In ovo hyperglycemia causes congenital limb defects in chicken embryos via disruption of cell proliferation and apoptosis

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1866

Article

Ding, Zehuan¹  Zhou, Huijuan³  McCauley, Naomi¹  Ko, Gladys²  Zhang, Ke K.^1,4  Xie, Linglin¹ 

[1] Texas A&M Univ, Dept Nutr, College Stn, TX 77843 USA

[2] Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA

[3] Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA

[4] Texas A&M Univ, Coll Med, Ctr Epigenet & Dis Prevent, Inst Biosci & Technol, Houston, TX USA

关键词: Hyperglycemia;    Cardiovascular defect;    Limb defect;    Apoptosis;    Proliferation;    Shh-signaling;   

DOI  :  10.1016/j.bbadis.2020.165955

来源: Elsevier

【 摘 要 】

While the correlation between diabetes during pregnancy and birth defects is well-established, how hyperglycemia causes developmental abnormalities remains unclear. In this study, we developed a novel hyperglycemic chicken embryonic model by administrating various doses of glucose to fertilized eggs at embryonic stages HH16 or HH24. When the embryos were collected at HH35, the LD50 was 1.57 g/Kg under HH16 treatment and 0.93 g/Kg under HH24 treatment, indicating that hyperglycemic environments can be lethal for the embryos. When exposed to a dose equal to or higher than 1 g/Kg glucose at HH16 or HH24, more than 40% of the surviving chicken embryos displayed heart defects and/or limb defects. The limb defects were associated with proliferation defects of both the wing and leg buds indicated by reduced numbers of p-H3S10 labeled cells. These limb defects were also associated with ectopic apoptosis in the leg bud and expression changes of key apoptotic genes. Furthermore, glucose treatment induced decreased expression of genes involved in Shh-signaling, chondrogenesis, and digit patterning in the limb bud. In summary, our data demonstrated that a highglucose environment induces congenital heart and limb defects associated with disrupted cell proliferation and apoptosis, possibly through depressed Shh-signaling.

【 授权许可】

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