The role of NADPH oxidase in a mouse model of fetal alcohol syndrome

Alexandria J. Hill, Nathan Drever, Huaizhi Yin, Esther Tamayo, George Saade, Egle Bytautiene

Research output: Contribution to journalArticle

12 Scopus citations

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. Study Design 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. Conclusion 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.

Original languageEnglish (US)
JournalAmerican Journal of Obstetrics and Gynecology
Volume210
Issue number5
DOIs
StatePublished - 2014

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Keywords

  • fetal alcohol syndrome
  • nicotinamide adenine dinucleotide phosphate oxidase
  • reactive oxygen species

ASJC Scopus subject areas

  • Obstetrics and Gynecology

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