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A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo
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 o...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists Ltd
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770145/ https://www.ncbi.nlm.nih.gov/pubmed/26744353 http://dx.doi.org/10.1242/dmm.022012 |
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author | Zhang, Shi-Jie Li, Yi-Fang Tan, Rui-Rong Tsoi, Bun Huang, Wen-Shan Huang, Yi-Hua Tang, Xiao-Long Hu, Dan Yao, Nan Yang, Xuesong Kurihara, Hiroshi Wang, Qi He, Rong-Rong |
author_facet | Zhang, Shi-Jie Li, Yi-Fang Tan, Rui-Rong Tsoi, Bun Huang, Wen-Shan Huang, Yi-Hua Tang, Xiao-Long Hu, Dan Yao, Nan Yang, Xuesong Kurihara, Hiroshi Wang, Qi He, Rong-Rong |
author_sort | Zhang, Shi-Jie |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4770145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The Company of Biologists Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-47701452016-03-07 A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo Zhang, Shi-Jie Li, Yi-Fang Tan, Rui-Rong Tsoi, Bun Huang, Wen-Shan Huang, Yi-Hua Tang, Xiao-Long Hu, Dan Yao, Nan Yang, Xuesong Kurihara, Hiroshi Wang, Qi He, Rong-Rong Dis Model Mech Research Article 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. The Company of Biologists Ltd 2016-02-01 /pmc/articles/PMC4770145/ /pubmed/26744353 http://dx.doi.org/10.1242/dmm.022012 Text en © 2016. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Zhang, Shi-Jie Li, Yi-Fang Tan, Rui-Rong Tsoi, Bun Huang, Wen-Shan Huang, Yi-Hua Tang, Xiao-Long Hu, Dan Yao, Nan Yang, Xuesong Kurihara, Hiroshi Wang, Qi He, Rong-Rong A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo |
title | A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo |
title_full | A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo |
title_fullStr | A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo |
title_full_unstemmed | A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo |
title_short | A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo |
title_sort | new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of pax6 in the chick embryo |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4770145/ https://www.ncbi.nlm.nih.gov/pubmed/26744353 http://dx.doi.org/10.1242/dmm.022012 |
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