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Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model

We previously reported the multi-system sequelae of fetal growth restriction, induced by placental underperfusion, in near-term born rabbits, in the immediate neonatal period and up to pre-adolescence. Herein, we describe the pulmonary and neurodevelopmental consequences of FGR in rabbits born prete...

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Autores principales: Valenzuela, Ignacio, Zapletalova, Katerina, Greyling, Marnel, Regin, Yannick, Gie, Andre, Basurto, David, Deprest, Jan, van der Merwe, Johannes
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855731/
https://www.ncbi.nlm.nih.gov/pubmed/36672647
http://dx.doi.org/10.3390/biomedicines11010139
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author Valenzuela, Ignacio
Zapletalova, Katerina
Greyling, Marnel
Regin, Yannick
Gie, Andre
Basurto, David
Deprest, Jan
van der Merwe, Johannes
author_facet Valenzuela, Ignacio
Zapletalova, Katerina
Greyling, Marnel
Regin, Yannick
Gie, Andre
Basurto, David
Deprest, Jan
van der Merwe, Johannes
author_sort Valenzuela, Ignacio
collection PubMed
description We previously reported the multi-system sequelae of fetal growth restriction, induced by placental underperfusion, in near-term born rabbits, in the immediate neonatal period and up to pre-adolescence. Herein, we describe the pulmonary and neurodevelopmental consequences of FGR in rabbits born preterm. We hypothesize that FGR has an additional detrimental effect on prematurity in both pulmonary function and neurodevelopment. FGR was induced at gestational day (GD) 25 by placental underperfusion, accomplished by partial uteroplacental vessel ligation in one uterine horn. Rabbits were delivered by cesarean section at GD 29, and placentas were harvested for histology. Neonates underwent neurobehavioral or pulmonary functional assessment at postnatal day 1, followed by brain or lung harvesting, respectively. The neurodevelopmental assessment included neurobehavioral testing and multiregional quantification of cell density and apoptosis in the brain. Lung assessment included functional testing, alveolar morphometry, and airway histology. FGR was associated with higher perinatal mortality, lower birth and placental weight, and a similar brain-to-body weight ratio compared to controls. Placental underperfusion decreased labyrinth and junction zone volumes in FGR placentas. FGR impaired pulmonary function, depicted by higher parenchymal resistance, damping, and elastance. Alveolar morphometry and airway smooth muscle content were comparable between groups. Neurobehavioral tests showed motoric and sensorial impairment in FGR rabbits. In FGR brains, cell density was globally reduced, with higher apoptosis in selected areas. In conclusion, in preterm-born rabbits, placental underperfusion leads to higher mortality, FGR, and impaired lung and brain development in early assessment. This study complements previous findings of placental, pulmonary, and neurodevelopmental impairment in near-term born rabbits in this model.
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spelling pubmed-98557312023-01-21 Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model Valenzuela, Ignacio Zapletalova, Katerina Greyling, Marnel Regin, Yannick Gie, Andre Basurto, David Deprest, Jan van der Merwe, Johannes Biomedicines Article We previously reported the multi-system sequelae of fetal growth restriction, induced by placental underperfusion, in near-term born rabbits, in the immediate neonatal period and up to pre-adolescence. Herein, we describe the pulmonary and neurodevelopmental consequences of FGR in rabbits born preterm. We hypothesize that FGR has an additional detrimental effect on prematurity in both pulmonary function and neurodevelopment. FGR was induced at gestational day (GD) 25 by placental underperfusion, accomplished by partial uteroplacental vessel ligation in one uterine horn. Rabbits were delivered by cesarean section at GD 29, and placentas were harvested for histology. Neonates underwent neurobehavioral or pulmonary functional assessment at postnatal day 1, followed by brain or lung harvesting, respectively. The neurodevelopmental assessment included neurobehavioral testing and multiregional quantification of cell density and apoptosis in the brain. Lung assessment included functional testing, alveolar morphometry, and airway histology. FGR was associated with higher perinatal mortality, lower birth and placental weight, and a similar brain-to-body weight ratio compared to controls. Placental underperfusion decreased labyrinth and junction zone volumes in FGR placentas. FGR impaired pulmonary function, depicted by higher parenchymal resistance, damping, and elastance. Alveolar morphometry and airway smooth muscle content were comparable between groups. Neurobehavioral tests showed motoric and sensorial impairment in FGR rabbits. In FGR brains, cell density was globally reduced, with higher apoptosis in selected areas. In conclusion, in preterm-born rabbits, placental underperfusion leads to higher mortality, FGR, and impaired lung and brain development in early assessment. This study complements previous findings of placental, pulmonary, and neurodevelopmental impairment in near-term born rabbits in this model. MDPI 2023-01-05 /pmc/articles/PMC9855731/ /pubmed/36672647 http://dx.doi.org/10.3390/biomedicines11010139 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Valenzuela, Ignacio
Zapletalova, Katerina
Greyling, Marnel
Regin, Yannick
Gie, Andre
Basurto, David
Deprest, Jan
van der Merwe, Johannes
Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model
title Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model
title_full Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model
title_fullStr Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model
title_full_unstemmed Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model
title_short Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model
title_sort fetal growth restriction impairs lung function and neurodevelopment in an early preterm rabbit model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855731/
https://www.ncbi.nlm.nih.gov/pubmed/36672647
http://dx.doi.org/10.3390/biomedicines11010139
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