Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups

•The present study describes a mouse model meant to study redox biology of the fetal-to-neonatal transition under hypoxia.•Lung protection against oxidative stress was induced at day 1 after birth.•Improvement in lung and brain redox environments 7 days after birth was observed.•Changes detected in lung and brain were subtle, however significant, under physiologic conditions.•The applicability of our model under pathophysiologic conditions (e.g. postnatal hyperoxia) should be tested.

BackgroundFetal-to-neonatal transition is associated with oxidative stress. In preterm infants, immaturity of the antioxidant system favours supplemental oxygen-derived morbidity and mortality.ObjectivesTo assess if prolonging in utero-like oxygenation during the fetal-to-neonatal transition limits oxidative stress in the lung and brain, improving postnatal adaptation of mice pups.Material and methodsInspiratory oxygen fraction (FiO2) in pregnant mice was reduced from 21% (room air) to 14% (hypoxia) 8–12 h prior to delivery and reset to 21% 6–8 h after birth. The control group was kept at 21% during the procedure. Reduced (GSH) and oxidized (GSSG) glutathione and its precursors [γ-glutamyl cysteine (γ-GC) and L-cysteine (CySH)] content and expression of several redox-sensitive genes were evaluated in newborn lung and brain tissue 1 (P1) and 7 (P7) days after birth.ResultsAs compared with control animals, the GSH/GSSG ratio was increased in the hypoxic group at P1 and P7 in the lung, and at P7 in the brain. In the hypoxic group a significant increase in the mRNA levels of NAD(P)H:quinone oxidoreductase 1 (noq1), Sulfiredoxin 1 (srnx1) and Glutathione Peroxidase 1 (gpx) was found in lung tissue at P1, as well as a significant increase in gpx in brain tissue at P7.ConclusionsDelaying the increase in tissue oxygenation to occur after birth reduces short-and-long-term oxidative stress in the lung. Similar yet more subtle effects were found in the brain. Apparently, the fetal-to-neonatal transition under hypoxic conditions appears to have protective qualities.

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