TY - JOUR
T1 - The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model
AU - Ergaz, Zivanit
AU - Shoshani-Dror, Dana
AU - Guillemin, Claire
AU - Neeman-azulay, Meytal
AU - Fudim, Liza
AU - Weksler-Zangen, Sarah
AU - Stodgell, Christopher J.
AU - Miller, Richard K.
AU - Ornoy, Asher
PY - 2012/12/1
Y1 - 2012/12/1
N2 - 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 1. ppm or 2. ppm 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 1. ppm and 2. ppm 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.
AB - 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 1. ppm or 2. ppm 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 1. ppm and 2. ppm 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.
KW - CDr
KW - CDs
KW - Copper deficiency
KW - Diabetes
KW - Fetal growth restriction
KW - Fetal resorption
KW - FGR
KW - HSD
KW - Oxidative stress
KW - PGD
KW - Rats
KW - RD
UR - http://www.scopus.com/inward/record.url?scp=84868459947&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2012.10.006
DO - 10.1016/j.taap.2012.10.006
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C2 - 23079581
AN - SCOPUS:84868459947
SN - 0041-008X
VL - 265
SP - 209
EP - 220
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 2
ER -