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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