Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Aug 11;21(5):106.
doi: 10.1007/s11306-025-02298-0.

Metabolic profiling of amniotic fluid by differential 12C-/13C-isotope dansylation labeling LC-MS for application in trisomy 21 fetuses

Ya-Ju Hsieh  1 , Yao-Lung Chang  2 , Yi-Hsin Wu  3 , Cheng-Yu Hung  1 , Liang Li  4 , Jau-Song Yu  1   3 , Chih-Hsiang Chang  5 , Wei-Ju Tu  3 , Yi-Ting Chen  6   7   8   9
Affiliations

Metabolic profiling of amniotic fluid by differential 12C-/13C-isotope dansylation labeling LC-MS for application in trisomy 21 fetuses

Ya-Ju Hsieh et al. Metabolomics. .

Abstract

Introduction: Down syndrome, caused by the triplication of human chromosome 21 (trisomy 21 [T21]) or its distal segment, is the most prevalent chromosomal anomaly associated with intellectual disability in newborns.

Objectives: To investigate the relationship between T21 and hydrops by analyzing metabolomic alterations, identifying correlations, and exploring pathway regulation mechanisms. This study goes beyond biomarker discovery, aiming to elucidate the pathogenesis of T21 and to explore the underlying mechanism.

Methods: We developed a 12C2-/13C2-isotope dansylation labeling LC-MS workflow to profile amine/phenol-based metabolomic differences in amniotic fluid (AF) between T21 and euploid fetuses.

Results: This workflow enabled the classification of AF specimens, revealing 138 increased and 116 decreased out of 2351 detected metabolites in T21 AF specimens. Metabolite identities were confirmed via LC-MS/MS spectral analysis using authentic standards. Dysregulated metabolites in T21 AF included markers of oxidative regulation and glutathione metabolism as well as those linked to fetal development. Further subgroup analysis identified 31 T21-associated metabolites, including significantly elevated androsterone sulfate in T21 AF both with and without hydrops. Among 30 hydrops-associated metabolites, most were reduced in hydrops AF, while hyaluronic acid (HA) was notably elevated only in T21 hydrops cases. Correlation analyses highlighted negative associations between HA and metabolites like kynurenine and homovanillic acid, suggesting potential roles in immune modulation and neuronal development in the fetal microenvironment.

Conclusion: This study identifies T21-associated metabolites that may serve as early diagnostic markers or therapeutic targets, offering insights into the metabolic landscape of Down syndrome and a foundation for exploring fetal therapeutic strategies.

Keywords: Amniotic fluid; Biomarker; Dansylation; Down syndrome; Hydrops fetalis; Isotopic chemical labeling; Metabolomics; Trisomy 21.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Similar articles

See all similar articles

References

    1. Achaintre, D., Bulete, A., Cren-Olive, C., Li, L., Rinaldi, S., & Scalbert, A. (2016). Differential isotope labeling of 38 dietary polyphenols and their quantification in urine by liquid chromatography electrospray ionization tandem mass spectrometry. Analytical Chemistry, 88, 2637–44. https://doi.org/10.1021/acs.analchem.5b03609 - DOI - PubMed
    1. Achaintre, D., Gicquiau, A., Li, L., Rinaldi, S., & Scalbert, A. (2018). Quantification of 38 dietary polyphenols in plasma by differential isotope labelling and liquid chromatography electrospray ionization tandem mass spectrometry. Journal of Chromatograpy A, 1558, 50–58. https://doi.org/10.1016/j.chroma.2018.05.017 - DOI
    1. Amorini, A. M., et al. (2012). Metabolic profile of amniotic fluid as a biochemical tool to screen for inborn errors of metabolism and fetal anomalies. Molecular Cell Biochemistry, 359, 205–16. https://doi.org/10.1007/s11010-011-1015-y - DOI
    1. Antonaros, F., et al. (2020). Plasma metabolome and cognitive skills in Down syndrome. Scientific Reports, 10, 10491. https://doi.org/10.1038/s41598-020-67195-z - DOI - PubMed - PMC
    1. Benacerraf, B. R. (2005). The role of the second trimester genetic sonogram in screening for fetal Down syndrome. Seminars Perinatology, 29, 386–94. https://doi.org/10.1053/j.semperi.2005.12.003 - DOI

LinkOut - more resources