Hostname: page-component-cd9895bd7-gxg78 Total loading time: 0 Render date: 2024-12-24T16:22:10.007Z Has data issue: false hasContentIssue false
  • English
  • Français

Maternal protein restriction and fetal growth: lack of evidence of a role for homocysteine in fetal programming

Published online by Cambridge University Press:  08 March 2007

Simon C. Langley-Evans ,
Christina Lilley  and
Sarah McMullen
Simon C. Langley-Evans*
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK
Christina Lilley
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK
Sarah McMullen
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK
*
*Corresponding author: Dr Simon C. Langley-Evans, fax +44 (0)115 951 6122, 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.

The disease-programming effects of a maternal low-protein (MLP) diet in rat pregnancy have been suggested to be attributable of hyperhomocysteinaemia. The aim of the present study was to determine whether MLP feeding impacted upon maternal and day 20 fetal homocysteine concentrations, with ensuing effects upon oxidan/ntioxidant status. Sixty-four pregnant rats were fed either MLP diet or control diet before termination of pregnancy at days 4, 10, 18 or 20 gestation (full-term gestation 22d). Maternal plasma homocysteine concentrations were similar in control and MLP-fed dams at all points in gestation. Fetal plasma homocysteine was similarly unaffected by MLP feeding at day 20 gestation. Activities of superoxide dismutase and glutathione peroxidase were similar in livers of mothers and fetuses in the two groups. Whilst catalase activity was not influenced by diet in maternal liver, MLP exposure increased catalase activity in fetal liver at day 20. Oxidative injury (protein carbonyl concentration) was lower in the livers of MLP-fed animals at day 18 gestation (P<0·05), but significantly greater at day 20. Hepatic expression of methionine synthase was similar in control and MLP-fed dams at all stages of gestation. Expression of DNA methyltransferase 1 in fetal liver was altered by maternal diet in a sex- and gestational age-specific manner. In conclusion, MLP feeding does not impact upon maternal or fetal homocysteine concentrations prior to day 20 gestation in the rat. There was no evidence of increased oxidative injury in fetal tissue that might explain the long-term programming effects of the diet.

Keywords

ProgrammingPregnancyHomocysteineAntioxidants
Type
Research Article
Information
British Journal of Nutrition , Volume 96 , Issue 3 , September 2006 , pp. 578 - 586
Copyright
Copyright © The Nutrition Society 2006

References

Aebi, H (1984) Catalase in vitro. Methods Enzymol 105, 114–121.Google ScholarPubMed
Bogdarina, I, Murphy, HC, Burns, SP & Clark, AJ (2004) Investigation of the role of epigenetic modification of the rat glucokinase gene in fetal programming. Life Sci 74, 1407–1415.CrossRefGoogle ScholarPubMed
Bradford, MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248–254.CrossRefGoogle ScholarPubMed
Brawley, L, Torrens, C, Anthony, FW, Itoh, S, Wheeler, T, Jackson, AA, Clough, GF, Poston, L & Hanson, MA (2004) Glycine rectifies vascular dysfunction induced by dietary protein imbalance during pregnancy. J Physiol 554, 497–504.CrossRefGoogle ScholarPubMed
Chiang, PK (1998) Biological effects of inhibitors of S-adenosylhomocysteine hydrolase. Pharmacol Ther 77, 115–134.CrossRefGoogle ScholarPubMed
Gambling, L, Dunford, S, Wallace, DI, Zuur, G, Solanky, N, Srai, SK & McArdle, H (2003) Iron deficiency during pregnancy affects postnatal blood pressure in the rat. J Physiol 552, 603–610.CrossRefGoogle ScholarPubMed
Gluckman, PD & Hanson, MA (2004) Living with the past: evolution, development, and patterns of disease. Science 305, 1733–1736.CrossRefGoogle ScholarPubMed
Huang, CJ & Fwu, ML (1992) Protein insufficiency aggravates the enhanced lipid peroxidation and reduced activities of antioxidative enzymes in rats fed diets high in polyunsaturated fat. J Nutr 122, 1182–1189.CrossRefGoogle ScholarPubMed
Jackson, AA, Dunn, RL, Marchand, MC & Langley-Evans, SC (2003) Increased systolic blood pressure in rats induced by maternal low protein diet is reversed by dietary supplementation with glycine. Clin Sci 103, 633–639.CrossRefGoogle Scholar
Khan, IY, Taylor, PD, Dekou, V, Seed, PT, Lakasing, L, Graham, D, Dominiczak, AF, Hanson, MA & Poston, L (2003) Gender-linked hypertension in offspring of lard-fed pregnant rats. Hypertension 41, 168–175.CrossRefGoogle ScholarPubMed
Langley, SC, Browne, RF & Jackson, AA (1994) Altered glucose tolerance in rats exposed to maternal low protein diets in utero. Comp Biochem Physiol 109, 223–229.CrossRefGoogle ScholarPubMed
Langley, SC & Jackson, AA (1994) Increased systolic blood pressure in adult rats, induced by fetal exposure to maternal low protein diets. Clin Sci 86, 217–222.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (2001) Fetal programming of cardiovascular function through exposure to maternal undernutrition. Proc Nutr Soc 60, 505–513.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Gardner, DS & Jackson, AA (1996a) Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. J Reprod Fertil 106, 307–312.CrossRefGoogle ScholarPubMed
Langley-Evans, SC & Nwagwu, M (1998) Impaired growth and increased glucocorticoid-sensitive enzyme activities in tissues of rat fetuses exposed to maternal low protein diets. Life Sci 63, 605–615.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Phillips, GJ & Jackson, AA (1994) In utero exposure to maternal low protein diets induces hypertension in weanling rats, independently of maternal blood pressure changes. Clin Nutr 13, 319–324.CrossRefGoogle ScholarPubMed
Langley-Evans, SC & Sculley, DV (2005) Programming of hepatic antioxidant capacity and oxidative injury in the ageing rat. Mech Ageing Dev 126, 804–812.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
Langley-Evans, SC, Welham, SJM, Sherman, RC & Jackson, AA (1996b) Weanling rats exposed to maternal low protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clin Sci 91, 607–615.CrossRefGoogle ScholarPubMed
Levine, RL, Garland, D, Oliver, CN, Amici, A, Climent, I, Lenz, AG, Ahn, BW, Shaltiel, S & Stadmann, EM (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186, 464–478.CrossRefGoogle ScholarPubMed
Li, E, Bestor, TH & Jaenisch, R (1992) Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 69, 915–926.CrossRefGoogle ScholarPubMed
Lillycrop, KA, Phillips, ES, Jackson, AA, Hanson, MA & Burdge, GC (2005) Dietary protein restriction of pregnant rats induces and folic acid supplementation prevents epigenetic modification of hepatic gene expression in the offspring. J Nutr 135, 382–386.CrossRefGoogle ScholarPubMed
McMillen, IC & Robinson, JS (2005) Developmental origins of the metabolic syndrome: prediction, plasticity, and programming. Physiol Rev 85, 571–633.CrossRefGoogle ScholarPubMed
McMullen, S & Langley-Evans, SC (2005) Sex-specific effects of prenatal low-protein and carbenoxolone exposure on renal angiotensin receptor expression in rats. Hypertension 46, 1374–1380.CrossRefGoogle ScholarPubMed
Newell-Price, J, Clark, AJ & King, P (2000) DNA methylation and silencing of gene expression. Trends Endocrinol Metab 11, 142–148.CrossRefGoogle ScholarPubMed
Petrie, L, Duthie, SJ, Rees, WD & McConnell, JM (2002) Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming. Br J Nutr 88, 471–477.CrossRefGoogle ScholarPubMed
Rees, WD (2002) Manipulating the sulfur amino acid content of the early diet and its implications for long-term health. Proc Nutr Soc 61, 71–77.CrossRefGoogle ScholarPubMed
Rees, WD & Hay, SM (2001) Early changes in maternal sulphur amino acid metabolism caused by maternal protein deficiency. Pediatr Res 50, Suppl., 29A.Google Scholar
Saito, K, Sakai, N, Kim, HS, Ishizuka, M, Kazusaka, A & Fujita, S (2004) Strain differences in diazepam metabolism at its three metabolic sites in Sprague-Dawley, Brown Norway, Dark Agouti, and Wistar strain rats. Drug Metab Dispos 32, 959–965.Google ScholarPubMed
Sayer, AA, Dunn, RL, Langley-Evans, SC & Cooper, C (2001) Prenatal exposure to a maternal low protein diet shortens life span in rats. Gerontology 47, 9–14.CrossRefGoogle Scholar
Waterland, RA & Jirtle, RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23, 5293–5300.CrossRefGoogle ScholarPubMed
Winterbourn, C, Hawkins, R, Brian, M & Carrell, R (1975) The estimation of red cell superoxide dismutase activity. J Lab Clin Med 85, 337.Google ScholarPubMed
Young, L, Rees, WD & Sinclair, KD (2004) Programming in the preimplantation embryo. In Programming of Chronic Disease Through Fetal Exposure to Undernutrition, pp. 333–352 [Langley-Evans, SC, editor]. Wallingford: CABI Publishing.CrossRefGoogle Scholar