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Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis

BACKGROUND: Intrauterine growth restriction (IUGR) is among the most challenging problems in antenatal care. Several factors implicated in the pathophysiology of IUGR have been identified. We aimed to investigate the effect of UPI on lung development by identifying metabolic changes during the first...

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Autores principales: Yuliana, Merryl Esther, Huang, Zheng-Hao, Chou, Hsiu-Chu, Chen, Chung-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492919/
https://www.ncbi.nlm.nih.gov/pubmed/36160795
http://dx.doi.org/10.3389/fped.2022.952313
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author Yuliana, Merryl Esther
Huang, Zheng-Hao
Chou, Hsiu-Chu
Chen, Chung-Ming
author_facet Yuliana, Merryl Esther
Huang, Zheng-Hao
Chou, Hsiu-Chu
Chen, Chung-Ming
author_sort Yuliana, Merryl Esther
collection PubMed
description BACKGROUND: Intrauterine growth restriction (IUGR) is among the most challenging problems in antenatal care. Several factors implicated in the pathophysiology of IUGR have been identified. We aimed to investigate the effect of UPI on lung development by identifying metabolic changes during the first seven days of postnatal life. MATERIALS AND METHODS: On gestation day 17, four time-dated pregnant Sprague Dawley rats were randomized to a IUGR group or a control group, which underwent an IUGR protocol comprising bilateral uterine vessel ligation and sham surgery, respectively. On gestation day 22, 39 control and 26 IUGR pups were naturally delivered. The rat pups were randomly selected from the control and IUGR group on postnatal day 7. The pups' lungs were excised for histological, Western blot, and metabolomic analyses. Liquid chromatography mass spectrometry was performed for metabolomic analyses. RESULTS: UPI induced IUGR, as evidenced by the IUGR rat pups having a significantly lower average body weight than the control rat pups on postnatal day 7. The control rats exhibited healthy endothelial cell healthy and vascular development, and the IUGR rats had a significantly lower average radial alveolar count than the control rats. The mean birth weight of the 26 IUGR rats (5.89 ± 0.74 g) was significantly lower than that of the 39 control rats (6.36 ± 0.55 g; p < 0.01). UPI decreased the levels of platelet-derived growth factor-A (PDGF-A) and PDGF-B in the IUGR newborn rats. One-way analysis of variance revealed 345 features in the pathway, 14 of which were significant. Regarding major differential metabolites, 10 of the 65 metabolites examined differed significantly between the groups (p < 0.05). Metabolite pathway enrichment analysis revealed significant between-group differences in the metabolism of glutathione, arginine–proline, thiamine, taurine–hypotaurine, pantothenate, alanine–aspartate–glutamate, cysteine–methionine, glycine–serine–threonine, glycerophospholipid, and purine as well as in the biosynthesis of aminoacyl-tRNA, pantothenate, and CoA. CONCLUSIONS: UPI alters lung development and metabolomics in growth-restricted newborn rats. Our findings may elucidate new metabolic mechanisms underlying IUGR-induced altered lung development and serve as a reference for the development of prevention and treatment strategies for IUGR-induced altered lung development.
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spelling pubmed-94929192022-09-23 Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis Yuliana, Merryl Esther Huang, Zheng-Hao Chou, Hsiu-Chu Chen, Chung-Ming Front Pediatr Pediatrics BACKGROUND: Intrauterine growth restriction (IUGR) is among the most challenging problems in antenatal care. Several factors implicated in the pathophysiology of IUGR have been identified. We aimed to investigate the effect of UPI on lung development by identifying metabolic changes during the first seven days of postnatal life. MATERIALS AND METHODS: On gestation day 17, four time-dated pregnant Sprague Dawley rats were randomized to a IUGR group or a control group, which underwent an IUGR protocol comprising bilateral uterine vessel ligation and sham surgery, respectively. On gestation day 22, 39 control and 26 IUGR pups were naturally delivered. The rat pups were randomly selected from the control and IUGR group on postnatal day 7. The pups' lungs were excised for histological, Western blot, and metabolomic analyses. Liquid chromatography mass spectrometry was performed for metabolomic analyses. RESULTS: UPI induced IUGR, as evidenced by the IUGR rat pups having a significantly lower average body weight than the control rat pups on postnatal day 7. The control rats exhibited healthy endothelial cell healthy and vascular development, and the IUGR rats had a significantly lower average radial alveolar count than the control rats. The mean birth weight of the 26 IUGR rats (5.89 ± 0.74 g) was significantly lower than that of the 39 control rats (6.36 ± 0.55 g; p < 0.01). UPI decreased the levels of platelet-derived growth factor-A (PDGF-A) and PDGF-B in the IUGR newborn rats. One-way analysis of variance revealed 345 features in the pathway, 14 of which were significant. Regarding major differential metabolites, 10 of the 65 metabolites examined differed significantly between the groups (p < 0.05). Metabolite pathway enrichment analysis revealed significant between-group differences in the metabolism of glutathione, arginine–proline, thiamine, taurine–hypotaurine, pantothenate, alanine–aspartate–glutamate, cysteine–methionine, glycine–serine–threonine, glycerophospholipid, and purine as well as in the biosynthesis of aminoacyl-tRNA, pantothenate, and CoA. CONCLUSIONS: UPI alters lung development and metabolomics in growth-restricted newborn rats. Our findings may elucidate new metabolic mechanisms underlying IUGR-induced altered lung development and serve as a reference for the development of prevention and treatment strategies for IUGR-induced altered lung development. Frontiers Media S.A. 2022-09-08 /pmc/articles/PMC9492919/ /pubmed/36160795 http://dx.doi.org/10.3389/fped.2022.952313 Text en Copyright © 2022 Yuliana, Huang, Chou and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pediatrics
Yuliana, Merryl Esther
Huang, Zheng-Hao
Chou, Hsiu-Chu
Chen, Chung-Ming
Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis
title Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis
title_full Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis
title_fullStr Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis
title_full_unstemmed Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis
title_short Effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: A metabolomic analysis
title_sort effects of uteroplacental insufficiency on growth-restricted rats with altered lung development: a metabolomic analysis
topic Pediatrics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9492919/
https://www.ncbi.nlm.nih.gov/pubmed/36160795
http://dx.doi.org/10.3389/fped.2022.952313
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