Maternal diabetes in vivo and high glucose concentration in vitro increases apoptosis in rat embryos

Reprod Toxicol. 2007 Jan;23(1):63-74. doi: 10.1016/j.reprotox.2006.08.009. Epub 2006 Sep 1.


Apoptosis may be involved in diabetes-induced embryonic dysmorphogenesis. We estimated the occurrence of apoptosis in embryos of a rat model for diabetic pregnancy. We found decreased Bcl-2, increased Bax and cleaved Caspase 3 proteins in embryos from diabetic rats. Moreover, we found increased activation of Caspase 3 in cells from embryos previously exposed to a diabetes-like environment (in vivo, in vitro) compared to cells from control embryos, which was normalized by supplementation of N-acetylcysteine or apoptosis inhibitor. We detected increased propidium iodide uptake in embryonic cells exposed to maternal diabetes, a finding confirmed by vital staining. Additionally, we found increased dysmorphogenesis in embryos exposed to a diabetic environment in vivo and in vitro. Exposure to a diabetic milieu during organogenesis increases apoptosis in embryonic cells and dysmorphogenesis in embryos. Enhanced apoptotic rate may have a role in diabetic embryopathy by inducing disturbed embryonic maturation, increased rates of resorptions and congenital malformations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Drug-Induced*
  • Animals
  • Apoptosis* / drug effects
  • Apoptosis* / physiology
  • Caspase 3 / metabolism
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Experimental / pathology
  • Embryo, Mammalian / abnormalities
  • Embryo, Mammalian / drug effects
  • Embryo, Mammalian / metabolism
  • Embryonic Development / drug effects*
  • Embryonic Development / physiology
  • Female
  • Fluorescent Antibody Technique, Indirect
  • Glucose / pharmacology*
  • Immunoenzyme Techniques
  • Organ Culture Techniques
  • Pregnancy
  • Pregnancy in Diabetics / metabolism*
  • Pregnancy in Diabetics / pathology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2-Associated X Protein / metabolism


  • Bax protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Caspase 3
  • Glucose