abstract
In this work, untargeted NMR metabonomics was employed to evaluate the effects of pregnancy on the metabolite composition of maternal urine, thus establishing a control excretory trajectory for healthy pregnancies. Urine was collected for independent groups of healthy nonpregnant and pregnant women (in first, second, third trimesters) and multivariate analysis performed on the corresponding NMR spectra. Models were validated through Monte Carlo Cross Validation and permutation tests and metabolite correlations measured through Statistical Total Correlation Spectroscopy. The levels of 21 metabolites were found to change significantly throughout pregnancy, with variations observed for the first time to our knowledge for choline, creatinine, 4-deoxyerythronic acid, 4-deoxythreonic acid, furoylglycine, guanidoacetate, 3-hydroxybutyrate, and lactate. Results confirmed increased aminoaciduria across pregnancy and suggested (a) a particular involvement of isoleucine and threonine in lipid oxidation/ketone body synthesis, (b) a relation of excreted choline, taurine, and guanidoacetate to methionine metabolism and urea cycle regulation, and (c) a possible relationship of furoylglycine and creatinine to pregnancy, based on a tandem study of nonfasting confounding effects. Results demonstrate the usefulness of untargeted metabonomics in finding biomarker metabolic signatures for healthy pregnancies, against which disease-related deviations may be confronted in future studies, as a base for improved diagnostics and prediction.
keywords
TRIMESTER AMNIOTIC-FLUID; GESTATIONAL-AGE; PRENATAL DISORDERS; DISEASE DIAGNOSIS; MATERNAL URINE; ORGANIC-ACIDS; BIOMARKERS; 2ND; PREECLAMPSIA; SPECTROSCOPY
subject category
Biochemistry & Molecular Biology
authors
Diaz, SO; Barros, AS; Goodfellow, BJ; Duarte, IF; Carreira, IM; Galhano, E; Pita, C; Almeida, MD; 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 ResearcherProjects
acknowledgements
Funding is acknowledged from the European Regional Development Fund (FEDER) through the Competitive Factors Thematic Operational Programme (COMPETE) and from the Foundation for Science and Technology (FCT), Portugal, under the projects Pest-C/CTM/LA0011/2011, PTDC/QUI/66523/2006, and grant SFRH/BD/64159/2009. The authors are grateful to the Portuguese National NMR Network (RNRMN), supported with FCT funds, and to M. Spraul, Bruker BioSpin, Germany, for providing access to spectral databases.