Hostname: page-component-586b7cd67f-2plfb Total loading time: 0 Render date: 2024-11-26T15:15:52.888Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of maternal iron restriction during pregnancy on renal morphology in the adult rat offspring

Published online by Cambridge University Press:  07 June 2007

S. J. M. Lisle ,
R. M. Lewis ,
C. J. Petry ,
S. E. Ozanne ,
C. N. Hales  and
A. J. Forhead
S. J. M. Lisle
Affiliation:
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
R. M. Lewis
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Adenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, UK
C. J. Petry
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Adenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, UK
S. E. Ozanne
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Adenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, UK
C. N. Hales
Affiliation:
Department of Clinical Biochemistry, University of Cambridge, Adenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, UK
A. J. Forhead*
Affiliation:
Department of Physiology, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
*
*Corresponding author: Dr Alison J. Forhead, fax +44 1223 333840, email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

In rats, maternal anaemia during pregnancy causes hypertension in the adult offspring, although the mechanism is unknown. The present study investigated the renal morphology of adult rats born to mothers who were Fe-deficient during pregnancy. Rats were fed either a control (153 mg Fe/kg diet, n 7) or low-Fe (3 mg/kg diet, n 6) diet from 1 week before mating and throughout gestation. At delivery, the Fe-restricted (IR) mothers were anaemic; the IR pups were also anaemic and growth-retarded at 2 d of age. At 3 and 16 months, systolic blood pressure in the IR offspring (163 (sem 4) and 151 (sem 4) mmHg respectively, n 13) was greater than in control animals (145 (sem 3) and 119 (sem 4) mmHg respectively, n 15, P<0·05). At post mortem at 18 months, there was no difference in kidney weight between treatment groups, although relative kidney weight as a fraction of body weight in the IR offspring was greater than in control animals (P<0·05). Glomerular number was lower in the IR offspring (11·4 (sem 1·1) per 4mm2, n 13) compared with control rats (14·8 (sem 0·7), n 15, P<0·05). Maternal treatment had no effect on glomerular size, but overall, female rats had smaller and more numerous glomeruli per unit area than male rats. When all animals were considered, inverse relationships were observed between glomerular number and glomerular size (r−0·73, n 28, P<0·05), and glomerular number and systolic blood pressure at both 3 months (r−0·42, n 28, P<0·05) and 16 months of age (r−0·64, n 28, P<0·05). Therefore, in rats, maternal Fe restriction causes hypertension in the adult offspring that may be due, in part, to a deficit in nephron number.

Keywords

KidneyProgrammingFetus
Type
Research Article
Information
British Journal of Nutrition , Volume 90 , Issue 1 , July 2003 , pp. 33 - 39
Copyright
Copyright © The Nutrition Society 2003

References

Bains, RK, Sibbons, PD, Murray, RD, Howard, CV & Van Velzen, D (1996) Stereological estimation of the absolute number of glomeruli in the kidneys of lambs. Res Vet Sci 60, 122–125.CrossRefGoogle ScholarPubMed
Barone, A, Harper, RG & Wapnir, RA (1998) Placental copper transport in the rat. III: Interaction between copper and iron in maternal protein deficiency. Placenta 19, 113–118.CrossRefGoogle ScholarPubMed
Bassan, H, Trejo, LL, Kariv, N, et al. (2000) Experimental intrauterine growth retardation alters renal development. Pediatr Nephrol 15, 192–195.CrossRefGoogle ScholarPubMed
Bertram, C, Trowern, AR, Copin, N, Jackson, AA & Whorwood, CB (2001) The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11β-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142, 2841–2853.CrossRefGoogle ScholarPubMed
Brenner, BM, Garcia, DL & Anderson, S (1988) Glomeruli and blood pressure. Less of one, more of the other?. Am J Hypertens 1, 335–347.CrossRefGoogle Scholar
Campos, MS, Barrionuevo, M, Alferez, MJM, et al. (1998) Interactions among iron, calcium, phosphorus and magnesium in the nutritionally iron-deficient rat. Exp Physiol 83, 771–781.CrossRefGoogle ScholarPubMed
Celsi, G, Kistner, A, Aizman, R, et al. (1998) Prenatal dexamethasone causes oligonephronia, sodium retention, and higher blood pressure in the offspring. Pediatr Res 44, 317–322.CrossRefGoogle 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. J Physiol 488, 515–519.CrossRefGoogle ScholarPubMed
Doublier, S, Amri, K, Seurin, D, et al. (2001) Overexpression of human insulin-like growth factor binding protein-I in the mouse leads to nephron deficit. Pediatr Res 49, 660–666.CrossRefGoogle Scholar
Finch, CA, Huebers, HA, Miller, LR, Josephson, BM, Shepard, TH & Mackler, B (1983) Fetal iron balance in the rat. Am J Clin Nutr 37, 910–917.CrossRefGoogle ScholarPubMed
Gambling, L, Danzeisen, R, Gair, S et al. (2001 a) Effect of iron deficiency on placental transfer of iron and expression of iron transport proteins in vivo and in vitro. Biochem J 356, 883–889.CrossRefGoogle ScholarPubMed
Gambling, L, Dunford, S, Beattie, L & Mcardle, HJ (2001 b) Postnatal effects of prenatal iron deficiency in the rat. J Physiol 539, 118P, (Abstr).Google Scholar
Hinchliffe, SA, Lynch, MRJ, Sargent, PH, Howard, CV & Van Velzen, D (1992) The effect of intrauterine growth retardation on the development of renal nephrons. Br J Obstetr Gynaecol 99, 296–301.CrossRefGoogle ScholarPubMed
Hoet, JJ & Hanson, MA (1999) Intrauterine nutrition: its importance during critical periods for cardiovascular and endocrine development. J Physiol 514, 617–627.CrossRefGoogle ScholarPubMed
Horster, MF, Braun, GS & Huber, SM (1999) Embryonic renal epithelia: induction, nephrogenesis, and cell differentiation. Physiol Rev 79, 1157–1191.CrossRefGoogle ScholarPubMed
Jang, J-T, Green, JB, Beard, JL & Green, MH (2000) Kinetic analysis shows that iron deficiency decreases liver vitamin A mobilization in rats. J Nutr 130, 1291–1296.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJM & Jackson, AA (1999) Fetal exposure to a maternal low protein diet impairs nephrogenesis and promotes hypertension in the rat. Life Sci 64, 965–974.CrossRefGoogle ScholarPubMed
Lelievre-Pegorier, M, Vilar, J, Ferrier, M-L, et al. (1998 a) Mild vitamin A deficiency leads to inborn nephron deficit in the rat. Kidney Int 54, 1455–1462.CrossRefGoogle ScholarPubMed
Lelievre-Pegorier, M, Vilar, J, Freund, N, Gilbert, T & Merlet-Benichou, C (1998 b) Vitamin A prevents nephron deficit in growth-retarded fetal rats. J Am Soc Nephrol 9, 501 Abstr.Google Scholar
Lewis, RM, James, LA, Zhang, J, Byrne, CD & Hales, CN (2001 a) Effects of maternal iron restriction in the rat on hypoxia-induced gene expression and fetal metabolite levels. Br J Nutr 85, 193–201.CrossRefGoogle ScholarPubMed
Lewis, RM, Petry, CJ, Ozanne, SE, & Hales, CN (2001 b) Effects of maternal iron restriction in the rat on blood pressure, glucose tolerance, and serum lipids in the 3-month-old offspring. Metabolism 50, 562–567.CrossRefGoogle ScholarPubMed
Lucas, SRR, Miraglia, SM, Gil, FZ & Coimbra, TM (2001) Intrauterine food restriction as a determinant of nephrosclerosis. American Journal of Kidney Diseases 37, 467–476.CrossRefGoogle Scholar
Manalich, R, Reyes, L, Herrera, M, Melendi, C & Fundora, I (2000) Relationship between weight at birth and the number and size of renal glomeruli in humans: a histomorphometric study. Kidney Int 58, 770–773.CrossRefGoogle ScholarPubMed
Merlet-Benichou, C, Gilbert, T, Muffat-Joly, M & Lelievre-Pegorier, M (1994) Intrauterine growth retardation leads to a permanent nephron deficit in the rat. Pediatr Nephrol 8, 175–180.CrossRefGoogle ScholarPubMed
Messow, C, Gartner, K, Hackbarth, H, Kangaloo, M & Lunebrink, L (1980) Sex differences in kidney morphology and glomerular filtration rate in mice. Pediatr Nephrol 19, 51–55.Google ScholarPubMed
Mosier, HD, Spencer, EM, Dearden, LC & Jansons, RA (1987) The effect of glucocorticoids on plasma insulin-like growth factor I concentration in the rat fetus. Pediatr Res 22, 92–95.CrossRefGoogle ScholarPubMed
Rogers, SA, Ryan, G & Hammerman, MR (1991) Insulin-like growth factors I and II are produced in the metanephros and are required for growth and development in vitro. J Cell Biol 113, 1447–1453.CrossRefGoogle ScholarPubMed
Rondo, PHC, Abbott, R, Rodrigues, LC & Tomkins, AM (1995) Vitamin A, folate, and iron concentrations in cord and maternal blood of intra-uterine growth retarded and appropriate birth weight babies. Eur J Clin Nutr 49, 391–399.Google ScholarPubMed
Singla, PN, Tyagi, M, Shankar, R, Dash, D & Kumar, A (1996) Fetal iron status in maternal anemia. Acta Pediatr 85, 1327–1330.CrossRefGoogle ScholarPubMed
Tapanainen, PJ, Bang, P, Wilson, K, Unterman, TG, Vreman, HJ & Rosenfeld, RG (1994) Maternal hypoxia as a model for intrauterine growth retardation: effects on insulin-like growth factors and their binding proteins. Pediatr Res 36, 152–158.CrossRefGoogle Scholar
Tufro-Mcreddie, A, Norwood, VF, Aylor, KW, Botkin, SJ, Carey, RM & Gomez, RA (1997) Oxygen regulates vascular endothelial growth factor-mediated vasculogenesis and tubulogenesis. Dev Biol 183, 139–149.CrossRefGoogle ScholarPubMed
Vaquero, MP & Navarro, MP (1996) Relationship between moderate food restriction during pregnancy and Fe, Zn and Cu contents in maternal tissues and foetuses. Reprod Nutr Dev 36, 333–344.CrossRefGoogle ScholarPubMed
Vehaskari, VM, Aviles, DH & Manning, J (2001) Prenatal programming of adult hypertension in the rat. Kidney Int 59, 238–245.CrossRefGoogle ScholarPubMed
Wintour, EM (1997) The renin-angiotensin system and the development of the kidney. Trends Endocrinol Metab 8, 199–207.Google Scholar