title: The role of NADPH oxidase in a mouse model of fetal alcohol syndrome.
abstract: OBJECTIVE
  Fetal alcohol syndrome (FAS) is the most common cause of nongenetic mental retardation. Oxidative stress is one of the purported mechanisms. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is an enzyme involved in the production of reactive oxygen species. Our objective was to evaluate NOX in the fetal brain of a well-validated mouse model of FAS.
  
  
  METHODS
  Timed, pregnant C57BL/6J mice were injected intraperitoneally with 0.03 mL/g of either 25% ethyl alcohol or saline. Fetal brain, liver, and placenta were harvested on gestational day 18. The unit of analysis was the litter; tissue from 6-8 litters in the alcohol and control group was isolated. Evaluation of messenger ribonucleic acid (mRNA) expression of NOX subunits (DUOX1, DUOX2, NOX1, NOX2, NOX3, NOX4, NOXA1, NOXO1, RAC1, p22phox, and p67phox) was performed using quantitative real-time polymerase chain reaction; alcohol vs placebo groups were compared using a Student t test or a Mann-Whitney test (P < .05).
  
  
  RESULTS
  Alcohol exposed fetal brains showed significant up-regulation in subunits DUOX2 (1.61 ± 0.28 vs 0.84 ± 0.09; P = .03), NOXA1 (1.75 ± 0.27 vs 1.09 ± 0.06; P = .04), and NOXO1 (1.59 ± 0.10 vs 1.28 ± 0.05; P = .02). Differences in mRNA expression in the placenta were not significant; p67phox was significantly up-regulated in alcohol-exposed livers.
  
  
  CONCLUSIONS
  Various NOX subunits are up-regulated in fetal brains exposed to alcohol. This effect was not observed in the fetal liver or placenta. Given the available evidence, the NOX system may be involved in the causation of FAS through the generation of reactive oxygen species and may be a potential target for preventative treatment in FAS.
authors: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors: Alexandria J
authors: AJ
authors: Hill
authors: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors: Nathan
authors: N
authors: Drever
authors: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors: Huaizhi
authors: H
authors: Yin
authors: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors: Esther
authors: E
authors: Tamayo
authors: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors: George
authors: G
authors: Saade
authors: Department of Obstetrics and Gynecology, The University of Texas Medical Branch, Galveston, TX.
authors: Egle
authors: E
authors: Bytautiene
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000201:enzymology; D004195:Disease Models, Animal; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000201:enzymology* / Q000503:physiopathology; D005333:Fetus / Q000201:enzymology; D008810:Mice, Inbred C57BL; D009249:NADP; D019255:NADPH Oxidases / Q000502:physiology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D009249:NADP; D019255:NADPH Oxidases
keywords: fetal alcohol syndrome; nicotinamide adenine dinucleotide phosphate oxidase; reactive oxygen species