Angiogenesis is repressed by ethanol exposure during chick embryonic development
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- 作者：Guang Wang ; Shan Zhong ; Shi-yao Zhang ; Zheng-lai Ma ; Jian-long Chen ; Wen-hui Lu ; Xin Cheng ; Manli Chuai ; Kenneth Ka Ho Lee ; Da-xiang Lu and Xuesong Yang
- 关键词：ethanol ; angiogenesis ; chick embryo ; yolk sac membrane ; ROS
- 刊名：Journal of Applied Toxicology
- 出版年：2016
- 出版时间：May 2016
- 年：2016
- 卷：36
- 期：5
- 页码：692-701
- 全文大小：735K
- ISSN：1099-1263
文摘
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. Copyright