HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (190) Citing Articles via Google Scholar Google Scholar Articles by Mcmillen, I. C. Articles by Robinson, J. S. Search for Related Content PubMed PubMed Citation Articles by Mcmillen, I. C. Articles by Robinson, J. S.

Developmental Origins of the Metabolic Syndrome: Prediction, Plasticity, and Programming

Discipline of Physiology, School of Molecular and Biomedical Sciences, and Department Obstetrics and Gynaecology, University of Adelaide, Adelaide, Australia

The "fetal" or "early" origins of adult disease hypothesis was originally put forward by David Barker and colleagues and stated that environmental factors, particularly nutrition, act in early life to program the risks for adverse health outcomes in adult life. This hypothesis has been supported by a worldwide series of epidemiological studies that have provided evidence for the association between the perturbation of the early nutritional environment and the major risk factors (hypertension, insulin resistance, and obesity) for cardiovascular disease, diabetes, and the metabolic syndrome in adult life. It is also clear from experimental studies that a range of molecular, cellular, metabolic, neuroendocrine, and physiological adaptations to changes in the early nutritional environment result in a permanent alteration of the developmental pattern of cellular proliferation and differentiation in key tissue and organ systems that result in pathological consequences in adult life. This review focuses on those experimental studies that have investigated the critical windows during which perturbations of the intrauterine environment have major effects, the nature of the epigenetic, structural, and functional adaptive responses which result in a permanent programming of cardiovascular and metabolic function, and the role of the interaction between the pre- and postnatal environment in determining final health outcomes.

This article has been cited by other articles:

				P. D. Gluckman, M. A. Hanson, C. Cooper, and K. L. Thornburg Effect of In Utero and Early-Life Conditions on Adult Health and Disease N. Engl. J. Med., July 3, 2008; 359(1): 61 - 73. [Full Text] [PDF]

				A. L. Siebel, A. Mibus, M. J. De Blasio, K. T. Westcott, M. J. Morris, L. Prior, J. A. Owens, and M. E. Wlodek Improved Lactational Nutrition and Postnatal Growth Ameliorates Impairment of Glucose Tolerance by Uteroplacental Insufficiency in Male Rat Offspring Endocrinology, June 1, 2008; 149(6): 3067 - 3076. [Abstract] [Full Text] [PDF]

				M. P. Koeners, B. Braam, D. M. van der Giezen, R. Goldschmeding, and J. A. Joles A perinatal nitric oxide donor increases renal vascular resistance and ameliorates hypertension and glomerular injury in adult fawn-hooded hypertensive rats Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2008; 294(6): R1847 - R1855. [Abstract] [Full Text] [PDF]

				T. Bishop, D. Gallagher, A. Pascual, C. A. Lygate, J. P. de Bono, L. G. Nicholls, P. Ortega-Saenz, H. Oster, B. Wijeyekoon, A. I. Sutherland, et al. Abnormal Sympathoadrenal Development and Systemic Hypotension in PHD3-/- Mice Mol. Cell. Biol., May 15, 2008; 28(10): 3386 - 3400. [Abstract] [Full Text] [PDF]

				K Rajaleid, O Manor, and I Koupil Does the strength of the association between foetal growth rate and ischaemic heart disease mortality differ by social circumstances in early or later life? J. Epidemiol. Community Health, May 1, 2008; 62(5): e6 - e6. [Abstract] [Full Text] [PDF]

				M. Ceelen, M. M. van Weissenbruch, J. P. W. Vermeiden, F. E. van Leeuwen, and H. A. Delemarre-van de Waal Cardiometabolic Differences in Children Born After in Vitro Fertilization: Follow-Up Study J. Clin. Endocrinol. Metab., May 1, 2008; 93(5): 1682 - 1688. [Abstract] [Full Text] [PDF]

				J. A. Duffield, T. Vuocolo, R. Tellam, B. S. Yuen, B. S. Muhlhausler, and I. C. McMillen Placental restriction of fetal growth decreases IGF1 and leptin mRNA expression in the perirenal adipose tissue of late gestation fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2008; 294(5): R1413 - R1419. [Abstract] [Full Text] [PDF]

				A. J. Watkins, A. Wilkins, C. Cunningham, V. H. Perry, M. J. Seet, C. Osmond, J. J. Eckert, C. Torrens, F. R. A. Cagampang, J. Cleal, et al. Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring J. Physiol., April 15, 2008; 586(8): 2231 - 2244. [Abstract] [Full Text] [PDF]

				E. Kajantie, D. J P Barker, C. Osmond, T. Forsen, and J. G Eriksson Growth before 2 years of age and serum lipids 60 years later: The Helsinki Birth Cohort Study Int. J. Epidemiol., April 1, 2008; 37(2): 280 - 289. [Abstract] [Full Text] [PDF]

				J. S. Gilbert Sex, Salt, and Senescence: Sorting Out Mechanisms of the Developmental Origins of Hypertension Hypertension, April 1, 2008; 51(4): 997 - 999. [Full Text] [PDF]

				W. V. Ingman and R. L. Jones Cytokine knockouts in reproduction: the use of gene ablation to dissect roles of cytokines in reproductive biology Hum. Reprod. Update, March 1, 2008; 14(2): 179 - 192. [Abstract] [Full Text] [PDF]

				K. Shankar, A. Harrell, X. Liu, J. M. Gilchrist, M. J. J. Ronis, and T. M. Badger Maternal obesity at conception programs obesity in the offspring Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R528 - R538. [Abstract] [Full Text] [PDF]

				A. J Watkins, E. Ursell, R. Panton, T. Papenbrock, L. Hollis, C. Cunningham, A. Wilkins, V. H. Perry, B. Sheth, W. Y. Kwong, et al. Adaptive Responses by Mouse Early Embryos to Maternal Diet Protect Fetal Growth but Predispose to Adult Onset Disease Biol Reprod, February 1, 2008; 78(2): 299 - 306. [Abstract] [Full Text] [PDF]

				L. Schaffer, T. Burkhardt, D. Muller-Vizentini, M. Rauh, M. Tomaske, R. A. Mieth, U. Bauersfeld, and E. Beinder Cardiac autonomic balance in small-for-gestational-age neonates Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H884 - H890. [Abstract] [Full Text] [PDF]

				J. Wang, L. Chen, D. Li, Y. Yin, X. Wang, P. Li, L. J. Dangott, W. Hu, and G. Wu Intrauterine Growth Restriction Affects the Proteomes of the Small Intestine, Liver, and Skeletal Muscle in Newborn Pigs J. Nutr., January 1, 2008; 138(1): 60 - 66. [Abstract] [Full Text] [PDF]

				K. D. Sinclair, C. Allegrucci, R. Singh, D. S. Gardner, S. Sebastian, J. Bispham, A. Thurston, J. F. Huntley, W. D. Rees, C. A. Maloney, et al. DNA methylation, insulin resistance, and blood pressure in offspring determined by maternal periconceptional B vitamin and methionine status PNAS, December 4, 2007; 104(49): 19351 - 19356. [Abstract] [Full Text] [PDF]

				D. O Mook-Kanamori, J J Miranda Geelhoed, E. A P Steegers, J. C M Witteman, A. Hofman, H. A Moll, C. M van Duijn, A. C S Hokken-Koelega, and V. W V Jaddoe Insulin gene variable number of tandem repeats is not associated with weight from fetal life until infancy: the Generation R Study Eur. J. Endocrinol., December 1, 2007; 157(6): 741 - 748. [Abstract] [Full Text] [PDF]

				P. D Gluckman Evolving a definition of disease Arch. Dis. Child., December 1, 2007; 92(12): 1053 - 1054. [Full Text] [PDF]

				M. P. Koeners, E. E. van Faassen, S. Wesseling, M. de Sain-van der Velden, H. A. Koomans, B. Braam, and J. A. Joles Maternal Supplementation With Citrulline Increases Renal Nitric Oxide in Young Spontaneously Hypertensive Rats and Has Long-Term Antihypertensive Effects Hypertension, December 1, 2007; 50(6): 1077 - 1084. [Abstract] [Full Text] [PDF]

				M. M. Davis, B. Gance-Cleveland, S. Hassink, R. Johnson, G. Paradis, and K. Resnicow Recommendations for Prevention of Childhood Obesity Pediatrics, December 1, 2007; 120(Supplement_4): S229 - S253. [Abstract] [Full Text] [PDF]

				P. Poulsen, J. F.P. Wojtaszewski, E. A. Richter, H. Beck-Nielsen, and A. Vaag Low Birth Weight and Zygosity Status Is Associated With Defective Muscle Glycogen and Glycogen Synthase Regulation in Elderly Twins Diabetes, November 1, 2007; 56(11): 2710 - 2714. [Abstract] [Full Text] [PDF]

				M G Gnanalingham, P Williams, V Wilson, J Bispham, M A Hyatt, A Pellicano, H Budge, T Stephenson, and M E Symonds Nutritional manipulation between early to mid-gestation: effects on uncoupling protein-2, glucocorticoid sensitivity, IGF-I receptor and cell proliferation but not apoptosis in the ovine placenta Reproduction, October 1, 2007; 134(4): 615 - 623. [Abstract] [Full Text] [PDF]

				J. S. Dyer, C. R. Rosenfeld, J. Rice, M. Rice, and D. S. Hardin Insulin Resistance in Hispanic Large-for-Gestational-Age Neonates at Birth J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3836 - 3843. [Abstract] [Full Text] [PDF]

				M. A. Hyatt, H. Budge, D. Walker, T. Stephenson, and M. E. Symonds Ontogeny and Nutritional Programming of the Hepatic Growth Hormone-Insulin-Like Growth Factor-Prolactin Axis in the Sheep Endocrinology, October 1, 2007; 148(10): 4754 - 4760. [Abstract] [Full Text] [PDF]

				N. B. Ojeda, D. Grigore, E. B. Robertson, and B. T. Alexander Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted Offspring Hypertension, October 1, 2007; 50(4): 679 - 685. [Abstract] [Full Text] [PDF]

				M. Gamborg, L. Byberg, F. Rasmussen, P. K. Andersen, J. L. Baker, C. Bengtsson, D. Canoy, W. Droyvold, J. G. Eriksson, T. Forsen, et al. Birth Weight and Systolic Blood Pressure in Adolescence and Adulthood: Meta-Regression Analysis of Sex- and Age-specific Results from 20 Nordic Studies Am. J. Epidemiol., September 15, 2007; 166(6): 634 - 645. [Abstract] [Full Text] [PDF]

				M. Ceelen, M. M. van Weissenbruch, J. C. Roos, J. P. W. Vermeiden, F. E. van Leeuwen, and H. A. Delemarre-van de Waal Body Composition in Children and Adolescents Born after in Vitro Fertilization or Spontaneous Conception J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3417 - 3423. [Abstract] [Full Text] [PDF]

				J. Ferezou-Viala, A.-F. Roy, C. Serougne, D. Gripois, M. Parquet, V. Bailleux, A. Gertler, B. Delplanque, J. Djiane, M. Riottot, et al. Long-term consequences of maternal high-fat feeding on hypothalamic leptin sensitivity and diet-induced obesity in the offspring Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2007; 293(3): R1056 - R1062. [Abstract] [Full Text] [PDF]

				D. C. Dolinoy, D. Huang, and R. L. Jirtle Maternal nutrient supplementation counteracts bisphenol A-induced DNA hypomethylation in early development PNAS, August 7, 2007; 104(32): 13056 - 13061. [Abstract] [Full Text] [PDF]

				O. Khorram, N. Khorram, M. Momeni, G. Han, J. Halem, M. Desai, and M. G. Ross Maternal undernutrition inhibits angiogenesis in the offspring: a potential mechanism of programmed hypertension Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R745 - R753. [Abstract] [Full Text] [PDF]

				G. N. Luheshi and C. Rummel Is programming of weight regulation immune to neonatal inflammation? Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2007; 293(2): R578 - R580. [Full Text] [PDF]

				P. D. Gluckman, K. A. Lillycrop, M. H. Vickers, A. B. Pleasants, E. S. Phillips, A. S. Beedle, G. C. Burdge, and M. A. Hanson Metabolic plasticity during mammalian development is directionally dependent on early nutritional status PNAS, July 31, 2007; 104(31): 12796 - 12800. [Abstract] [Full Text] [PDF]

				N. Igosheva, P. D. Taylor, L. Poston, and V. Glover Prenatal stress in the rat results in increased blood pressure responsiveness to stress and enhanced arterial reactivity to neuropeptide Y in adulthood J. Physiol., July 15, 2007; 582(2): 665 - 674. [Abstract] [Full Text] [PDF]

				J. L. Morrison, K. J. Botting, J. L. Dyer, S. J. Williams, K. L. Thornburg, and I. C. McMillen Restriction of placental function alters heart development in the sheep fetus Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R306 - R313. [Abstract] [Full Text] [PDF]

				L. A. Cox and P. W. Nathanielsz Importance of genetic differences in developmental programming: gene by environment interactions in models of maternal dietary restriction J. Physiol., June 1, 2007; 581(2): 421 - 422. [Full Text] [PDF]

				A. Erhuma, A. M. Salter, D. V. Sculley, S. C. Langley-Evans, and A. J. Bennett Prenatal exposure to a low-protein diet programs disordered regulation of lipid metabolism in the aging rat Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1702 - E1714. [Abstract] [Full Text] [PDF]

				N. M. Thompson, A. M. Norman, S. S. Donkin, R. R. Shankar, M. H. Vickers, J. L. Miles, and B. H. Breier Prenatal and Postnatal Pathways to Obesity: Different Underlying Mechanisms, Different Metabolic Outcomes Endocrinology, May 1, 2007; 148(5): 2345 - 2354. [Abstract] [Full Text] [PDF]

				L. Sedova, O. Seda, L. Kazdova, B. Chylikova, P. Hamet, J. Tremblay, V. Kren, and D. Krenova Sucrose feeding during pregnancy and lactation elicits distinct metabolic response in offspring of an inbred genetic model of metabolic syndrome Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1318 - E1324. [Abstract] [Full Text] [PDF]

				S. M. MacLaughlin, S. K. Walker, D. O. Kleemann, J. P. Sibbons, D. N. Tosh, S. Gentili, C. L. Coulter, and I. C. McMillen Impact of Periconceptional Undernutrition on Adrenal Growth and Adrenal Insulin-Like Growth Factor and Steroidogenic Enzyme Expression in the Sheep Fetus during Early Pregnancy Endocrinology, April 1, 2007; 148(4): 1911 - 1920. [Abstract] [Full Text] [PDF]

				E. Lebenthal and D. M. Bier Novel Concepts in the Developmental Origins of Adult Health and Disease J. Nutr., April 1, 2007; 137(4): 1073 - 1075. [Full Text] [PDF]

				M. G. Frasch, T. Muller, C. Wicher, C. Weiss, M. Lohle, K. Schwab, H. Schubert, P. W. Nathanielsz, O. W. Witte, and M. Schwab Fetal body weight and the development of the control of the cardiovascular system in fetal sheep J. Physiol., March 15, 2007; 579(3): 893 - 907. [Abstract] [Full Text] [PDF]

				A. M. Nuyt and M. Szyf Developmental Programming Through Epigenetic Changes Circ. Res., March 2, 2007; 100(4): 452 - 455. [Full Text] [PDF]

				G. Cambonie, B. Comte, C. Yzydorczyk, T. Ntimbane, N. Germain, N. L. O. Le, P. Pladys, C. Gauthier, I. Lahaie, D. Abran, et al. Antenatal antioxidant prevents adult hypertension, vascular dysfunction, and microvascular rarefaction associated with in utero exposure to a low-protein diet Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1236 - R1245. [Abstract] [Full Text] [PDF]

				B. N. Van Vliet and L. L. Chafe Maternal Endothelial Nitric Oxide Synthase Genotype Influences Offspring Blood Pressure and Activity in Mice Hypertension, March 1, 2007; 49(3): 556 - 562. [Abstract] [Full Text] [PDF]

				N. B. Ojeda, D. Grigore, L. L. Yanes, R. Iliescu, E. B. Robertson, H. Zhang, and B. T. Alexander Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R758 - R763. [Abstract] [Full Text] [PDF]

				O. Khorram, M. Momeni, M. Desai, and M. G. Ross Nutrient Restriction In Utero Induces Remodeling of the Vascular Extracellular Matrix in Rat Offspring Reproductive Sciences, January 1, 2007; 14(1): 73 - 80. [Abstract] [PDF]

				H. Dickinson, D. W. Walker, E. M. Wintour, and K. Moritz Maternal dexamethasone treatment at midgestation reduces nephron number and alters renal gene expression in the fetal spiny mouse Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R453 - R461. [Abstract] [Full Text] [PDF]

				E. Landmann, F. Geller, J. Schilling, S. Rudloff, E. Foeller-Gaudier, and L. Gortner Absence of the Wild-type Allele (192 Base Pairs) of a Polymorphism in the Promoter Region of the IGF-I Gene but Not a Polymorphism in the Insulin Gene Variable Number of Tandem Repeat Locus Is Associated With Accelerated Weight Gain in Infancy Pediatrics, December 1, 2006; 118(6): 2374 - 2379. [Abstract] [Full Text] [PDF]

				G. Iniguez, K. Ong, R. Bazaes, A. Avila, T. Salazar, D. Dunger, and V. Mericq Longitudinal Changes in Insulin-Like Growth Factor-I, Insulin Sensitivity, and Secretion from Birth to Age Three Years in Small-for-Gestational-Age Children J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4645 - 4649. [Abstract] [Full Text] [PDF]

				F. Rahnama, F. Shafiei, P. D. Gluckman, M. D. Mitchell, and P. E. Lobie Epigenetic Regulation of Human Trophoblastic Cell Migration and Invasion Endocrinology, November 1, 2006; 147(11): 5275 - 5283. [Abstract] [Full Text] [PDF]

				C. Thone-Reineke, P. Kalk, M. Dorn, S. Klaus, K. Simon, T. Pfab, M. Godes, P. Persson, T. Unger, and B. Hocher High-protein nutrition during pregnancy and lactation programs blood pressure, food efficiency, and body weight of the offspring in a sex-dependent manner Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R1025 - R1030. [Abstract] [Full Text] [PDF]

				C. Yzydorczyk, F. Gobeil Jr., G. Cambonie, I. Lahaie, N. L. O. Le, S. Samarani, A. Ahmad, J. C. Lavoie, L. L. Oligny, P. Pladys, et al. Exaggerated vasomotor response to ANG II in rats with fetal programming of hypertension associated with exposure to a low-protein diet during gestation Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R1060 - R1068. [Abstract] [Full Text] [PDF]

				M. Bursztyn, M.-L. Gross, T. Goltser-Dubner, N. Koleganova, T. Birman, Y. Smith, and I. Ariel Adult Hypertension in Intrauterine Growth-Restricted Offspring of Hyperinsulinemic Rats: Evidence of Subtle Renal Damage Hypertension, October 1, 2006; 48(4): 717 - 723. [Abstract] [Full Text] [PDF]

				M. I. Hernandez, A. Martinez, T. Capurro, V. Pena, L. Trejo, A. Avila, T. Salazar, S. Asenjo, G. Iniguez, and V. Mericq Comparison of Clinical, Ultrasonographic, and Biochemical Differences at the Beginning of Puberty in Healthy Girls Born Either Small for Gestational Age or Appropriate for Gestational Age: Preliminary Results J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3377 - 3381. [Abstract] [Full Text] [PDF]

				G. Wu, F. W. Bazer, J. M. Wallace, and T. E. Spencer BOARD-INVITED REVIEW: Intrauterine growth retardation: Implications for the animal sciences J Anim Sci, September 1, 2006; 84(9): 2316 - 2337. [Abstract] [Full Text] [PDF]

				W. Y. Kwong, D. J Miller, E. Ursell, A. E Wild, A. P Wilkins, C. Osmond, F. W Anthony, and T. P Fleming Imprinted gene expression in the rat embryo-fetal axis is altered in response to periconceptional maternal low protein diet. Reproduction, August 1, 2006; 132(2): 265 - 277. [Abstract] [Full Text] [PDF]

				D. S. Fernandez-Twinn, S. Ekizoglou, A. Wayman, C. J. Petry, and S. E. Ozanne Maternal low-protein diet programs cardiac beta-adrenergic response and signaling in 3-mo-old male offspring Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R429 - R436. [Abstract] [Full Text] [PDF]

				J. L. Segar, R. D. Roghair, E. M. Segar, M. C. Bailey, T. D. Scholz, and F. S. Lamb Early gestation dexamethasone alters baroreflex and vascular responses in newborn lambs before hypertension Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R481 - R488. [Abstract] [Full Text] [PDF]

F. H. Bloomfield, P. L. van Zijl, M. K. Ba