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Effects of maternal iron restriction in the rat on hypoxia-induced gene expression and fetal metabolite levels

Published online by Cambridge University Press:  09 March 2007

Rohan M. Lewis ,
Lynwen A. James ,
Junlong Zhang ,
Christopher D. Byrne  and
C. Nicholas Hales
Rohan M. Lewis*
Affiliation:
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QR, UK
Lynwen A. James
Affiliation:
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QR, UK
Junlong Zhang
Affiliation:
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QR, UK
Christopher D. Byrne
Affiliation:
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QR, UK
C. Nicholas Hales
Affiliation:
Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge CB2 2QR, UK
*
Corresponding author: Dr Rohan M. Lewis, present address Department of Obstetrics and Gynaecology, University of Southampton, Princess Ann Hospital, Coxford Road, Southampton SO16 5YA, UK, fax +44 2380 786933 email: [email protected]
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Abstract

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The mechanism by which maternal Fe deficiency in the rat causes fetal growth retardation has not been clearly established. This study compared the effects on the fetuses from dams fed a control diet with two groups of dams fed Fe-restricted diets. One Fe-restricted group was fed the Fe-restricted diet for 1 week prior to mating and throughout gestation and the second Fe-restricted group was fed the Fe-restricted diet for 2 weeks prior to mating and throughout gestation. On day 21 of gestation Fe-restricted dams, and their fetuses, were anaemic. Fetal weight was reduced in both Fe-restricted groups compared with controls. Expression of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) are induced by hypoxia. The levels of HIF-1α mRNA were highest in placenta, then in kidney, heart and liver but were not different between the groups. Levels of plasma VEGF were not different between the groups. Maternal plasma triacylglycerol was decreased in the 1-week Fe-restricted dams compared with controls. Maternal plasma cholesterol and free fatty acid levels were not different between the groups. In fetal plasma, levels of triacylglycerol and cholesterol were decreased in both Fe-restricted groups. In maternal plasma, levels of a number of amino acids were elevated in both Fe-restricted groups. In contrast, levels of a number of amino acids in fetal plasma were lower in both Fe-restricted groups. Fetal plasma lactate was increased in Fe-restricted fetuses but fetal plasma glucose and β-hydroxybutyrate were not affected. These changes in fetal metabolism may contribute to fetal growth retardation in this model. This study does not support the hypothesis that the Fe-restricted fetus is hypoxic.

Keywords

Iron-deficiency anaemiaFetal growth retardationFetal nutrition
Type
Research Article
Information
British Journal of Nutrition , Volume 85 , Issue 2 , February 2001 , pp. 193 - 201
Copyright
Copyright © The Nutrition Society 2001

References

Bergeron, M, Yu, AY, Solway, KE, Semenza, GL & Sharp, FR (1999) Induction of hypoxia-inducible factor-1 (HIF-1) and its target genes following focal ischaemia in rat brain European Journal of Neuroscience 11, 4159–4170.CrossRefGoogle ScholarPubMed
Coleman, RA (1986) Placental metabolism and transport of lipid Federation Proceedings 45, 2519–2523.Google ScholarPubMed
Crowe, C, Dandekar, P, Fox, M, Dhingra, K, Bennet, L & Hanson, MA (1995) The effects of anaemia on heart, placenta and body weight, and blood pressure in fetal and neonatal rats Journal of Physiology 488, 515–519.CrossRefGoogle ScholarPubMed
Davis, LE & Hohimer, AR (1991) Hemodynamics and organ blood flow in fetal sheep subjected to chronic anemia American Journal of Physiology 261, R1542-R1548.Google ScholarPubMed
Doughty, IM, & Sibley, CP (1995) Placental Transfer. In Fetal and Neonatal Physiology & Clinical Applications, pp. 3–29. [Hanson, MA, Spencer, JAD, and Rodeck, CH, editors]. Cambridge: Cambridge University Press.Google Scholar
Felt, BT & Lozoff, B (1996) Brain iron and behavior of rats are not normalized by treatment of Fe-deficiency anemia during early development Journal of Nutrition 126, 693–701.CrossRefGoogle Scholar
Forsythe, JA, Jiang, BH, Iyer, NV, Agani, F, Leung, SW, Koos, RD & Semenza, GL (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1 Molecular and Cellular Biology 16, 4604–4613.CrossRefGoogle ScholarPubMed
Goldberg, MA & Schneider, TJ (1994) Similarities between the oxygen-sensing mechanisms regulating the expression of vascular endothelial growth factor and erythropoietin Journal of Biological Chemistry 269, 4355–4359.CrossRefGoogle ScholarPubMed
Hebbel, RP, Berger, EM & Eaton, JW (1980) Effect of increased maternal hemoglobin oxygen affinity on fetal growth in the rat Blood 55, 969–974.CrossRefGoogle ScholarPubMed
Jung, F, Palmer, LA, Zhou, N & Johns, RA (2000) Hypoxic regulation of inducible nitric oxide synthase via hypoxia inducible factor-1 in cardiac myocytes Circulation Reseach 86, 319–325.CrossRefGoogle ScholarPubMed
Law, CM & Shiell, AW (1996) Is blood pressure inversely related to birth weight? The strength of evidence from a systematic review of the literature Journal of Hypertension 14, 935–941.CrossRefGoogle ScholarPubMed
Lewis, RM, Bassett, NS, Johnston, BM & Skinner, SJ (1998) Fetal and placental glucose and amino acid uptake in the spontaneously hypertensive rat Placenta 19, 403–408.CrossRefGoogle ScholarPubMed
Lueder, FL, Kim, SB, Buroker, CA, Bangalore, SA & Ogata, ES (1995) Chronic maternal hypoxia retards fetal growth and increases glucose utilization of select fetal tissues in the rat Metabolism 44, 532–537.CrossRefGoogle ScholarPubMed
McCormick, MC (1985) The contribution of low birth weight to infant mortality and childhood morbidity New England Journal of Medicine 312, 82–90.CrossRefGoogle ScholarPubMed
Mackler, B, Grace, R, Person, R, Shepard, TH & Finch, CA (1983) Iron deficiency in the rat: biochemical studies of fetal metabolism Teratology 28, 103–107.CrossRefGoogle ScholarPubMed
Mackler, B, Person, R, Miller, LR & Finch, CA (1979) Iron deficiency in the rat: effects on phenylalanine metabolism Pediatric Research 13, 1010–1011.CrossRefGoogle ScholarPubMed
Martin, C, Yu, AY, Jiang, BH, Davis, L, Kimberly, D, Hohimer, AR & Semenza, GL (1998) Cardiac hypertrophy in chronically anemic fetal sheep: Increased vascularization is associated with increased myocardial expression of vascular endothelial growth factor and hypoxia-inducible factor 1 American Journal of Obstetrics and Gynecology 178, 527–534.CrossRefGoogle ScholarPubMed
Rosso, P (1977) Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of alpha-amino isobutyric acid Journal of Nutrition 107, 2002–2005.CrossRefGoogle ScholarPubMed
Semenza, GL, Agani, F, Booth, G, Forsythe, J, Iyer, N, Jiang, BH, Leung, S, Roe, R, Wiener, C & Yu, A (1997) Structural and functional analysis of hypoxia-inducible factor 1 Kidney International 51, 553–555.CrossRefGoogle ScholarPubMed
Shepard, TH, Mackler, B & Finch, CA (1980) Reproductive studies in the iron-deficient rat Teratology 22, 329–334.CrossRefGoogle ScholarPubMed
Singla, PN, Tyagi, M, Kumar, A, Dash, D & Shankar, R (1997) Fetal growth in maternal anaemia Journal of Tropical Pediatrics 43, 89–92.CrossRefGoogle ScholarPubMed
Sochor, M, Baquer, NZ & McLean, P (1982) Bio-inorganic regulation of pathways of carbohydrate and lipid metabolism. II. The effect of iron-deficiency on the profile of enzymes in the developing rat adrenal gland Enzyme 27, 149–155.CrossRefGoogle ScholarPubMed
Stangl, GI & Kirchgessner, M (1998) Different degrees of moderate iron deficiency modulate lipid metabolism of rats Lipids 33, 889–895.CrossRefGoogle ScholarPubMed
Stangl, GI & Kirchgessner, M (1998) Effect of different degrees of moderate iron deficiency on the activities of tricarboxylic acid cycle enzymes, and the cytochrome oxidase, and the iron, copper, and zinc concentrations in rat tissues Zeitschrift fur Ernahrungswiss 37, 260–268.CrossRefGoogle ScholarPubMed
Steer, P, Alam, MA, Wadsworth, J & Welch, A (1995) Relation between maternal haemoglobin concentration and birth weight in different ethnic groups British Medical Journal 310, 489–491.CrossRefGoogle ScholarPubMed
Stephenson, T, Stammers, J & Hull, D (1993) Placental transfer of free fatty acids: importance of fetal albumin concentration and acid-base status Biology of the Neonate 63, 273–280.CrossRefGoogle ScholarPubMed
van den Broek, N (1998) Anaemia in pregnancy in developing countries British Journal of Obstetrics and Gynaecology 105, 385–390.CrossRefGoogle ScholarPubMed
Van #Geijn, HP, Kaylor, WM, Nicola, KR & Zuspan, FP (1980) Induction of severe intrauterine growth retardation in the Sprague-Dawley rat American Journal of Obstetrics and Gynecology 137, 43–47.CrossRefGoogle ScholarPubMed
Van #Thiel, DH, Estes, LW, Richey, JE, Little, JM & Graham, TO (1980) Fetal rat hepatic ultrastructural changes associated with organ culture and glucocorticoid treatment Endocrinology 107, 557–565.CrossRefGoogle ScholarPubMed
Wiener, CM, Booth, G & Semenza, GL (1996) In vivo expression of mRNAs encoding hypoxia-inducible factor 1 Biochemical and Biophysical Research Communications 225, 485–488.CrossRefGoogle ScholarPubMed
Zhang, J & Byrne, CD (1997) A novel highly reproducible quantitative competitve RT PCR system Journal of Molecular Biology 274, 338–352.CrossRefGoogle ScholarPubMed
Zhou, LM, Yang, WW, Hua, JZ, Deng, CQ, Tao, X & Stoltzfus, RJ (1998) Relation of hemoglobin measured at different times in pregnancy to preterm birth and low birth weight in Shanghai, China American Journal of Epidemiology 148, 998–1006.CrossRefGoogle ScholarPubMed