abstract
We report on the first untargeted UPLC-MS study of 2nd trimester maternal urine and amniotic fluid (AF), to investigate the possible metabolic effects of fetal malformations (FM), gestational diabetes mellitus (GDM) and preterm delivery (PTD). For fetal malformations, considerable metabolite variations were identified in AF and, to a lesser extent, in urine. Using validated PLS-DA models and statistical correlations between UPLC-MS data and previously acquired NMR data, a metabolic picture of fetal hypoxia, enhanced gluconeogenesis, TCA activity and hindered kidney development affecting FM pregnancies was reinforced. Moreover, changes in carnitine, pyroglutamate and polyols were newly noted, respectively, reflecting lipid oxidation, altered placental amino acid transfer and alterations in polyol pathways. Higher excretion of conjugated products in maternal urine was seen suggesting alterations in conjugation reactions. For the pre-diagnostic GDM group, no significant changes were observed, either considering amniotic fluid or maternal urine, whereas, for the pre-PTD group, some newly observed changes were noted, namely, the decrease of particular amino acids and the increase of an hexose (possibly glucose), suggesting alteration in placental amino acid fluxes and a possible tendency for hyperglycemia. This work shows the potential of UPLC-MS for the study of fetal and maternal biofluids, particularly when used in tandem with comparable NMR data. The important roles played by sampling characteristics (e.g. group dimensions) and the specific experimental conditions chosen for MS methods are discussed.
keywords
NUCLEAR-MAGNETIC-RESONANCE; MASS-SPECTROMETRY; STATISTICAL HETEROSPECTROSCOPY; PRENATAL DISORDERS; PRETERM INFANTS; PEAK ALIGNMENT; DATA SETS; PREECLAMPSIA; METABONOMICS; H-1-NMR
subject category
Biochemistry & Molecular Biology
authors
Graca, G; Goodfellow, BJ; Barros, AS; Diaz, S; Duarte, IF; Spagou, K; Veselkov, K; Want, EJ; Lindon, JC; Carreira, IM; Galhano, E; Pita, C; Gil, AM
our authors
Ana Maria Pissarra Coelho Gil
Associate Professor with Aggregation
Ana Maria Rebelo Barreto Xavier
Assistant Professor
António de Sousa Barros
Post-doc Fellowship
Brian James Goodfellow
Assistant Professor
Iola Melissa Fernandes Duarte
Principal Researcheracknowledgements
Funding is acknowledged from the European Regional Development Fund through the Competitive Factors Thematic Operational Programme and from the Foundation for Science and Technology (FCT), Portugal (research project PTDC/QUI/66523/2006 and research grants SFRH/BD/41869/2007 and SFRH/BD/64159/2009). EW acknowledges Waters Corporation for funding. The Portuguese National NMR Network (RNRMN), supported with FCT funds is also acknowledged and the authors are grateful to M. Spraul, Bruker BioSpin, Germany, for providing access to spectral NMR databases.