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Developmental programming of health and disease

Published online by Cambridge University Press:  07 March 2007

Simon C. Langley-Evans*
Affiliation:
School of Biosciences, University of Nottingham, Sutton Bonington, Loughborough LE12 5RD, UK
*
*Corresponding author: S Dr Simon Langley-Evans, fax +44 115 951 6122, email [email protected]
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Abstract

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The environment encountered in fetal and neonatal life exerts a profound influence on physiological function and risk of disease in adult life. Epidemiological evidence suggests that impaired fetal growth followed by rapid catch-up in infancy is a strong predictor of obesity, hypertension, non-insulin-dependent diabetes and CHD. Whilst these associations have been widely accepted to be the product of nutritional factors operating in pregnancy, evidence from human populations to support this assertion is scarce. Animal studies clearly demonstrate that there is a direct association between nutrient imbalance in fetal life and later disease states, including hypertension, diabetes, obesity and renal disease. These associations are independent of changes in fetal growth rates. Experimental studies examining the impact of micro- or macronutrient restriction and excess in rodent pregnancy provide clues to the mechanisms that link fetal nutrition to permanent physiological changes that promote disease. Exposure to glucocorticoids in early life appears to be an important consequence of nutrient imbalance and may lead to alterations in gene expression that have major effects on tissue development and function. Epigenetic mechanisms, including DNA methylation, may also be important processes in early-life programming.

Type
Nutrition Society Medal Lecture
Copyright
Copyright © The Nutrition Society 2006

References

Barker, DJ (2004) The developmental origins of chronic adult disease. Acta Paediatrica 93 Suppl. 2633CrossRefGoogle ScholarPubMed
Barker, DJ, Bull, AR, Osmond, C & Simmonds, SJ (1990) Fetal and placental size and risk of hypertension in adult life. British Medical Journal 301 259262.CrossRefGoogle ScholarPubMed
Barker, DJ, Hales, CN, Fall, CH, Osmond, C, Phipps, K & Clark, PM (1993 a) Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 36 6267.CrossRefGoogle ScholarPubMed
Barker, DJ & Osmond, C (1986) Infant mortality, childhood nutrition, and ischaemic heart disease in England and Wales. Lancet i 10771081.CrossRefGoogle Scholar
Barker, DJ, Osmond, C, Simmonds, SJ & Wield, GA (1993 b) The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life. British Medical Journal 306 422426.CrossRefGoogle ScholarPubMed
Barker, DJ, Winter, PD, Osmond, C, Margetts, B & Simmonds, SJ (1989) Weight in infancy and death from ischaemic heart disease. Lancet ii 577580.CrossRefGoogle Scholar
Beach, RS, Gershwin, ME & Hurley, LS (1982) Gestational zinc deprivation in mice: persistence of immunodeficiency for three generations. Science 218 469471.CrossRefGoogle ScholarPubMed
Bellinger, L, Lilley, CL, Langley-Evans, SC (2004) Prenatal exposure to a maternal low-protein diet programmes a preference for high-fat foods in the young adult rat. British Journal of Nutrition 92 513520.CrossRefGoogle ScholarPubMed
Benediktsson, R, Lindsay, RS, Noble, J, Seckl, JR & Edwards, CR (1993) Glucocorticoid exposure in utero: new model for adult hypertension. Lancet 341 339341.CrossRefGoogle ScholarPubMed
Bergel, E & Belizan, JM (2002) A deficient maternal calcium intake during pregnancy increases blood pressure of the offspring in adult rats. British Journal of Obstetrics and Gynaecology 109 540545.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 11beta-hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero. Endocrinology 142 28412853.CrossRefGoogle ScholarPubMed
Campbell, DM, Hall, MH, Barker, DJ, Cross, J, Shiell, AW & Godfrey, KM (1996) Diet in pregnancy and the offspring's blood pressure 40 years later. British Journal of Obstetrics and Gynaecology 103 273280.CrossRefGoogle ScholarPubMed
Daenzer, M, Ortmann, S, Klaus, S & Metges, CC (2002) Prenatal high protein exposure decreases energy expenditure and increases adiposity in young rats. Journal of Nutrition 132 142144.CrossRefGoogle ScholarPubMed
Dahri, S, Snoeck, A, Reusens-Billen, B, Remacle, C & Hoet, JJ (1990) Islet function in offspring of mothers on low protein diet during gestation. Diabetes 40 115120.CrossRefGoogle Scholar
Dodic, M, Abouantoun, T, O'Connor, A, Wintour, EM & Moritz, KM (2002) Programming effects of short prenatal exposure to dexamethasone in sheep. Hypertension 40 729734.CrossRefGoogle ScholarPubMed
Edwards, CR, Benediktsson, R, Lindsay, RS & Seckl, JR (1993) Dysfunction of placental glucocorticoid barrier: link between fetal environment and adult hypertension? Lancet 341 355357.CrossRefGoogle ScholarPubMed
Elmes, MJ, Gardner, DS, Langley-Evans, SC (2005) Prenatally programmed hypertension and its effects on the left ventricular pressure (LVP) function of the rat heart following ischemia reperfusion. Proceedings of the Nutrition Society 64 82A.Google Scholar
Eriksson, J, Forsen, T, Osmond, C & Barker, D (2003 a) Obesity from cradle to grave. International Journal of Obesity 27 722727.CrossRefGoogle ScholarPubMed
Eriksson, JG, Forsen, T, Tuomilehto, J, Osmond, C & Barker, DJ (2003 b) Early adiposity rebound in childhood and risk of Type 2 diabetes in adult life. Diabetologia 46 190194.CrossRefGoogle ScholarPubMed
Fall, CH, Osmond, C, Barker, DJ, Clark, PM, Hales, CN, Stirling, Y & Meade, TW (1995) Fetal and infant growth and cardiovascular risk factors in women. British Medical Journal 310 428432.CrossRefGoogle ScholarPubMed
Fazio, S & Linton, MF (2001) Mouse models of hyperlipidemia and atherosclerosis. Frontiers in Biosciences 6 D515D525.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. Journal of Physiology 552 603610.CrossRefGoogle ScholarPubMed
Gluckman, PD & Hanson, MA (2004) The developmental origins of the metabolic syndrome. Trends in Endocrinology and Metabolism 15 183187.CrossRefGoogle ScholarPubMed
Godfrey, KM (1998) Maternal regulation of fetal development and health in adult life. European Journal of Obstetrics Gynecology and Reproductive Biology 78 141150.CrossRefGoogle ScholarPubMed
Godfrey, KM (2002) The role of the placenta in fetal programming – a review. Placenta 23 Suppl. A S20S27.CrossRefGoogle ScholarPubMed
Godfrey, KM, Forrester, T, Barker, DJ, Jackson, AA, Landman, JP, Hall, JS, Cox, V & Osmond, C (1994) Maternal nutritional status in pregnancy and blood pressure in childhood. British Journal of Obstetrics and Gynaecology 101 398403.CrossRefGoogle ScholarPubMed
Gopalakrishnan, GS, Gardner, DS, Rhind, SM, Rae, MT, Kyle, CE, Brooks, AN, Walker, RM, Ramsay, MM, Keisler, DH, Stephenson, T & Symonds, ME (2004) Programming of adult cardiovascular function after early maternal undernutrition in sheep. American Journal of Physiology 287 R12R20.Google ScholarPubMed
Groot, PH, van Vlijmen, BJ, Benson, GM, Hofker, MH, Schiffelers, R, Vidgeon-Hart, M & Havekes, LM (1996) Quantitative assessment of aortic atherosclerosis in APOE*3 Leiden transgenic mice and its relationship to serum cholesterol exposure. Arteriosclerosis, Thrombosis, and Vascular Biology 16 926933.CrossRefGoogle ScholarPubMed
Hales, CN & Barker, DJP (2001) The thrifty phenotype hypothesis. British Medical Bulletin 60 520.CrossRefGoogle ScholarPubMed
Hales, CN, Barker, DJP, Clark, PMS, Cox, LJ, Fall, C, Osmond, C & Winter, PD (1991) Fetal and infant growth and impaired glucose-tolerance at age 64. British Medical Journal 303 10191022.CrossRefGoogle ScholarPubMed
Huxley, R, Neil, A & Collins, R (2002) Unravelling the fetal origins hypothesis: is there really an inverse association between birthweight and subsequent blood pressure? Lancet 360 659665.CrossRefGoogle ScholarPubMed
Huxley, RR & Neil, NA (2004) Does maternal nutrition in pregnancy and birth weight influence levels of CHD risk factors in adult life? British Journal of Nutrition 91 459468.CrossRefGoogle ScholarPubMed
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 168175.CrossRefGoogle ScholarPubMed
Kind, KL, Simonetta, G, Clifton, PM, Robinson, JS & Owens, JA (2002) Effect of maternal feed restriction on blood pressure in the adult guinea pig. Experimental Physiology 87 469477.CrossRefGoogle ScholarPubMed
Kramer, MS & Joseph, KS (1996) Enigma of fetal/infant-origins hypothesis. Lancet 348 12541255.CrossRefGoogle ScholarPubMed
Kwong, WY, Wild, AE, Roberts, P, Willis, AC & Fleming, TP (2000) Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and programming of postnatal hypertension. Development 127 41954202.CrossRefGoogle ScholarPubMed
Langley-Evans, AJ, Langley-Evans, SC (2003) Relationship between maternal nutrient intakes in early and late pregnancy and infants weight and proportions at birth. Journal of the Royal Society for the Promotion of Health 123 210216.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (1997 a) Hypertension induced by foetal exposure to a maternal low-protein diet, in the rat, is prevented by pharmacological blockade of maternal glucocorticoid synthesis. Journal of Hypertension 15 537544.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (1997 b) Maternal carbenoxolone treatment lowers birthweight and induces hypertension in the offspring of rats fed a protein-replete diet. Clinical Science 93 423429.CrossRefGoogle ScholarPubMed
Langley-Evans, SC (editor) (2004 a) Experimental models of hypertension and cardiovascular disease. In Fetal Nutrition and Adult Disease: Programming of Chronic Disease through Fetal Exposure to Undernutrition, pp. 129156. Wallingford, Oxon.: CABI.CrossRefGoogle Scholar
Langley-Evans, SC (editor) (2004 b) Fetal programming of adult disease: an overview. In Fetal Nutrition and Adult Disease: Programming of Chronic Disease through Fetal Exposure to Undernutrition, pp. 120. Wallingford, Oxon.: CABI.CrossRefGoogle Scholar
Langley-Evans, SC, Bellinger, L & McMullen, S (2005) Animal models of programming: Early life influences on appetite and feeding behaviour. Maternal and Child Nutrition (In the Press).CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Gardner, DS, Jackson, AA (1996 a) Association of disproportionate growth of fetal rats in late gestation with raised systolic blood pressure in later life. Journal of Reproduction and Fertility 106 307312.CrossRefGoogle ScholarPubMed
Langley-Evans, SC & Jackson, AA (1995) Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets. Comparative Biochemistry and Physiology 110A 223228.CrossRefGoogle Scholar
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. Clinical Nutrition 13 319324.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Phillips, GJ & Jackson, AA (1997) Fetal exposure to low protein maternal diet alters the susceptibility of young adult rats to sulfur dioxide-induced lung injury. Journal of Nutrition 127 202209.Google ScholarPubMed
Langley-Evans, SC, Phillips, GJ, Gardner, DS & Jackson, AA (1996 b) Role of glucocorticoids in programming of maternal-diet-induced hypertension. Journal of Nutritional Biochemistry 7 173178.CrossRefGoogle Scholar
Langley-Evans, SC, Phillips, GJ, Benediktsson, R, Gardner, DS, Edwards, CR, Jackson, AA, Seckl, JR, (1996 c) Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. Placenta 17 169172.CrossRefGoogle ScholarPubMed
Langley-Evans, SC & Sculley, DV (2005) Programming of hepatic antioxidant capacity and oxidative injury in the ageing rat. Mechanisms of Ageing and Development 126 804812.CrossRefGoogle ScholarPubMed
Langley-Evans, SC, Welham, SJM, Sherman, RC, Jackson, AA (1996 d) Weanling rats exposed to maternal low protein diets during discrete periods of gestation exhibit differing severity of hypertension. Clinical Science 91 607615.CrossRefGoogle ScholarPubMed
Law, CM (2002) Significance of birth weight for the future. Archives of Disease in Childhood 86 F7F8.CrossRefGoogle ScholarPubMed
Law, CM, Barker, DJ, Bull, AR & Osmond, C (1991) Maternal and fetal influences on blood pressure. Archives of Disease in Childhood 66 12911295.CrossRefGoogle ScholarPubMed
Lilley, C, Langley-Evans, SC (2005) Fetal programming of adult disease may be induced by oxidative damage and alterations in antioxidant activity. Proceedings of the Nutrition Society 64 81A.Google Scholar
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. Journal of Nutrition 135 13821386.CrossRefGoogle ScholarPubMed
Lucas, A (1991) Programming by early nutrition in man. Ciba Foundation Symposium 156 3850.Google ScholarPubMed
McMullen, S, Langley-Evans, SC (2005) Maternal low-protein diet in rat pregnancy programs blood pressure through sex-specific mechanisms. American Journal of Physiology 288 R85R90.Google ScholarPubMed
McMullen, S, Gardner, DS, Langley-Evans, SC (2004) Prenatal programming of angiotensin II type 2 receptor expression in the rat. British Journal of Nutrition 91 133140.CrossRefGoogle ScholarPubMed
Mackenzie, HS, Lawler, EV & Brenner, BM (1996) Congenital oligonephropathy: The fetal flaw in essential hypertension? Kidney International 55 Suppl. S30S34Google ScholarPubMed
Marchand, MC, Langley-Evans, SC (2001) Intrauterine programming of nephron number: the fetal flaw revisited. Journal of Nephrology 14 327331.Google ScholarPubMed
Mathews, F, Yudkin, P & Neil, A (1999) Influence of maternal nutrition on outcome of pregnancy: prospective cohort study. British Medical Journal 319 339343.CrossRefGoogle ScholarPubMed
Motoike, T, Loughna, S, Perens, E, Roman, BL, Liao, W, Chau, TC et al. (2000) Universal GFP reporter for the study of vascular development. Genesis 28 7581.3.0.CO;2-S>CrossRefGoogle Scholar
Nwagwu, MO, Cook, A, Langley-Evans, SC (2000) Evidence of progressive deterioration of renal function in rats exposed to a maternal low protein diet in utero. British Journal of Nutrition 83 7985.CrossRefGoogle ScholarPubMed
Osmond, C, Barker, DJ & Slattery, JM (1990) Risk of death from cardiovascular disease and chronic bronchitis determined by place of birth in England and Wales. Journal of Epidemiology and Community Health 44 139141.CrossRefGoogle ScholarPubMed
Painter, RC, Roseboom, TJ, van Montfrans, GA, Bossuyt, PM, Krediet, RT, Osmond, C, Barker, DJ & Bleker, OP (2005) Microalbuminuria in adults after prenatal exposure to the Dutch famine. Journal of the American Society for Nephrology 16 189194.CrossRefGoogle Scholar
Petrie, L, Duthie, SJ, Rees, WD & McConnell, JM (2002) Serum concentrations of homocysteine are elevated during early pregnancy in rodent models of fetal programming. British Journal of Nutrition 88 471477.CrossRefGoogle ScholarPubMed
Phillips, DIW, Barker, DJP, Hales, CN, Hirst, S & Osmond, C (1994) Thinness at birth and insulin resistance in adult life. Diabetologia 37 150154.CrossRefGoogle ScholarPubMed
Plagemann, A, Harder, T, Rake, A, Melchior, K, Rohde, W & Dorner, G (2000) Hypothalamic nuclei are malformed in weanling offspring of low protein malnourished rat dams. Journal of Nutrition 130 25822589.CrossRefGoogle ScholarPubMed
Ravelli, AC, van der Meulen, JH, Osmond, C, Barker, DJ & Bleker, OP (1999) Obesity at the age of 50 y in men and women exposed to famine prenatally. American Journal of Clinical Nutrition 70 811816.CrossRefGoogle ScholarPubMed
Ravelli, AC, van der Meulen, JH, Osmond, C, Barker, DJ & Bleker, OP (2000) Infant feeding and adult glucose tolerance, lipid profile, blood pressure, and obesity. Archives of Disease in Childhood 82 248252.CrossRefGoogle ScholarPubMed
Razin, A (1998) CpG methylation, chromatin structure and gene silencing–a three-way connection. EMBO Journal 17 49054908.CrossRefGoogle ScholarPubMed
Rees, WD (2002) Manipulating the sulfur amino acid content of the early diet and its implications for long-term health. Proceedings of the Nutrition Society 61 7177.CrossRefGoogle ScholarPubMed
Reusens, B, Kalbe, L & Remacle, C (2004) Programming of diabetes: experimental models. In Fetal Nutrition and Adult Disease: Programming of Chronic Disease through Fetal Exposure to Undernutrition, pp. 171194 [Langley-Evans, SC, editor]. Wallingford, Oxon.: CABI.CrossRefGoogle Scholar
Roseboom, TJ, van der Meulen, JH, Osmond, C, Barker, DJ, Ravelli, AC, Schroeder-Tanka, JM, van Montfrans, GA, Michels, RP & Bleker, OP (2000) Coronary heart disease after prenatal exposure to the Dutch famine, 1944–45. Heart 84 595598.CrossRefGoogle Scholar
Roseboom, TJ, van der Meulen, JH, Ravelli, AC, Osmond, C, Barker, DJ & Bleker, OP (2001) Effects of prenatal exposure to the Dutch famine on adult disease in later life: an overview. Twin Research 4 293298.CrossRefGoogle Scholar
Sayer, AA, Dunn, RL, Langley-Evans, SC & Cooper, C (2001) Prenatal exposure to a maternal low protein diet shortens life span in rats. Gerontology 47 914.CrossRefGoogle Scholar
Snoeck, A, Remacle, C, Reusens, B & Hoet, JJ (1990) Effect of a low protein diet during pregnancy on the fetal rat endocrine pancreas. Biology of the Neonate 57 107118.CrossRefGoogle ScholarPubMed
Stanner, SA & Yudkin, JS (2001) Fetal programming and the Leningrad Siege study. Twin Research 4 287292.CrossRefGoogle ScholarPubMed
Stein, A (2004) Birthweight and the development of overweight and obesity. In Fetal Nutrition and Adult Disease: Programming of Chronic Disease through Fetal Exposure to Undernutrition, pp. 195210 [Langley-Evans, SC, editor]. Wallingford, Oxon.: CABI.CrossRefGoogle Scholar
Sutherland, FJ & Hearse, DS (2000) The isolated blood and perfusion fluid perfused heart. Pharmacological Research 41 613627.CrossRefGoogle ScholarPubMed
Vickers, MH, Breier, BH, Cutfield, WS, Hofman, PL & Gluckman, PD (2000) Fetal origins of hyperphagia, obesity, and hypertension and postnatal amplification by hypercaloric nutrition. American Journal of Physiology 279 E83E87.Google ScholarPubMed
Vickers, MH, Breier, BH, McCarthy, D & Gluckman, PD (2003) Sedentary behavior during postnatal life is determined by the prenatal environment and exacerbated by postnatal hypercaloric nutrition. American Journal of Physiology 285 R271R273.Google ScholarPubMed
Waterland, RA & Jirtle, RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Molecular and Cellular Biology 23 52935300.CrossRefGoogle ScholarPubMed
Weaver, IC, Cervoni, N, Champagne, FA, D'Alessio, AC, Sharma, S, Seckl, JR, Dymov, S, Szyf, M & Meaney, MJ (2004) Epigenetic programming by maternal behavior. Nature Neuroscience 7 847854.CrossRefGoogle ScholarPubMed
Woodall, SM, Johnston, BM, Breier, BH & Gluckman, PD (1996) Chronic maternal undernutrition in the rat leads to delayed postnatal growth and elevated blood pressure of offspring. Pediatric Research 40 438443.CrossRefGoogle ScholarPubMed
Young, L, Rees, WD & Sinclair, KD (2004) Programming in the pre-implantation embryo. In Fetal Nutrition and Adult Disease: Programming of Chronic Disease through Fetal Exposure to Undernutrition, pp. 333352 [Langley-Evans, SC, editor]. Wallingford, Oxon.: CABI.CrossRefGoogle Scholar