Valenzuela Ignacio, Zapletalova Katerina, Greyling Marnel, Regin Yannick, Gie Andre, Basurto David, Deprest Jan, van der Merwe Johannes
Cluster Woman and Child, Department of Development and Regeneration, Group Biomedical Sciences, KU Leuven Herestraat 49, 3000 Leuven, Belgium.
Third Faculty of Medicine, Institute for the Care of Mother and Child, Charles University, 147 10 Prague, Czech Republic.
Biomedicines. 2023 Jan 5;11(1):139. doi: 10.3390/biomedicines11010139.
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.
我们之前报道了胎盘灌注不足诱导的胎儿生长受限在近足月出生兔从新生儿早期直至青春期前的多系统后遗症。在此，我们描述早产兔中胎儿生长受限对肺和神经发育的影响。我们假设胎儿生长受限在肺功能和神经发育方面对早产有额外的有害影响。在妊娠第25天通过胎盘灌注不足诱导胎儿生长受限，方法是在一个子宫角进行部分子宫胎盘血管结扎。在妊娠第29天通过剖宫产分娩兔子，并采集胎盘进行组织学检查。新生兔在出生后第1天进行神经行为或肺功能评估，随后分别采集脑或肺。神经发育评估包括神经行为测试以及脑内细胞密度和凋亡的多区域定量分析。肺评估包括功能测试、肺泡形态计量学和气道组织学检查。与对照组相比，胎儿生长受限与围产期死亡率更高、出生体重和胎盘重量更低以及脑体重比相似有关。胎盘灌注不足使胎儿生长受限组胎盘的迷路和交界区体积减小。胎儿生长受限损害肺功能，表现为实质阻力、阻尼和弹性增加。两组间肺泡形态计量学和气道平滑肌含量相当。神经行为测试显示胎儿生长受限兔存在运动和感觉功能损害。在胎儿生长受限组的脑中，细胞密度总体降低，特定区域凋亡增加。总之，在早产兔中，胎盘灌注不足导致更高的死亡率、胎儿生长受限以及早期评估中肺和脑发育受损。本研究补充了该模型中近足月出生兔胎盘、肺和神经发育受损的先前研究结果。
