Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

<h4>Background</h4>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 medici...

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Autores principales:	Erwin van Vliet, Elisenda Eixarch, Miriam Illa, Ariadna Arbat-Plana, Anna González-Tendero, Helena T Hogberg, Liang Zhao, Thomas Hartung, Eduard Gratacos
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1914f6d86a8d4a6399ae2c3b88f4eac9
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spelling	oai:doaj.org-article:1914f6d86a8d4a6399ae2c3b88f4eac92021-11-18T07:44:14ZMetabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.1932-620310.1371/journal.pone.0064545https://doaj.org/article/1914f6d86a8d4a6399ae2c3b88f4eac92013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23724060/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 chromatography-quadrupole 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.<h4>Conclusions</h4>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, N-acetylaspartylglutamic acid, N-acetylaspartate and palmitoleic acid as potential metabolite candidates to develop clinical biomarkers for the perinatal diagnosis of IUGR related abnormal neurodevelopment.Erwin van VlietElisenda EixarchMiriam IllaAriadna Arbat-PlanaAnna González-TenderoHelena T HogbergLiang ZhaoThomas HartungEduard GratacosPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 5, p e64545 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Erwin van Vliet Elisenda Eixarch Miriam Illa Ariadna Arbat-Plana Anna González-Tendero Helena T Hogberg Liang Zhao Thomas Hartung Eduard Gratacos Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.
description	<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 chromatography-quadrupole 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.<h4>Conclusions</h4>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, N-acetylaspartylglutamic acid, N-acetylaspartate and palmitoleic acid as potential metabolite candidates to develop clinical biomarkers for the perinatal diagnosis of IUGR related abnormal neurodevelopment.
format	article
author	Erwin van Vliet Elisenda Eixarch Miriam Illa Ariadna Arbat-Plana Anna González-Tendero Helena T Hogberg Liang Zhao Thomas Hartung Eduard Gratacos
author_facet	Erwin van Vliet Elisenda Eixarch Miriam Illa Ariadna Arbat-Plana Anna González-Tendero Helena T Hogberg Liang Zhao Thomas Hartung Eduard Gratacos
author_sort	Erwin van Vliet
title	Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.
title_short	Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.
title_full	Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.
title_fullStr	Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.
title_full_unstemmed	Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.
title_sort	metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1914f6d86a8d4a6399ae2c3b88f4eac9
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Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain.

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