Application of the amniotic fluid metabolome to the study of fetal malformations, using Down syndrome as a specific model.
Mol Med Rep
; 16(5): 7405-7415, 2017 Nov.
Article
em En
| MEDLINE
| ID: mdl-28944830
ABSTRACT
Although monitoring and diagnosis of fetal diseases in utero remains a challenge, metabolomics may provide an additional tool to study the etiology and pathophysiology of fetal diseases at a functional level. In order to explore specific markers of fetal disease, metabolites were analyzed in two separate sets of experiments using amniotic fluid from fetuses with Down syndrome (DS) as a model. Both sets included 1015 pairs of controls and cases, and amniotic fluid samples were processed separately; metabolomic fingerprinting was then conducted using UPLCMS. Significantly altered metabolites involved in respective metabolic pathways were compared in the two experimental sets. In addition, significantly altered metabolic pathways were further compared with the genomic characters of the DS fetuses. The data suggested that metabolic profiles varied across different experiments, however alterations in the 4 metabolic pathways of the porphyrin metabolism, bile acid metabolism, hormone metabolism and amino acid metabolism, were validated for the two experimental sets. Significant changes in metabolites of coproporphyrin III, glycocholic acid, taurochenodeoxycholate, taurocholate, hydrocortisone, pregnenolone sulfate, Lhistidine, Larginine, Lglutamate and Lglutamine were further confirmed. Analysis of these metabolic alterations was linked to aberrant gene expression at chromosome 21 of the DS fetus. The decrease in coproporphyrin III in the DS fetus may portend abnormal erythropoiesis, and unbalanced glutamineglutamate concentration was observed to be closely associated with abnormal brain development in the DS fetus. Therefore, alterations in amniotic fluid metabolites may provide important clues to understanding the etiology of fetal disease and help to develop diagnostic testing for clinical applications.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Síndrome de Down
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Metaboloma
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Líquido Amniótico
Limite:
Adult
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Female
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Humans
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Male
Idioma:
En
Revista:
Mol Med Rep
Ano de publicação:
2017
Tipo de documento:
Article