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

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...

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Autores: 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
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2013
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/121873
Acceso en línea:https://hdl.handle.net/2445/121873
Access Level:acceso abierto
Palabra clave:Neonatologia
Metabolisme
Cervell
Neonatology
Metabolism
Brain
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spelling Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brainVliet, Erwin vanEixarch Roca, ElisendaIlla Armengol, MíriamArbat-Plana, AriadnaGonzález Tendero, AnnaHogberg, Helena T.Zhao, LiangHartung, ThomasGratacós Solsona, EduardNeonatologiaMetabolismeCervellNeonatologyMetabolismBrainBackground: 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.Public Library of Science (PLoS)2018201820132018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion10 p.application/pdfhttps://hdl.handle.net/2445/121873Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1371/journal.pone.0064545PLoS One, 2013, vol. 8, num. 5, p. e64545https://doi.org/10.1371/journal.pone.0064545cc-by (c) Vliet, Erwin van et al., 2013http://creativecommons.org/licenses/by/3.0/esinfo:eu-repo/semantics/openAccessoai:recercat.cat:2445/1218732026-05-29T05:05:01Z
dc.title.none.fl_str_mv Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain
title Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain
spellingShingle Metabolomics reveals metabolic alterations by intrauterine growth restriction in the fetal rabbit brain
Vliet, Erwin van
Neonatologia
Metabolisme
Cervell
Neonatology
Metabolism
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
dc.creator.none.fl_str_mv 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
author Vliet, Erwin van
author_facet 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
author_role author
author2 Eixarch Roca, Elisenda
Illa Armengol, Míriam
Arbat-Plana, Ariadna
González Tendero, Anna
Hogberg, Helena T.
Zhao, Liang
Hartung, Thomas
Gratacós Solsona, Eduard
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Neonatologia
Metabolisme
Cervell
Neonatology
Metabolism
Brain
topic Neonatologia
Metabolisme
Cervell
Neonatology
Metabolism
Brain
description 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.
publishDate 2013
dc.date.none.fl_str_mv 2013
2018
2018
2018
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/121873
url https://hdl.handle.net/2445/121873
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0064545
PLoS One, 2013, vol. 8, num. 5, p. e64545
https://doi.org/10.1371/journal.pone.0064545
dc.rights.none.fl_str_mv cc-by (c) Vliet, Erwin van et al., 2013
http://creativecommons.org/licenses/by/3.0/es
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc-by (c) Vliet, Erwin van et al., 2013
http://creativecommons.org/licenses/by/3.0/es
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 10 p.
application/pdf
dc.publisher.none.fl_str_mv Public Library of Science (PLoS)
publisher.none.fl_str_mv Public Library of Science (PLoS)
dc.source.none.fl_str_mv Articles publicats en revistes (Cirurgia i Especialitats Medicoquirúrgiques)
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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