AbstractGrowth in the immediate postnatal period for extremely low birth weight (ELBW, birth weight < 1000 g) infants is an important topic in neonatal medicine. The goal is to ensure adequate postnatal growth and to minimize complications resulting from suboptimal growth. Past efforts have focused on postnatal nutrition as well as on minimizing comorbidities. It has not been systematically assessed whether antenatal factors play a role in postnatal growth. In this report, we conducted a retrospective study on 91 maternal–neonatal pairs. We prospectively collected maternal and neonatal demographic data, neonatal nutrition in the first 7 days of life and after enteral nutrition is fully established, comorbidity data, as well as weight data from birth to 50 weeks corrected gestational age. We developed a linear mixed-effects model to examine the role of placental insufficiency, as defined by fetal Doppler studies, in postnatal weight z-score trajectory over time in the ELBW population. We relied on Akaike Information Criterion (AIC) and Bayesian Information Criterion (BIC) for model selection. Interestingly, the selected model included a quadratic term of time and a placental insufficiency-by-time interaction term. In a covariate analysis, AIC and BIC both favored a model that included calories intake in the first 7 days of life and the total duration of antibiotics as fixed-effects, but not their interaction terms with time. Overall, we demonstrated for the first time that placental insufficiency, an antenatal factor, is a major determinant of postnatal weight trajectory in the ELBW population. Prospective studies are warranted to confirm our findings.

Individuals with intrauterine growth restriction (IUGR) are at an increased risk for neurodevelopmental impairment. Fetal cortical neurogenesis is a time-sensitive process in which fetal neural stem cells (NSCs) follow a distinct pattern of layer-specific neuron generation to populate the cerebral cortex. Here, we used a murine maternal hypoxia-induced IUGR model to study the impact of IUGR on fetal NSC development. In this model, timed-pregnant mice were exposed to hypoxia during the active stage of neurogenesis, followed by fetal brain collection and analysis. In the IUGR fetal brains, we found a significant reduction in cerebral cortical thickness accompanied by decreases in layer-specific neurons. Using EdU labeling, we demonstrated that cell cycle progression of fetal NSCs was delayed, primarily observed in the G2/M phase during inward interkinetic nuclear migration. Following relief from maternal hypoxia exposure, the remaining fetal NSCs re-established their neurogenic ability and resumed production of layer-specific neurons. Surprisingly, the newly generated neurons matched their control counterparts in layer-specific marker expression, suggesting preservation of the fetal NSC temporal identity despite IUGR effects. As expected, the absolute number of neurons generated in the IUGR group remained lower compared to that in the control group due to a reduced fetal NSC pool size as a result of cell cycle defect. Transcriptome analysis identified genes related to energy expenditure and G2/M cell cycle progression being affected by maternal hypoxia-induced IUGR. Taken together, maternal hypoxia-induced IUGR is associated with a defect in cell cycle progression of fetal NSCs, and has a long-term impact on offspring cognitive development.

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Cell motility has been extensively studied in in vitro models using fibroblasts and keratocytes, but the cell type-specific mechanisms underlying migration of lineage-or disease-specific cells, such as neural and glial progenitor cells, remain an active field for investigation. The migrating neural and glial progenitor cells contribute to the development, tissue repair and tumor invasion in the central nervous system (CNS). Cell migration is a highly dynamic process which relies on membranous protrusions to assemble, extend, disassemble and retract. In the CNS, the motility of neural and glial progenitor cells is affected by various cell-autonomous and non-cell-autonomous mechanisms such as signaling molecules, actin and microtubule interactions, and environmental cues. Here, we described a live-cell migration assay for use in the assessment of neural and glial progenitor cell migration. We first will demonstrate the procedures for isolating and culturing neural and glial progenitor cells. Next, we will demonstrate the acquisition of time-lapse images using phase contrast microscopy, the methods for quantification and the analyses of various motility parameters including speed, velocity, straightness and leading-edge dynamics. This method allows researchers to dissect the mechanisms of cell motility in response to different environmental cues, such as chemoattractive and repulsive signals, matrix adhesiveness and stiffness. This assay also allows researchers to study migration of pharmacologically and genetically manipulated cells.