The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

Ergaz, Zivanit; Shoshani-Dror, Dana; Guillemin, Claire; Neeman-azulay, Meytal; Fudim, Liza; Weksler-Zangen, Sarah; Stodgell, Christopher J.; Miller, Richard K.; Ornoy, Asher

doi:10.1016/j.taap.2012.10.006

Cited by 10 publications

(16 citation statements)

References 54 publications

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“…The Cohen diabetic sensitive fetuses had significantly more intense immunostaining for NFκB and HIF1‐α in their pancreas compared to the Sabra fetuses regardless of the diet. The current data are in accordance with our previous findings that embryos cultured in a hyperglycemic culture medium (Ornoy et al., ) and mature fetal liver of the Cohen diabetic sensitive (Ergaz et al., ) had elevated HIF1‐α as a marker of hypoxia. Similar finding was observed by Bensellam et al.…”

Section: Discussionsupporting

confidence: 93%

“…The effect of the supplemented copper on the fetal pancreas may result from the improvement in maternal and subsequently fetal hyperglycemia and from the antioxidant effects of copper, as observed by us previously. We also found previously that 2 ppm of copper corrected the hypoglycemia and most oxidative stress parameters, but the fetuses were still copper deficient, implying that more copper is needed for a complete correction (Ergaz et al, 2012). Since our aim was to find the difference between normoglycemic and hyperglycemic state, we used the 1 ppm that was sufficient to partially correct the hyperglycemia.…”

Section: Discussionmentioning

confidence: 99%

“…The embryos and fetuses of the hyperglycemic Cohen Diabetic rats were growth restricted (Ornoy and Zusman, ), resembling women suffering from pregestational diabetes complicated by vasculopathy. 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.…”

Section: Introductionmentioning

confidence: 99%

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

Ergaz

Neeman-azulay

Weinstein-Fudim

et al. 2016

Birth Defects Research Pt B

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Intrauterine hyperglycemic environment could harm the fetus making it more susceptible to develop postnatal glucose intolerance. A possible mechanism is compromise of the fetal pancreatic development. We previously found that a high sucrose low copper diabetogenic diet induces type 2 diabetes in the Cohen diabetic sensitive rats, but not in the Sabra control rats. However, oxidative stress was observed in the placenta and term fetal liver of diabetic and nondiabetic controls. We now investigated whether the fetal pancreas is affected by this diet and whether the effects result from oxidative stress, maternal hyperglycemia, or both. Term fetal pancreases were evaluated for morphology, beta cells, oxidative stress, apoptosis, and DNA methylation. There were no microscopic changes in hematoxylin and eosin stained sections and beta cells immunostaining in the pancreas of fetuses of both strains. Fetuses of the sensitive strain fed diabetogenic diet had significantly higher activity of superoxide dismutase and catalase, elevated levels of low molecular weight antioxidants, and more intense immunostaining for nuclear factor kappa-B and hypoxia inducing factor-1␣. Both strains fed diabetogenic diet had increased immunostaining for Bcl-2-like protein and caspase 3 and decreased immunostaining for 5-methylcytosine in their islets and acini. Our data suggest that maternal diabetogenic diet alters apoptotic rate and epigenetic steady states in the term fetal pancreas, unrelated to maternal diabetes. Maternal hyperglycemia further increases pancreatic oxidative stress, aggravating the pancreatic damage. The diet-induced insults to the fetal pancreas may be an important contributor to the high susceptibility to develop diabetes following metabolic intrauterine insults.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Ergaz

Neeman-azulay

Weinstein-Fudim

et al. 2016

Birth Defects Research Pt B

Self Cite

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“…According to Cohen's original selection criteria, blood glucose levels (BGLs) at 2 hr of 180 mg/dl or above in the CDs were considered diabetic (Cohen, 1990). This was also described by us previously (Ergaz et al, 2012). All CDs rats fed HSD were diabetic at the beginning of the mating trials while the Sabra dams and the CDs fed RD were not (see in the results).…”

Section: Experimental Animalssupporting

confidence: 84%

“…In order to develop diabetes, the CDs are fed with a low copper diet. We previously showed that the oxidative stress in this model improved in 21 days old fetuses following the addition of copper to the drinking water of the copper deprived dams (Ergaz et al, ). Moreover, this was the main way to induce normalization of fetal growth.…”

Section: Discussionmentioning

confidence: 73%