skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

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

Abstract

Fetal Growth Restriction (FGR) is a leading cause for long term morbidity. The Cohen diabetic sensitive rats (CDs), originating from Wistar, develop overt diabetes when fed high sucrose low copper diet (HSD) while the original outbred Sabra strain do not. HSD induced FGR and fetal oxidative stress, more prominent in the CDs, that was alleviated more effectively by copper than by the anti-oxidant vitamins C and E. Our aim was to evaluate the impact of copper or the anti-oxidant Tempol on placental size, protein content, oxidative stress, apoptosis and total DNA methylation. Animals were mated following one month of HSD or regular chow diet and supplemented throughout pregnancy with either 0, 1 or 2 ppm of copper sulfate or Tempol in their drinking water. Placental weight on the 21st day of pregnancy decreased in dams fed HSD and improved upon copper supplementation. Placental/fetal weight ratio increased among the CDs. Protein content decreased in Sabra but increased in CDs fed HSD. Oxidative stress biochemical markers improved upon copper supplementation; immunohistochemistry for oxidative stress markers was similar between strains and diets. Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. Placental global DNA methylation was decreasedmore » only among the CDs dams fed HSD. We conclude that FGR in this model is associated with smaller placentae, reduced DNA placental methylation, and increased oxidative stress that normalized with copper supplementation. DNA hypomethylation makes our model a unique method for investigating genes associated with growth, oxidative stress, hypoxia and copper. - Highlights: • Sensitive Cohen diabetic rats (CDs) had small placentae and growth restricted fetuses. • CDs dams fed high sucrose low copper diet had placental global DNA hypomethylation. • Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. • Oxidative stress parameters improved by Tempol and resolved by copper supplementation. • Global DNA hypomethylation was resolved both by Tempol and by copper supplementation. • Placental oxidative stress parameters coincides previous findings in the fetal liver.« less

Authors:
 [1];  [2]; ;  [1]; ;  [3];  [2];  [1]
  1. Hebrew University Hadassah Medical School, Jerusalem (Israel)
  2. Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada)
  3. Department of Obstetrics and Gynecology, University of Rochester, Rochester (United States)
Publication Date:
OSTI Identifier:
22439708
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 276; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANOXIA; APOPTOSIS; COPPER; COPPER SULFATES; DIET; DISEASE INCIDENCE; DNA; DRINKING WATER; FETUSES; GENES; GROWTH FACTORS; LIVER; METHYLATION; OXIDATION; PLACENTA; PREGNANCY; RATS; STRESSES; WEIGHT

Citation Formats

Ergaz, Zivanit, Guillemin, Claire, Neeman-azulay, Meytal, Weinstein-Fudim, Liza, Stodgell, Christopher J., Miller, Richard K., Szyf, Moshe, and Ornoy, Asher. Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat. United States: N. p., 2014. Web. doi:10.1016/J.TAAP.2014.02.017.
Ergaz, Zivanit, Guillemin, Claire, Neeman-azulay, Meytal, Weinstein-Fudim, Liza, Stodgell, Christopher J., Miller, Richard K., Szyf, Moshe, & Ornoy, Asher. Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat. United States. https://doi.org/10.1016/J.TAAP.2014.02.017
Ergaz, Zivanit, Guillemin, Claire, Neeman-azulay, Meytal, Weinstein-Fudim, Liza, Stodgell, Christopher J., Miller, Richard K., Szyf, Moshe, and Ornoy, Asher. 2014. "Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat". United States. https://doi.org/10.1016/J.TAAP.2014.02.017.
@article{osti_22439708,
title = {Placental oxidative stress and decreased global DNA methylation are corrected by copper in the Cohen diabetic rat},
author = {Ergaz, Zivanit and Guillemin, Claire and Neeman-azulay, Meytal and Weinstein-Fudim, Liza and Stodgell, Christopher J. and Miller, Richard K. and Szyf, Moshe and Ornoy, Asher},
abstractNote = {Fetal Growth Restriction (FGR) is a leading cause for long term morbidity. The Cohen diabetic sensitive rats (CDs), originating from Wistar, develop overt diabetes when fed high sucrose low copper diet (HSD) while the original outbred Sabra strain do not. HSD induced FGR and fetal oxidative stress, more prominent in the CDs, that was alleviated more effectively by copper than by the anti-oxidant vitamins C and E. Our aim was to evaluate the impact of copper or the anti-oxidant Tempol on placental size, protein content, oxidative stress, apoptosis and total DNA methylation. Animals were mated following one month of HSD or regular chow diet and supplemented throughout pregnancy with either 0, 1 or 2 ppm of copper sulfate or Tempol in their drinking water. Placental weight on the 21st day of pregnancy decreased in dams fed HSD and improved upon copper supplementation. Placental/fetal weight ratio increased among the CDs. Protein content decreased in Sabra but increased in CDs fed HSD. Oxidative stress biochemical markers improved upon copper supplementation; immunohistochemistry for oxidative stress markers was similar between strains and diets. Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. Placental global DNA methylation was decreased only among the CDs dams fed HSD. We conclude that FGR in this model is associated with smaller placentae, reduced DNA placental methylation, and increased oxidative stress that normalized with copper supplementation. DNA hypomethylation makes our model a unique method for investigating genes associated with growth, oxidative stress, hypoxia and copper. - Highlights: • Sensitive Cohen diabetic rats (CDs) had small placentae and growth restricted fetuses. • CDs dams fed high sucrose low copper diet had placental global DNA hypomethylation. • Caspase 3 was positive in more placentae of dams fed HSD than those fed RD. • Oxidative stress parameters improved by Tempol and resolved by copper supplementation. • Global DNA hypomethylation was resolved both by Tempol and by copper supplementation. • Placental oxidative stress parameters coincides previous findings in the fetal liver.},
doi = {10.1016/J.TAAP.2014.02.017},
url = {https://www.osti.gov/biblio/22439708}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 3,
volume = 276,
place = {United States},
year = {Thu May 01 00:00:00 EDT 2014},
month = {Thu May 01 00:00:00 EDT 2014}
}