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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MDPI AG
2023-01-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/1/139 |
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| author | Ignacio Valenzuela Katerina Zapletalova Marnel Greyling Yannick Regin Andre Gie David Basurto Jan Deprest Johannes van der Merwe |
| author_facet | Ignacio Valenzuela Katerina Zapletalova Marnel Greyling Yannick Regin Andre Gie David Basurto Jan Deprest Johannes van der Merwe |
| author_sort | Ignacio Valenzuela |
| collection | DOAJ |
| 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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| publishDate | 2023-01-01 |
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| spelling | doaj.art-2eff6563bf9148c2835aed5b6ba1f5c42023-11-30T21:19:59ZengMDPI AGBiomedicines2227-90592023-01-0111113910.3390/biomedicines11010139Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit ModelIgnacio Valenzuela0Katerina Zapletalova1Marnel Greyling2Yannick Regin3Andre Gie4David Basurto5Jan Deprest6Johannes van der Merwe7Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, BelgiumCluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, BelgiumCluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, BelgiumCluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, BelgiumDepartment of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town 7505, South AfricaCluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, BelgiumCluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, BelgiumCluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, BelgiumWe 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.https://www.mdpi.com/2227-9059/11/1/139fetal growth restrictionprematurityplacental insufficiencyneurodevelopmentlung developmentanimal model |
| spellingShingle | Ignacio Valenzuela Katerina Zapletalova Marnel Greyling Yannick Regin Andre Gie David Basurto Jan Deprest Johannes van der Merwe Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model Biomedicines fetal growth restriction prematurity placental insufficiency neurodevelopment lung development animal 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 | fetal growth restriction prematurity placental insufficiency neurodevelopment lung development animal model |
| url | https://www.mdpi.com/2227-9059/11/1/139 |
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