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Effects of hypoxia-induced intrauterine growth restriction on cardiac siderosis and oxidative stress

Published online by Cambridge University Press:  04 April 2012

C. F. Rueda-Clausen
Affiliation:
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Women and Children's Health Research Institute (WCHRI), University of Alberta, Edmonton, Alberta, Canada Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
J. S. Morton
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada Women and Children's Health Research Institute (WCHRI), University of Alberta, Edmonton, Alberta, Canada Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
G. Y. Oudit
Affiliation:
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada Department of Medicine, University of Alberta, Edmonton, Alberta, Canada Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
Z. Kassiri
Affiliation:
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada Women and Children's Health Research Institute (WCHRI), University of Alberta, Edmonton, Alberta, Canada Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
Y. Jiang
Affiliation:
Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada
S. T. Davidge
Affiliation:
Department of Physiology, University of Alberta, Edmonton, Alberta, Canada Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Alberta, Canada Women and Children's Health Research Institute (WCHRI), University of Alberta, Edmonton, Alberta, Canada Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada
Corresponding

Abstract

We have previously shown that adult rat offspring born intrauterine growth restricted (IUGR) as a result of a prenatal hypoxic insult exhibit several cardiovascular characteristics that are compatible with common manifestations of chronic iron toxicity. As hypoxia is one of the major regulators of iron absorption and metabolism, we hypothesized that hypoxia-induced IUGR offspring will have long-term changes in their ability to regulate iron metabolism leading to myocardial iron deposition and induction of myocardial oxidative stress. Pregnant Sprague Dawley rats were randomized to control (n = 8) or maternal hypoxia (11.5% oxygen; n = 8) during the last 6 days of pregnancy. At birth, litters were reduced to eight pups (four male and four female). At 4 or 12 months of age, offspring were euthanatized and samples (blood and myocardium) were collected. In only the male offspring, IUGR and aging were associated with an increase in myocardial markers of oxidative stress such as oxidized/reduced glutathione ratio and malondialdehyde. Aged male IUGR offspring also exhibited interstitial myocardial remodeling characterized by myocyte loss and disrupted extracellular matrix.Contrary to our hypothesis, however, neither IUGR nor aging were associated with changes in any systemic or local markers of iron metabolism. Our results suggest that hypoxic insults leading to IUGR produce long-term effects on the levels of oxidative stress and connective tissue distribution in the myocardium of male but not female offspring.

Type
Original Article
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2012

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