PMID- 36672647 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230123 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 11 IP - 1 DP - 2023 Jan 5 TI - Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model. LID - 10.3390/biomedicines11010139 [doi] LID - 139 AB - 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. FAU - Valenzuela, Ignacio AU - Valenzuela I AUID- ORCID: 0000-0002-7277-2152 AD - Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium. FAU - Zapletalova, Katerina AU - Zapletalova K AD - Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium. AD - Third Faculty of Medicine, Institute for the Care of Mother and Child, Charles University, 147 10 Prague, Czech Republic. FAU - Greyling, Marnel AU - Greyling M AD - Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium. FAU - Regin, Yannick AU - Regin Y AD - Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium. FAU - Gie, Andre AU - Gie A AD - Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University and Tygerberg Hospital, Cape Town 7505, South Africa. FAU - Basurto, David AU - Basurto D AUID- ORCID: 0000-0002-2022-9027 AD - Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium. FAU - Deprest, Jan AU - Deprest J AD - Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium. AD - Department of Obstetrics and Gynecology, Division Woman and Child, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. FAU - van der Merwe, Johannes AU - van der Merwe J AUID- ORCID: 0000-0002-1381-4033 AD - Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium. AD - Department of Obstetrics and Gynecology, Division Woman and Child, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. LA - eng GR - 765274/European Union's Horizon 2020 research and innovation programme/ PT - Journal Article DEP - 20230105 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC9855731 OTO - NOTNLM OT - animal model OT - fetal growth restriction OT - lung development OT - neurodevelopment OT - placental insufficiency OT - preclinical OT - prematurity OT - rabbit COIS- The authors declare no conflict of interest. EDAT- 2023/01/22 06:00 MHDA- 2023/01/22 06:01 PMCR- 2023/01/05 CRDT- 2023/01/21 01:13 PHST- 2022/12/06 00:00 [received] PHST- 2022/12/26 00:00 [revised] PHST- 2022/12/29 00:00 [accepted] PHST- 2023/01/21 01:13 [entrez] PHST- 2023/01/22 06:00 [pubmed] PHST- 2023/01/22 06:01 [medline] PHST- 2023/01/05 00:00 [pmc-release] AID - biomedicines11010139 [pii] AID - biomedicines-11-00139 [pii] AID - 10.3390/biomedicines11010139 [doi] PST - epublish SO - Biomedicines. 2023 Jan 5;11(1):139. doi: 10.3390/biomedicines11010139.