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

• Published in: Toxicology and applied pharmacology Vol. 265; no. 2; pp. 209 - 220
• Main Authors: Ergaz, Zivanit, Shoshani-Dror, Dana, Guillemin, Claire, Neeman-azulay, Meytal, Fudim, Liza, Weksler-Zangen, Sarah, Stodgell, Christopher J., Miller, Richard K., Ornoy, Asher
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.12.2012; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; ANOXIA; ANTIOXIDANTS; Biological and medical sciences; BLOOD; CATALASE; Catalase - metabolism; Chemical and industrial products toxicology. Toxic occupational diseases; COPPER; Copper - administration & dosage; Copper - blood; Copper - deficiency; Copper - metabolism; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; DIET; DRINKING WATER; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Female; Fetal growth restriction; Fetal Growth Retardation - genetics; Fetal Growth Retardation - metabolism; Fetal resorption; Fetus; FETUSES; HYPERGLYCEMIA; Hypoxia; Immunohistochemistry; Inbreeding; Linear Models; Litter Size; LIVER; Liver - enzymology; Liver - metabolism; Malondialdehyde; Malondialdehyde - metabolism; Medical sciences; Metals and various inorganic compounds; nitrotyrosine; Nutrient deficiency; OXIDATION; Oxidative stress; Oxidative Stress - genetics; Oxidative Stress - physiology; OXIDIZERS; Placenta; PREGNANCY; RATS; Rats, Wistar; SACCHAROSE; Sucrose; SUPEROXIDE DISMUTASE; Superoxide Dismutase - metabolism; Toxicology; FGR; CDr; Oxidative stress; RD; CDs; Fetal growth restriction; HSD; Rats; Fetal resorption; Copper deficiency; Diabetes; PGD; Endocrinopathy; Animal model; Rat; Digestive system; Diabetes mellitus; Deficiency; Liver; Rodentia; Transition metal; Antioxidant; Growth retardation; Vertebrata; Fetal development; Mammalia; Animal; Copper
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2012.10.006

High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1ppm or 2ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1ppm and 2ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and oxidative stress of liver