title: Prolonging in utero-like oxygenation after birth diminishes oxidative stress in the lung and brain of mice pups.
abstract: BACKGROUND
  Fetal-to-neonatal transition is associated with oxidative stress. In preterm infants, immaturity of the antioxidant system favours supplemental oxygen-derived morbidity and mortality.
  
  
  OBJECTIVE
  To 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.
  
  
  METHODS
  Inspiratory 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.
  
  
  RESULTS
  As 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.
  
  
  CONCLUSIONS
  Delaying 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.
authors.affiliation: Neonatal Research Group, Health Research Institute, Hospital La Fe, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escobar
authors.forename: Elena
authors.initials: E
authors.lastname: Cubells
authors.forename: Masahiro
authors.initials: M
authors.lastname: Enomoto
authors.forename: Guillermo
authors.initials: G
authors.lastname: Quintás
authors.forename: Julia
authors.initials: J
authors.lastname: Kuligowski
authors.forename: Cristina Martinez
authors.initials: CM
authors.lastname: Fernández
authors.forename: Isabel
authors.initials: I
authors.lastname: Torres-Cuevas
authors.forename: Juan
authors.initials: J
authors.lastname: Sastre
authors.forename: Jaques
authors.initials: J
authors.lastname: Belik
authors.forename: Máximo
authors.initials: M
authors.lastname: Vento
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism*; D015687:Cell Hypoxia; D005260:Female; D005786:Gene Expression Regulation; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000235:genetics; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D018384:Oxidative Stress; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000235:genetics; D011247:Pregnancy; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005979:Glutathione Peroxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C000597536:Noq1 protein, mouse; D050862:Oxidoreductases Acting on Sulfur Group Donors; C529381:sulfiredoxin protein, mouse; D005978:Glutathione; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse
keywords: CySH, L-cysteine; CyS–NEM, cysteine covalently bonded to N-ethylmaleimide; Fetal-to-neonatal transition; FiO2, inspiratory oxygen fraction; G18, 18th day of gestation; GCL, glutamylcysteine ligase; GSH, reduced glutathione; GSSG, oxidized glutathione; GS–NEM, reduced glutathione covalently bonded to N-ethylmaleimide; Glutathione; LC–MS/MS, liquid chromatography coupled to tandem mass spectrometry; NEM, N-ethylmaleimide; O14, hypoxia group (FiO2=14%); O21, normoxia group (FiO2=21%); Oxidative stress; Oxygen; P1, 24 h after birth; P7, 1 week after birth; Redox regulation; SpO2, oxygen saturation; g6pdx, glucose 6 phosphate dehydrogenase gene; gapdh, glyceraldehyde-3-phosphate dehydrogenase gene; gclm, glutamylcysteine ligase modifier subunit gene; gpx1, glutathione peroxidase 1 gene; gsr, glutathione reductase gene; m/z, mass-to-charge ratio; me1, malic enzyme 1 gene; noq1, NAD(P)H:quinone oxidoreductase 1; paO2, partial pressure of oxygen; pgd, phosphogluconate dehydrogenase gene; srnx1, sulfiredoxin 1 gene; trxnd1, thioredoxin reductase 1 gene; γ-GC, gamma-glutamyl cysteine; γ-GC–NEM, gamma-glutamyl cysteine covalently bonded to N-ethylmaleimide
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