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Restriction of placental function alters heart development in the sheep fetus
1 Center for the Early Origins of Adult Health, Discipline of Physiology, University of Adelaide, Adelaide, South Australia; 2 Early Origins of Adult Health Research Group, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia;...
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Published in: | American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2007-07, Vol.293 (1), p.R306-R313 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
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Online Access: | Get full text |
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Summary: | 1 Center for the Early Origins of Adult Health, Discipline of Physiology, University of Adelaide, Adelaide, South Australia; 2 Early Origins of Adult Health Research Group, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia; and 3 Heart Research Center, Oregon Health and Science University, Portland, Oregon
Submitted 13 November 2006
; accepted in final form 9 April 2007
Placental insufficiency, resulting in restriction of fetal substrate supply, is a major cause of intrauterine growth restriction (IUGR) and increased neonatal morbidity. Fetal adaptations to placental restriction maintain the growth of key organs, including the heart, but the impact of these adaptations on individual cardiomyocytes is unknown. Placental and hence fetal growth restriction was induced in fetal sheep by removing the majority of caruncles in the ewe before mating (placental restriction, PR). Vascular surgery was performed on 13 control and 11 PR fetuses at 110125 days of gestation (term: 150 ± 3 days). PR fetuses with a mean gestational P O 2 < 17 mmHg were defined as hypoxic. At postmortem (135 days), fetal hearts were collected, and cardiomyocytes were isolated and fixed. Proliferating cardiomyocytes were counted by immunohistochemistry of Ki67 protein. Cardiomyocytes were stained with methylene blue to visualize the nuclei, and the proportion of mononucleated cells and length and width of cardiomyocytes were measured. PR resulted in chronic fetal hypoxia, IUGR, and elevated plasma cortisol concentrations. Although there was no difference in relative heart weights between control and PR fetuses, there was an increase in the proportion of mononucleated cardiomyocytes in PR fetuses. Whereas mononucleated and binucleated cardiomyocytes were smaller, the relative size of cardiomyocytes when expressed relative to heart weight was larger in PR compared with control fetuses. The increase in the relative proportion of mononucleated cardiomyocytes and the relative sparing of the growth of individual cardiomyocytes in the growth-restricted fetus are adaptations that may have long-term consequences for heart development in postnatal life.
hypoxia; cardiomyocyte; fetal growth restriction; hyperplasia; hypertrophy; placental restriction
Address for reprint requests and other correspondence: J. Morrison, Sansom Institute, School of Pharmacy and Medical Sciences, City East Campus, Univ. of South Australia |
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ISSN: | 0363-6119 1522-1490 |
DOI: | 10.1152/ajpregu.00798.2006 |