Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model
Abstract Fetal growth restriction is one of the leading causes of perinatal mortality and morbidity and has consequences that extend well beyond the neonatal period. Current management relies on timely delivery rather than improving placental function. Several prenatal strategies have failed to show...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-11-01
|
| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-22895-6 |
| _version_ | 1811319608434491392 |
|---|---|
| author | Ignacio Valenzuela David Basurto Yannick Regin Andre Gie Lennart van der Veeken Simen Vergote Emma Muñoz-Moreno Bartosz Leszczynski Birger Tielemans Greetje Vande Velde Jan Deprest Johannes van der Merwe |
| author_facet | Ignacio Valenzuela David Basurto Yannick Regin Andre Gie Lennart van der Veeken Simen Vergote Emma Muñoz-Moreno Bartosz Leszczynski Birger Tielemans Greetje Vande Velde Jan Deprest Johannes van der Merwe |
| author_sort | Ignacio Valenzuela |
| collection | DOAJ |
| description | Abstract Fetal growth restriction is one of the leading causes of perinatal mortality and morbidity and has consequences that extend well beyond the neonatal period. Current management relies on timely delivery rather than improving placental function. Several prenatal strategies have failed to show benefit in clinical trials after promising results in animal models. Most of these animal models have important developmental and structural differences compared to the human and/or are insufficiently characterized. We aimed to describe placental function and structure in an FGR rabbit model, and to characterize the early brain and lung developmental morbidity using a multimodal approach. FGR was induced in time-mated rabbits at gestational day 25 by partial uteroplacental vessel ligation in one horn. Umbilical artery Doppler was measured before caesarean delivery at gestational day 30, and placentas were harvested for computed microtomography and histology. Neonates underwent neurobehavioral or pulmonary functional assessment the day after delivery, followed by brain or lung harvesting, respectively. Neuropathological assessment included multiregional quantification of neuron density, apoptosis, astrogliosis, cellular proliferation, and oligodendrocyte progenitors. Brain region volumes and diffusion metrics were obtained from ex-vivo brain magnetic resonance imaging. Lung assessment included biomechanical tests and pulmonary histology. Fetal growth restriction was associated with labyrinth alterations in the placenta, driven by fetal capillary reduction, and overall reduced vessels volume. FGR caused altered neurobehavior paralleled by regional neuropathological deficits and reduced fractional anisotropy in the cortex, white matter, and hippocampus. In addition, FGR kittens presented functional alterations in the peripheral lung and structurally underdeveloped alveoli. In conclusion, in a uteroplacental insufficiency FGR rabbit model, placental vascular alterations coincide with neurodevelopmental and pulmonary disruption. |
| first_indexed | 2024-04-13T12:45:57Z |
| format | Article |
| id | doaj.art-bf367b1fdc4146d4a7da0780406be9fe |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T12:45:57Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-bf367b1fdc4146d4a7da0780406be9fe2022-12-22T02:46:22ZengNature PortfolioScientific Reports2045-23222022-11-0112111210.1038/s41598-022-22895-6Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction modelIgnacio Valenzuela0David Basurto1Yannick Regin2Andre Gie3Lennart van der Veeken4Simen Vergote5Emma Muñoz-Moreno6Bartosz Leszczynski7Birger Tielemans8Greetje Vande Velde9Jan Deprest10Johannes van der Merwe11Department of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenDepartment of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenDepartment of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenDepartment of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenDepartment of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenDepartment of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenMagnetic Resonance Imaging Core Facility, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian UniversityBiomedical MRI/MoSAIC, Faculty of Medicine, Department of Imaging and PathologyBiomedical MRI/MoSAIC, Faculty of Medicine, Department of Imaging and PathologyDepartment of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenDepartment of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU LeuvenAbstract Fetal growth restriction is one of the leading causes of perinatal mortality and morbidity and has consequences that extend well beyond the neonatal period. Current management relies on timely delivery rather than improving placental function. Several prenatal strategies have failed to show benefit in clinical trials after promising results in animal models. Most of these animal models have important developmental and structural differences compared to the human and/or are insufficiently characterized. We aimed to describe placental function and structure in an FGR rabbit model, and to characterize the early brain and lung developmental morbidity using a multimodal approach. FGR was induced in time-mated rabbits at gestational day 25 by partial uteroplacental vessel ligation in one horn. Umbilical artery Doppler was measured before caesarean delivery at gestational day 30, and placentas were harvested for computed microtomography and histology. Neonates underwent neurobehavioral or pulmonary functional assessment the day after delivery, followed by brain or lung harvesting, respectively. Neuropathological assessment included multiregional quantification of neuron density, apoptosis, astrogliosis, cellular proliferation, and oligodendrocyte progenitors. Brain region volumes and diffusion metrics were obtained from ex-vivo brain magnetic resonance imaging. Lung assessment included biomechanical tests and pulmonary histology. Fetal growth restriction was associated with labyrinth alterations in the placenta, driven by fetal capillary reduction, and overall reduced vessels volume. FGR caused altered neurobehavior paralleled by regional neuropathological deficits and reduced fractional anisotropy in the cortex, white matter, and hippocampus. In addition, FGR kittens presented functional alterations in the peripheral lung and structurally underdeveloped alveoli. In conclusion, in a uteroplacental insufficiency FGR rabbit model, placental vascular alterations coincide with neurodevelopmental and pulmonary disruption.https://doi.org/10.1038/s41598-022-22895-6 |
| spellingShingle | Ignacio Valenzuela David Basurto Yannick Regin Andre Gie Lennart van der Veeken Simen Vergote Emma Muñoz-Moreno Bartosz Leszczynski Birger Tielemans Greetje Vande Velde Jan Deprest Johannes van der Merwe Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model Scientific Reports |
| title | Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model |
| title_full | Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model |
| title_fullStr | Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model |
| title_full_unstemmed | Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model |
| title_short | Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model |
| title_sort | placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model |
| url | https://doi.org/10.1038/s41598-022-22895-6 |
| work_keys_str_mv | AT ignaciovalenzuela placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT davidbasurto placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT yannickregin placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT andregie placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT lennartvanderveeken placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT simenvergote placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT emmamunozmoreno placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT bartoszleszczynski placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT birgertielemans placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT greetjevandevelde placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT jandeprest placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel AT johannesvandermerwe placentalvascularalterationsareassociatedwithearlyneurodevelopmentalandpulmonaryimpairmentintherabbitfetalgrowthrestrictionmodel |