Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat

High sucrose low copper diet in pregnant diabetic rats induces transient oxidative stress, hypoxia, and apoptosis in the offspring's liver

“…The weight of the CDs offspring was reduced compared to the Sabra rats during the first postnatal week, with some differences between those fed HSD and those fed RD. Reduced fetal weight at term of the CDs compared to Sabra rats, especially those from dams fed HSD was found by us previously (Ergaz et al, ; Ornoy et al, ). Since at PND 30 males already tend to be heavier, we discriminated between the genders.…”

“…We previously found in these animals that maternal diabetes decreased fetal growth on day 21 of gestation (at term) and enhanced oxidative stress in the fetal liver and brain as well as in the placenta (Ornoy et al, ). Antioxidants given to the dams alleviated the oxidative stress in the term fetuses but did not normalize fetal growth, which was normalized only after increasing the food copper concentrations (Ergaz et al, ; Ornoy et al, ). In the pancreas of these 21‐day old fetuses, we found increased oxidative stress, increased apoptosis and proliferation and decreased insulin secretion (Ergaz et al, ).…”

Diabetes in the Cohen Rat Intensifies the Fetal Pancreatic Damage Induced by the Diabetogenic High Sucrose Low Copper Diet

“…The global DNA hypomethylation induced by diabetogenic diet was also found in placentas of the Cohen diabetic sensitive fed diabetogenic diet (Ergaz et al., ). Other studies showed DNA hypomethylation in type 1 (Fradin et al., ) and type 2 (Liu et al., ) diabetes, or DNA hypermethylation only in type 2 diabetes (Barres et al., ).…”

“…We have no explanation for the different effect of copper supplementation on catalase and catalase‐like activity in the different strains; however, this was also shown in the placenta in which we found increased catalase and catalase‐like activity in the fetuses of dams of both strains fed diabetogenic diet. Copper supplementation further increased in the Sabra and decreased in the Cohen diabetic sensitive catalase and catalase‐like activity (Ergaz et al., ). In our previous studies, we found in adult rats that catalase and catalase‐like activity were significantly increased in the pancreas of Cohen diabetic sensitive fed diabetogenic diet (Ryu et al., ) with a direct correlation between catalase and catalase‐like activity and catalase gene expression.…”

“…However, growth restriction and oxidative stress was also induced in the control, nondiabetic rats while on the same diet (Ergaz et al., ). The antioxidants vitamins C and E (Ornoy et al., ) or Tempol (Ergaz et al., ) reduced fetal oxidative stress but without recovery of the growth restriction. On the other hand, copper supplementation reduced the degree of maternal hyperglycemia and normalized fetal growth and oxidative stress parameters (Ergaz et al., ).…”