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The expression of growth-arrest genes in the liver and kidney of the protein-restricted rat fetus

Published online by Cambridge University Press:  08 March 2007

Christopher A. Maloney ,
Christina Lilley ,
Morven Cruickshank ,
Caroline McKinnon ,
Susan M. Hay  and
William D. Rees
Christopher A. Maloney
Affiliation:
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Christina Lilley
Affiliation:
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Morven Cruickshank
Affiliation:
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Caroline McKinnon
Affiliation:
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
Susan M. Hay
Affiliation:
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
William D. Rees*
Affiliation:
The Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, UK
*
*Corresponding author: Dr William D. Rees, fax +44 (0) 1224 715349, email [email protected]
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Abstract

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During fetal life, there are periods of rapid cell proliferation, which are uniquely sensitive to nutritional perturbation. Feeding the pregnant rat a protein-restricted diet alters the growth trajectory of major fetal organs such as the kidney. By day 21 of gestation, the ratio of kidney weight to total body weight is reduced in the fetuses of dams fed a protein-deficient diet. In contrast, the ratio of fetal liver weight to total body weight is unchanged. To investigate the mechanisms underlying this disproportionate change in organ growth in the low-protein group, cell proliferation and differentiation have been assessed in the liver and kidney. The steady-state levels of mRNA for the growth-arrest and DNA-damage gene gadd153/CHOP-10, CCAAT enhancer-binding proteins α and β were unaffected by maternal diet in both fetal liver and kidney. The mRNA for alpha-fetoprotein, albumin and hepatic glucokinase were unchanged in the liver, suggesting that maternal protein deficiency does not alter the state of differentiation. The steady-state levels of the mRNA coding for the cyclin-dependent protein kinase inhibitors (p15INK4a, p19INK4d, p21CIP1, p27KIP1 and p57KIP2) were unchanged in the fetal livers but were significantly increased in the kidneys of fetuses from dams fed the low-protein diet. These results show that the asymmetrical growth of the kidney is associated with increases in mRNA for the Cip/Kip cyclin-dependent kinase inhibitors and that these may reflect specific lesions in organ development.

Keywords

Fetal programmingLow-protein dietFetal origins of adult diseaseCell cycleOrgan development
Type
Research Article
Information
British Journal of Nutrition , Volume 94 , Issue 1 , July 2005 , pp. 12 - 18
Copyright
Copyright © The Nutrition Society 2005

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