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Sci Rep

Title:		Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model
Author(s):		Valenzuela I; Basurto D; Regin Y; Gie A; van der Veeken L; Vergote S; Munoz-Moreno E; Leszczynski B; Tielemans B; Velde GV; Deprest J; van der Merwe J;
Address:		"Department of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU Leuven, Herestraat 49, Box 805, 3000, Leuven, Belgium. Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town, South Africa. Magnetic Resonance Imaging Core Facility, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain. Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, Lojasiewicza 11, 30-348, Krakow, Poland. Biomedical MRI/MoSAIC, Faculty of Medicine, Department of Imaging and Pathology, KU Leuven Herestraat 49, 3000, Leuven, Belgium. Department of Development and Regeneration, Cluster Woman and Child, Group Biomedical Sciences, KU Leuven, Herestraat 49, Box 805, 3000, Leuven, Belgium. jan.deprest@uzleuven.be. Department of Obstetrics and Gynecology, Division Woman and Child, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. jan.deprest@uzleuven.be. Department of Obstetrics and Gynecology, Division Woman and Child, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium"
Journal Title:		Sci Rep
Year:		2022
Volume:		20221116
Issue:		1
Page Number:		19720 -
DOI:		10.1038/s41598-022-22895-6
ISSN/ISBN:		2045-2322 (Electronic) 2045-2322 (Linking)
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"
Keywords:		"Animals Rabbits Female Pregnancy Humans *Fetal Growth Retardation *Placenta/pathology Brain/pathology Models, Animal Lung/pathology;"
Notes:		"MedlineValenzuela, Ignacio Basurto, David Regin, Yannick Gie, Andre van der Veeken, Lennart Vergote, Simen Munoz-Moreno, Emma Leszczynski, Bartosz Tielemans, Birger Velde, Greetje Vande Deprest, Jan van der Merwe, Johannes eng 765274/Horizon 2020 Framework Programme/ Research Support, Non-U.S. Gov't England 2022/11/18 Sci Rep. 2022 Nov 16; 12(1):19720. doi: 10.1038/s41598-022-22895-6"