Hyperglycemia slows embryonic growth and suppresses cell cycle via cyclin D1 and p21

Devon E Scott-Drechsel1, Sandra Rugonyi, Daniel L Marks

  • 1Biomedical Engineering Department, Oregon Health & Science University, Portland, Oregon, USA.

Diabetes
|November 30, 2012
PubMed

Insights

High blood sugar during pregnancy significantly increases the risk of fetal heart defects. This study shows hyperglycemia in chick embryos slows cell growth, potentially causing these developmental issues.

Area of Science:

  • Developmental biology
  • Endocrinology
  • Cardiovascular science

Background:

  • Diabetes in pregnancy elevates fetal risk for cardiac malformations due to hyperglycemia and osmotic stress.
  • Understanding the mechanisms linking maternal hyperglycemia to embryonic heart development is crucial.

Purpose of the Study:

  • To investigate the impact of pulsed and sustained hyperglycemia on early heart development in chick embryos.
  • To identify cellular and molecular changes associated with hyperglycemia-induced developmental delays.

Main Methods:

  • Two models of hyperglycemia were used: pulsed (daily glucose) and sustained (single yolk injection).
  • Embryo size, mortality, and development were assessed.
  • Gene expression of glucose transporter GLUT1 and cell cycle regulators (p21, cyclin D1) were analyzed.
  • Cell proliferation in the heart outflow tract was quantified.

Main Results:

  • Both hyperglycemia models reduced embryo size, increased mortality, and delayed development.
  • Sustained hyperglycemia decreased GLUT1 expression and led to hyperosmolarity.
  • Reduced proliferation of myocardial and endocardial cells was observed in the sustained model.
  • Sustained hyperglycemia increased the cell cycle inhibitor p21 and decreased the promoter cyclin D1.

Conclusions:

  • Hyperglycemia-induced developmental delays are linked to slowed cell cycle progression and reduced cellular proliferation.
  • These cellular changes may underlie the cardiac defects observed in fetuses of diabetic mothers.
  • The study provides insights into the mechanisms of diabetic embryopathy affecting heart development.

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