesis and facilitating early diagnosis. Peripheral venous blood samples were obtained from 21 healthy controls and 20 individuals diagnosed with NTDs. Untargeted metabolomic profiling was performed using Quadrupole Time-of-Flight Liquid Chromatography Mass Spectrometry (Q-TOF LC/MS) in positive ion mode. Data processing was conducted using the XCMS package in R, thus identifying significant metabolites based on a fold change greater than 1.5 and a p-value less than 0.05. The analysis revealed significant alterations in several metabolites in NTD cases compared to the healthy controls. Notably, changes were observed in arachidonic acid and prostaglandins (lipid metabolism), choline (methylation processes), amino acids such as leucine, phenylalanine, and lysine (amino acid metabolism), thyrotropin-releasing hormone, vitamin D3, cob(II)alamin, and galactosylsphingosine (sphingolipid metabolism). The identified metabolites may play a role in the pathogenesis of NTDs and hold potential as early diagnostic biomarkers.

Acknowledgments

We would like to thank Hacettepe University Faculty of Pharmacy—HÜNİKAL Laboratory for allowing us to access the Q-TOF LC/MS instrument.

Ethical approval

The ethics committee of Zekai Tahir Burak Women's Health Education and Research Hospital, Ministry of Health of the Republic of Turkiye approved this study (REC number: 73/2019). The authors state that they have obtained appropriate institutional review board approval and/or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. All participants included in the study were informed about the study design and signed an informed consent form before the onset of the study. Participants were informed they had the right to withdraw from the study at any stage.

Conflict of interest

The authors declare that they have no conflicts of interest or financial relationships that could have influenced the results or interpretation of this manuscript.

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