abstract
This work describes an exploratory NMR metabonomic study of second trimester maternal urine and plasma, in an attempt to characterize the metabolic changes underlying prenatal disorders and identify possible early biomarkers. Fetal malformations have the strongest metabolic impact in both biofluids, suggesting effects due to hypoxia (leading to hypoxanthine increased excretion) and a need for enhanced gluconeogenesis, with higher ketone bodies (acetone and 3-hydroxy-butyric acid) production and TCA cycle demand (suggested by glucogenic amino acids and cis-aconitate overproduction). Choline and nucleotide metabolisms also seem affected and a distinct plasma lipids profile is observed for mothers with fetuses affected by central nervous system malformations. Urine from women who subsequently develop gestational diabetes mellitus exhibits higher 3-hydroxyisovalerate and 2-hydroxyisobutyrate levels, probably due to altered biotin status and amino acid and/or gut metabolisms (the latter possibly related to higher BMI values). Other urinary changes suggest choline and nucleotide metabolic alterations, whereas lower plasma betaine and TMAO levels are found. Chromosomal disorders and pre-preterm delivery groups show urinary changes in choline and, in the latter case, in 2-hydroxyisobutyrate. These results show that NMR metabonomics of maternal biofluids enables the noninvasive detection of metabolic changes associated to prenatal disorders, thus unveiling potential disorder biomarkers.
keywords
NUCLEAR-MAGNETIC-RESONANCE; GESTATIONAL DIABETES-MELLITUS; HUMAN AMNIOTIC-FLUID; OXIDATIVE STRESS; SPECTROSCOPY; PREGNANCY; FETAL; PREECLAMPSIA; DEFECTS; CHOLINE
subject category
Biochemistry & Molecular Biology
authors
Diaz, SO; Pinto, J; Graca, G; Duarte, IF; Barros, AS; Galhano, E; Pita, C; Almeida, MD; Goodfellow, BJ; Carreira, IM; Gil, AM
our authors
Ana Maria Pissarra Coelho Gil
Associate Professor with Aggregation
António de Sousa Barros
Post-doc Fellowship
Brian James Goodfellow
Assistant Professor
Iola Melissa Fernandes Duarte
Principal Researcher
Joana Isabel Monteiro Pinto
Post-doc Fellowshipacknowledgements
We acknowledge the Foundation for Science and Technology (FCT), Portugal, for funding through research project PTDC/QUI/66523/2006 and grants SFRH/BD/41869/2007, SFRH/BD/64159/2009 and SFRH/BD/73343/2010 for G.G., S.D., and J.P., respectively. The Portuguese National NMR Network (RNRMN), supported with FCT funds is also acknowledged and we are grateful to M. Spraul, Bruker BioSpin, Germany, for providing access to spectral databases.