Circadian clock activity in human umbilical vein endothelial cells of preterm and term neonates

Abstract

Background During mammalian gestation, fetal circadian rhythms are thought to be mainly controlled by maternal signals. In humans, the initiation and activity of central and peripheral circadian clocks is largely unknown. This study aimed to elucidate the developmental clock properties in human umbilical vein endothelial cells (HUVECs). Methods HUVECs were obtained from (a) preterm infants, subgrouped according to birth weight or gestational age classification, and (b) term infants (in total: n = 60). In vitro clock activity was determined by using live bioluminescence recording of a luciferase reporter gene under circadian control over 120 h. In addition, core clock and clock-associated gene expression were quantified using NanoString technology. Results Peripheral clock activity was detected, regardless of prematurity and birth weight classification. The mean period, amplitude, and phase of circadian oscillations were not significantly associated with gestational age or birth weight classification. Conclusions Peripheral clock activity can be demonstrated in HUVECs from both preterm and term infants without significant developmental differences in the period, amplitude, and phase of oscillations. This model may be useful to identify perturbation factors of proper development and entrainment of neonatal circadian clock activity. Impact We established a model system for analyzing the peripheral clock in preterm and term HUVECs. In HUVECs, the peripheral clock exhibits functional in vitro activity independent of gestational age or birth weight categories. In this model system, neither significant developmental differences exist in the period, amplitude, and phase, nor in the expression of circadian core clock and clock-associated genes. Entrainment and proper function of the circadian clock deserve attention in neonatal intensive care.