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http://hdl.handle.net/2445/121873
Title: | Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain |
Author: | Vliet, Erwin van Eixarch Roca, Elisenda Illa Armengol, Míriam Arbat-Plana, Ariadna González Tendero, Anna Hogberg, Helena T. Zhao, Liang Hartung, Thomas Gratacós Solsona, Eduard |
Keywords: | Neonatologia Metabolisme Cervell Neonatology Metabolism Brain |
Issue Date: | 27-May-2013 |
Publisher: | Public Library of Science (PLoS) |
Abstract: | Background: Intrauterine Growth Restriction (IUGR) due to placental insufficiency occurs in 5-10% of pregnancies and is a major risk factor for abnormal neurodevelopment. The perinatal diagnosis of IUGR related abnormal neurodevelopment represents a major challenge in fetal medicine. The development of clinical biomarkers is considered a promising approach, but requires the identification of biochemical/molecular alterations by IUGR in the fetal brain. This targeted metabolomics study in a rabbit IUGR model aimed to obtain mechanistic insight into the effects of IUGR on the fetal brain and identify metabolite candidates for biomarker development. Methodology/Principal Findings: At gestation day 25, IUGR was induced in two New Zealand rabbits by 40-50% uteroplacental vessel ligation in one horn and the contralateral horn was used as control. At day 30, fetuses were delivered by Cesarian section, weighed and brains collected for metabolomics analysis. Results showed that IUGR fetuses had a significantly lower birth and brain weight compared to controls. Metabolomics analysis using liquid chromatographyquadrupole time-of-flight mass spectrometry (LC-QTOF-MS) and database matching identified 78 metabolites. Comparison of metabolite intensities using a t-test demonstrated that 18 metabolites were significantly different between control and IUGR brain tissue, including neurotransmitters/peptides, amino acids, fatty acids, energy metabolism intermediates and oxidative stress metabolites. Principle component and hierarchical cluster analysis showed cluster formations that clearly separated control from IUGR brain tissue samples, revealing the potential to develop predictive biomarkers. Moreover birth weight and metabolite intensity correlations indicated that the extent of alterations was dependent on the severity of IUGR. Conclusions: IUGR leads to metabolic alterations in the fetal rabbit brain, involving neuronal viability, energy metabolism, amino acid levels, fatty acid profiles and oxidative stress mechanisms. Overall findings identified aspargine, ornithine, Nacetylaspartylglutamic acid, N-acetylaspartate and palmitoleic acid as potential metabolite candidates to develop clinical biomarkers for the perinatal diagnosis of IUGR related abnormal neurodevelopment. |
Note: | Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0064545 |
It is part of: | PLoS One, 2013, vol. 8, num. 5, p. e64545 |
URI: | http://hdl.handle.net/2445/121873 |
Related resource: | https://doi.org/10.1371/journal.pone.0064545 |
ISSN: | 1932-6203 |
Appears in Collections: | Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer) Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques) Articles publicats en revistes (BCNatal Fetal Medicine Research Center) |
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