Resveratrol prevents impairment in activation of retinoic acid receptors and MAP kinases in the embryos of a rodent model of diabetic embryopathy

Reprod Sci. 2012 Sep;19(9):949-61. doi: 10.1177/1933719112438972. Epub 2012 Apr 24.

Abstract

Diabetes induces impairments in gene expression during embryonic development that leads to premature and improper tissue specialization. Retinoic acid receptors (RARs and retinoid X receptor [RXRs]) and mitogen-activated protein kinases (MAPKs) play crucial roles during embryonic development, and their suppression or activation has been shown as a determinant of the fate of embryonic organogenesis. We studied the activation of RARs and MAPKs in embryonic day 12 (E12) in embryos of rats under normal, diabetic, and diabetic treated with resveratrol ([RSV]; 100 mg/kg body weight) conditions. We found downregulation of RARs and RXRs expressions as well as their DNA-binding activities in the embryos exhibiting developmental delays due to diabetes. Furthermore, the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2 was decreased and phosphorylation of c-Jun N-terminal kinase (JNK) 1/2 and p38 was increased. Interestingly, embryos of diabetic rats treated with RSV showed normalized patterns of RARs, RXRs, neuronal markers, and ERK, JNK and p38 phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Disease Models, Animal*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Fetal Diseases / drug therapy
  • Fetal Diseases / metabolism
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / metabolism
  • Neural Tube Defects / drug therapy*
  • Neural Tube Defects / metabolism
  • Pregnancy
  • Pregnancy in Diabetics / drug therapy*
  • Pregnancy in Diabetics / metabolism
  • Rats
  • Receptors, Retinoic Acid / antagonists & inhibitors*
  • Receptors, Retinoic Acid / metabolism
  • Resveratrol
  • Stilbenes / pharmacology
  • Stilbenes / therapeutic use*

Substances

  • Enzyme Inhibitors
  • Receptors, Retinoic Acid
  • Stilbenes
  • Mitogen-Activated Protein Kinases
  • Resveratrol