Author: Peng, Y.; Yang, P.-H.; Ng, S.S.M.; Lum, C.T.; Kung, H.-F.; Lin, M.C.
Description: Accumulated evidence indicates that maternal alcohol consumption causes fetal enteric damage and growth retardation. In this study, we investigated the underlying molecular mechanisms in a Xenopus model of fetal alcohol exposure. We established a condition of transient alcohol exposure that produces tadpoles with delayed gut maturation and decreased body length. We then investigated the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) by microinjecting plasmids expressing catalase and peroxiredoxin 5 (PRDX5) into two-cell stage embryos. Finally, the effects of these enzymes on the expression of key gut developmental genes were determined by animal cap explant assay. We showed that exposure of Xenopus embryos to 0.5% alcohol from stage 13 to stage 22 produced tadpoles with delayed gut maturation, reduced growth, and down-regulation in several gut developmental genes, with VegT, Pax6 and Sox17 most vulnerable. We further demonstrated that microinjection of catalase attenuated alcohol-induced ROS production and restored the expression of VegT and Pax6, but protected the embryos from delayed gut development and retarded growth only partially. By contrast, microinjection of PRDX5 reduced both ROS and RNS production, and prevented the gut and growth defects, and restored VegT, Pax6 and Sox17 gene expression. A positive correlation was found between delayed gut maturation and reduced body length. These results indicate the crucial roles of both the ROS-Pax6 and RNS-Sox17 signaling axes in alcohol-induced fetal gut defects and growth retardation. In addition, they suggest strongly a cause-and-effect relationship between alcohol-induced delayed gut maturation and growth retardation.
Subject headings: Animals; Antioxidants/metabolism; Biomarkers; Catalase/metabolism; Culture Techniques/methods; Digestive System/drug effects/embryology/growth & development; Embryo, Nonmammalian/anatomy & histology/drug effects; Ethanol/toxicity; Female; Gene Expression Regulation, Developmental/drug effects; Microinjections; Peroxidases/metabolism; Peroxiredoxins; Reactive Nitrogen Species/analysis/antagonists & inhibitors/metabolism; Reactive Oxygen Species/analysis/antagonists & inhibitors/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Xenopus laevis/embryology
Publication year: 2004
Journal or book title: Journal of Molecular Biology
Volume: 340
Issue: 4
Pages: 819-827
Find the full text : http://www.sciencedirect.com/science/article/pii/S0022283604006175
Find more like this one (cited by): https://scholar.google.com/scholar?cites=9977659846054035610&as_sdt=1000005&sciodt=0,16&hl=en
Type: Journal Article
Serial number: 1474