402: The role of NADPH oxidase enzymes in fetal alcohol syndrome

Abstract

in fetal alcohol syndrome Alexandria Hill, Huazhi Yin, Ester Tamayo, Nathan Drever, George Saade, Egle Bytautiene University of Texas Medical Branch, Maternal-Fetal Medicine, Galveston, TX, Scott & White Healthcare, Maternal-Fetal Medicine, Temple, TX OBJECTIVE: Fetal alcohol syndrome (FAS) is the most common cause of non-genetic preventable neurocognitive disability. Oxidative stress is one of the purported mechanisms. NADPH oxidase (NOX) is an enzyme that is involved in the production of reactive oxygen species (ROS). Our objective was to determine whether the NOX enzyme system is involved in FAS. STUDY DESIGN: A well-validated FAS animal model was used (Spong, et al). Timed, pregnant C57BL6/J mice were treated on gestational day 8 with a 0.03ml/g intraperitoneal injection of either 25% alcohol or saline. On gestational day 18, the mice were euthanized and fetuses removed. Fetal brains, livers, and placenta were collected for mRNA extraction (n 20 in each group) and quantitative real-time PCR of NOX subunits (DUOX1, DUOX2, NOX1, NOX2, NOX3, NOX4, NOXA1, NOXO1, RAC1, p22phox, and p67phox) was performed. Groups were compared using Student’s t or Mann-Whitney test as appropriate (statistical significance: p 0.05). RESULTS: NOX subunits DUOX2, NOXA1, and NOXO1 were significantly upregulated in the fetal brain in the ethanol group compared with control (Figure). The other subunits NOX1-4, DUOX1, and p67phox were also upregulated in the alcohol group, but the difference did not reach significance. NOXA1 was downregulated in the placenta and p67phox was upregulated in the liver of alcohol exposed pups. There were no differences between alcohol and control in any of the other NOX subunits in the liver or placenta. CONCLUSION: The NOX enzyme system is upregulated in the brain of fetuses exposed to alcohol. This effect is specific to the brain. NOX enzymes appear to be central to the generation of brain ROS in FAS. These results identify the NOX system as a potential target for preventative approaches in FAS.