title: A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo.
abstract: Gestational diabetes mellitus (GDM) is one of the leading causes of fetal malformations. However, few models have been developed to study the underlying mechanisms of GDM-induced fetal eye malformation. In this study, a high concentration of glucose (0.2 mmol per egg) was injected into the air sac of chick embryos on embryo development day (EDD) 1 to develop a hyperglycemia model. Results showed that 47.3% of embryonic eye malformation happened on EDD 5. In this model, the key genes regulating eye development, Pax6, Six3 and Otx2, were downregulated by hyperglycemia. Among these genes, the expression of Pax6 was the most vulnerable to hyperglycemia, being suppressed by 70%. A reduction in Pax6 gene expression induced eye malformation in chick embryos. However, increased expression of Pax6 in chick embryos could rescue hyperglycemia-induced eye malformation. Hyperglycemia stimulated O-linked N-acetylglucosaminylation, which caused oxidative stress in chick embryos. Pax6 was found to be vulnerable to free radicals, but the antioxidant edaravone could restore Pax6 expression and reverse eye malformation. These results illustrated a successful establishment of a new chick embryo model to study the molecular mechanism of hyperglycemia-induced eye malformation. The suppression of the Pax6 gene is probably mediated by oxidative stress and could be a crucial target for the therapy of GDM-induced embryonic eye malformation.
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Shi-Jie
authors.initials: SJ
authors.lastname: Zhang
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Yi-Fang
authors.initials: YF
authors.lastname: Li
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Rui-Rong
authors.initials: RR
authors.lastname: Tan
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Bun
authors.initials: B
authors.lastname: Tsoi
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Wen-Shan
authors.initials: WS
authors.lastname: Huang
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Tang
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Hu
authors.affiliation: Guangdong Research Institute of Traditional Chinese Medicine Manufacturing Technology, Guangzhou 510095, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Yao
authors.affiliation: Division of Histology & Embryology, Key Laboratory for Regenerative Medicine of the Ministry of Education, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Yang
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Anti-stress and Health Research Center, College of Pharmacy, Jinan University, Guangzhou 510632, China rongronghe@jnu.edu.cn.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: He
mesh_terms: D000818:Animals; D002642:Chick Embryo; D016640:Diabetes, Gestational / Q000378:metabolism*; D004195:Disease Models, Animal; D005124:Eye Abnormalities / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006943:Hyperglycemia / Q000235:genetics; D018384:Oxidative Stress; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics*; D010957:Plasmids; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins
keywords: Chick embryo; Eye malformation; Hyperglycemia; Oxidative stress; Pax6