title: Angiogenesis is repressed by ethanol exposure during chick embryonic development.
abstract: It is now known that excess alcohol consumption during pregnancy can cause fetal alcohol syndrome to develop. However, it is not known whether excess ethanol exposure could directly affect angiogenesis in the embryo or angiogenesis being indirectly affected because of ethanol-induced fetal alcohol syndrome. Using the chick yolk sac membrane (YSM) model, we demonstrated that ethanol exposure dramatically inhibited angiogenesis in the YSM of 9-day-old chick embryos, in a dose-dependent manner. Likewise, the anti-angiogenesis effect of ethanol could be seen in the developing vessel plexus (at the same extra-embryonic regions) during earlier stages of embryo development. The anti-angiogenic effect of ethanol was found associated with excess reactive oxygen species (ROS) production; as glutathione peroxidase activity increased while superoxide dismutase 1 and 2 activities decreased in the YSMs. We further validated this observation by exposing chick embryos to 2,2'-azobis-amidinopropane dihydrochloride (a ROS inducer) and obtained a similar anti-angiogenesis effect as ethanol treatment. Semiquantitative reverse transcription-polymerase chain reaction analysis of the experimental YSMs revealed that expression of angiogenesis-related genes, vascular endothelial growth factor and its receptor, fibroblast growth factor 2 and hypoxia-inducible factor, were all repressed following ethanol and 2,2'-azobis-amidinopropane dihydrochloride treatment. In summary, our results suggest that excess ethanol exposure inhibits embryonic angiogenesis through promoting superfluous ROS production during embryo development.
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.|Department of Pathophysiology, Institute of Brain Research, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Guang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Shan
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Shi-yao
authors.initials: SY
authors.lastname: Zhang
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Zheng-lai
authors.initials: ZL
authors.lastname: Ma
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Jian-long
authors.initials: JL
authors.lastname: Chen
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Wen-hui
authors.initials: WH
authors.lastname: Lu
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Division of Cell and Developmental Biology, University of Dundee, Dundee, UK.
authors.forename: Manli
authors.initials: M
authors.lastname: Chuai
authors.affiliation: Key Laboratory for Regenerative Medicine of the Ministry of Education, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
authors.forename: Kenneth Ka Ho
authors.initials: KK
authors.lastname: Lee
authors.affiliation: Department of Pathophysiology, Institute of Brain Research, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Da-xiang
authors.initials: DX
authors.lastname: Lu
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000578:Amidines / Q000633:toxicity; D020533:Angiogenesis Inhibitors / Q000633:toxicity*; D000818:Animals; D002319:Cardiovascular System / Q000187:drug effects / Q000196:embryology; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004625:Embryo, Nonmammalian / Q000187:drug effects*; D047108:Embryonic Development / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D040262:Receptors, Vascular Endothelial Growth Factor / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D015017:Yolk Sac / Q000187:drug effects; D000099156:Superoxide Dismutase 2
chemical_list: D000578:Amidines; D020533:Angiogenesis Inhibitors; D000431:Ethanol; D016222:Fibroblast Growth Factor 2; D017382:Reactive Oxygen Species; D040262:Receptors, Vascular Endothelial Growth Factor; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D042461:Vascular Endothelial Growth Factor A; D000099156:Superoxide Dismutase 2; C046728:2,2'-azobis(2-amidinopropane)
keywords: ROS; angiogenesis; chick embryo; ethanol; yolk sac membrane