title: Effects of 2,5-hexanedione on angiogenesis and vasculogenesis in chick embryos.
abstract: n-Hexane is widely used in industry and its metabolite, 2,5-hexanedione (2,5-HD), has been implicated as a neural toxin in the developing fetus. Using the chick embryo model, we have previously revealed the neurotoxicity of 2,5-HD during development and established that high dose of 2,5-HD was embryo lethal. In view of the close linkage in biology for neurogenesis and angiogenesis, we speculated that it was most likely caused by cardiovascular dysplasia, therefore in this study, we investigated the effects of 2,5-HD on the development of the vasculature, which involves vasculogenesis and angiogenesis. Using gastrulating chick embryos as a model, we demonstrated that the hemangioblasts (precursor of hematopoietic and endothelial cells) migrated to the area opaca where they form the blood islands. However, this process was impaired when the embryos were treated with 2,5-HD, suggesting that 2,5-HD is capable of impairing vasculogenesis. To study the effect of 2,5-HD exposure on angiogenesis, we used the chick yolk-sac membrane (YSM) and chorioallantoic membrane (CAM) models. We found that, at low (0.02M) concentration, 2,5-HD stimulated angiogenesis while at higher concentrations (>0.1M) it inhibited this process. This biphasic response of angiogenesis to 2,5-HD exposure was found to be associated with altered expression of the VEGF-R, FGF-2 and angiogenin. Moreover, we also determined that 2,5-HD exposure increased the reactive oxygen species (ROS) production. In conclusion, 2,5-HD could induce dysplasia in the developing vasculature, which in turn could cause extravascular hemolysis and the embryos to die.
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Luo
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: wangguang7453@126.com.
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 510632, China.
authors.forename: Chang-Jun
authors.initials: CJ
authors.lastname: Xu
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Ren-Hao
authors.initials: RH
authors.lastname: Yang
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: E
authors.initials: E
authors.lastname: Ding
authors.affiliation: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Yan-Qing
authors.initials: YQ
authors.lastname: He
authors.affiliation: Division of Cell and Developmental Biology, University of Dundee, Dundee DD1 5EH, 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: Division of Histology and Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D015820:Cadherins / Q000235:genetics; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D006588:Hexanones / Q000633:toxicity*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000235:genetics; D015017:Yolk Sac / Q000098:blood supply / Q000187:drug effects; D000099152:Cadherin 5
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D016222:Fibroblast Growth Factor 2; D006588:Hexanones; D009498:Neurotoxins; D011505:Protein-Tyrosine Kinases; D017382:Reactive Oxygen Species; D012259:Ribonuclease, Pancreatic; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3; D000099152:Cadherin 5; C011269:2,5-hexanedione; C046366:angiogenin
keywords: 2,5-Hexanedione; Angiogenesis; Blood islands; Chick embryos; Vasculogenesis