A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo.
A new gestational diabetes mellitus model: hyperglycemia-induced eye malformation via inhibition of Pax6 in the chick embryo.
复制标题
一种新的妊娠糖尿病模型，通过抑制鸡胚中的 Pax6 导致高血糖引起的眼睛畸形
DOI：
10.1242/dmm.022012
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发表时间：
2016-02
影响因子：
4.3
通讯作者：
He RR
中科院分区：
文献类型：
--
作者：
Zhang SJ;Li YF;Tan RR;Tsoi B;Huang WS;Huang YH;Tang XL;Hu D;Yao N;Yang X;Kurihara H;Wang Q;He RR
妊娠糖尿病（GDM）是导致胎儿畸形的主要原因之一。然而，很少有模型已被开发来研究GDM诱导的胎儿眼畸形的潜在机制。在本研究中，高浓度葡萄糖（0.2 mmol/蛋）注射到鸡胚胎发育第1天（EDD）的气囊中，建立高血糖模型。 结果表明：47.3%的胚胎眼畸形发生在EDD 5.在该模型中，调节眼睛发育的关键基因Pax 6、Six 3和Otx 2被高血糖下调。在这些基因中，Pax 6的表达最容易受到高血糖的影响，被抑制了70%。Pax 6基因表达降低导致鸡胚眼畸形。然而，Pax 6在鸡胚中的表达增加可以挽救高血糖诱导的眼畸形。高血压刺激O-连接的N-乙酰氨基葡萄糖，这导致鸡胚的氧化应激。Pax 6被发现易受自由基的影响，但抗氧化剂依达拉奉可以恢复Pax 6的表达并逆转眼畸形。本研究成功地建立了一种新的鸡胚模型，为进一步研究高血糖致眼畸形的分子机制奠定了基础。Pax 6基因的抑制可能是由氧化应激介导的，并且可能是治疗GDM诱导的胚胎眼畸形的关键靶点。总结：高血压通过氧化应激抑制Pax 6，并损害鸡胚的眼发育，一种新的妊娠糖尿病模型。
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. Summary: Hyperglycemia inhibited Pax6 via oxidative stress and impaired eye development in the chick embryo, a new gestational diabetes mellitus model.