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Semin Reprod Med 2011; 29(3): 197-210
DOI: 10.1055/s-0031-1275520
© Thieme Medical Publishers

The Early Origins of Cardiovascular Health and Disease: Who, When, and How

Christian F. Rueda-Clausen1 , 3 , 4 , 5 , Jude S. Morton2 , 3 , 4 , 5 , Sandra T. Davidge1 , 2 , 3 , 4 , 5
  • 1Department of Physiology, University of Alberta, Edmonton, Canada
  • 2Department of Obstetrics and Gynecology, University of Alberta, Edmonton, Canada
  • 3Women and Children's Health Research Institute (WCHRI), University of Alberta, Edmonton, Canada
  • 4Cardiovascular Research Centre, University of Alberta, Edmonton, Canada
  • 5Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada
Further Information

Publication History

Publication Date:
27 June 2011 (online)

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ABSTRACT

Almost 30 years ago, a series of epidemiological studies popularized the early programming theory that had resulted from observed associations between low birthweight and increased cardiovascular morbidity and mortality later in life. Since then, several clinical and experimental models have been created to understand the principles and mechanisms of this fascinating phenomenon and describe its relevance to the pathophysiology of cardiovascular and many other chronic diseases. Despite the growing body of published evidence, the specific mechanisms mediating early programming effects are still elusive. Moreover, many controversial issues have arisen regarding the characteristics of the most commonly used clinical and experimental models, the existence of potential windows of susceptibility for different organs, and the presence of sex differences in its pathophysiology. Therefore, this review synthesizes some of the antecedents behind the early programming theory and discusses some of the controversial issues surrounding it. Early programming has been extensively linked to several chronic diseases; however, for the purposes of this review we have concentrated on the potential role of this entity in the pathophysiology of chronic cardiovascular diseases.

KEYWORDS

Fetal - programming - cardiovascular - models - window of susceptibility - sex

REFERENCES

  • 1 Mayr E. Commemorating the 20th century Darwin: Ernst Mayr's words and thoughts, five years later. Interview by Rob J. Kulathinal.  Genome. 2010;  53 (2) 157-159
    CrossrefPubMedGoogle Scholar
  • 2 Brakefield P M, Gates J, Keys D et al.. Development, plasticity and evolution of butterfly eyespot patterns.  Nature. 1996;  384 (6606) 236-242
    CrossrefPubMedGoogle Scholar
  • 3 Kutschera U. Charles Darwin's Origin of Species, directional selection, and the evolutionary sciences today.  Naturwissenschaften. 2009;  96 (11) 1247-1263
    CrossrefPubMedGoogle Scholar
  • 4 The scientific consensus around evolution is overwhelming. Appendix: Frequently asked questions. In: Science and Creationism: A View from the National Academy of Sciences. 2nd ed. Washington, DC: National Academy Press; 1999
    Google Scholar
  • 5 Gilbert S F. The genome in its ecological context: philosophical perspectives on interspecies epigenesis.  Ann N Y Acad Sci. 2002;  981 202-218
    PubMedGoogle Scholar
  • 6 Gilbert S F. Ecological developmental biology: developmental biology meets the real world.  Dev Biol. 2001;  233 (1) 1-12
    CrossrefPubMedGoogle Scholar
  • 7 Unterberger A, Szyf M, Nathanielsz P W, Cox L A. Organ and gestational age effects of maternal nutrient restriction on global methylation in fetal baboons.  J Med Primatol. 2009;  38 (4) 219-227
    CrossrefPubMedGoogle Scholar
  • 8 McFall-Ngai M J. Unseen forces: the influence of bacteria on animal development.  Dev Biol. 2002;  242 (1) 1-14
    CrossrefPubMedGoogle Scholar
  • 9 Hertwig O. Zeit- und Streitfragen der Biologie I. Prašformation oder Epigenese? Grundzušge einer Entwicklungstheorie der Organismen. In: Jena G F, ed., Mitchell P C, trans. Translated as The Biological Problem of Today: Preformation or Epigenesis?. New York, NY: Macmillan; 1894
    Google Scholar
  • 10 Barker D J. The origins of the developmental origins theory.  J Intern Med. 2007;  261 (5) 412-417
    CrossrefPubMedGoogle Scholar
  • 11 Kermack W O, Mckendrick A G, McKinlay P L. Death rates in Great Britain and Sweden; some general regularities and their significance.  Lancet. 1934;  i 698-703
    PubMedGoogle Scholar
  • 12 Rose G. Familial patterns in ischaemic heart disease.  Br J Prev Soc Med. 1964;  18 75-80
    PubMedGoogle Scholar
  • 13 Ravelli G P, Stein Z A, Susser M W. Obesity in young men after famine exposure in utero and early infancy.  N Engl J Med. 1976;  295 (7) 349-353
    CrossrefPubMedGoogle Scholar
  • 14 Forsdahl A. Are poor living conditions in childhood and adolescence an important risk factor for arteriosclerotic heart disease?.  Br J Prev Soc Med. 1977;  31 (2) 91-95
    PubMedGoogle Scholar
  • 15 Barker D J. The fetal and infant origins of adult disease.  BMJ. 1990;  301 (6761) 1111
    CrossrefPubMedGoogle Scholar
  • 16 Barker D J, Osmond C, Law C M. The intrauterine and early postnatal origins of cardiovascular disease and chronic bronchitis.  J Epidemiol Community Health. 1989;  43 (3) 237-240
    CrossrefPubMedGoogle Scholar
  • 17 Soto A M, Rubin B S, Sonnenschein C. Interpreting endocrine disruption from an integrative biology perspective.  Mol Cell Endocrinol. 2009;  304 (1–2) 3-7
    CrossrefPubMedGoogle Scholar
  • 18 Joss-Moore L A, Lane R H. The developmental origins of adult disease.  Curr Opin Pediatr. 2009;  21 (2) 230-234
    CrossrefPubMedGoogle Scholar
  • 19 Barker D J. In utero programming of cardiovascular disease.  Theriogenology. 2000;  53 (2) 555-574
    CrossrefPubMedGoogle Scholar
  • 20 Fall C H, Barker D J. The fetal origins of coronary heart disease and non-insulin dependent diabetes in India.  Indian Pediatr. 1997;  34 (1) 5-8
    PubMedGoogle Scholar
  • 21 Barker D J. Fetal origins of coronary heart disease.  Br Heart J. 1993;  69 (3) 195-196
    CrossrefPubMedGoogle Scholar
  • 22 Barker D J, Osmond C, Simmonds S J, Wield G A. The relation of small head circumference and thinness at birth to death from cardiovascular disease in adult life.  BMJ. 1993;  306 (6875) 422-426
    CrossrefPubMedGoogle Scholar
  • 23 Holland M L, Kitzman H, Veazie P. The effects of stress on birth weight in low-income, unmarried black women.  Womens Health Issues. 2009;  19 (6) 390-397
    CrossrefPubMedGoogle Scholar
  • 24 Li G, Bae S, Zhang L. Effect of prenatal hypoxia on heat stress-mediated cardioprotection in adult rat heart.  Am J Physiol Heart Circ Physiol. 2004;  286 (5) H1712-H1719
    CrossrefPubMedGoogle Scholar
  • 25 Han H C, Austin K J, Nathanielsz P W, Ford S P, Nijland M J, Hansen T R. Maternal nutrient restriction alters gene expression in the ovine fetal heart.  J Physiol. 2004;  558 (Pt 1) 111-121
    CrossrefPubMedGoogle Scholar
  • 26 Bogdarina I, Murphy H C, Burns S P, Clark A J. Investigation of the role of epigenetic modification of the rat glucokinase gene in fetal programming.  Life Sci. 2004;  74 (11) 1407-1415
    CrossrefPubMedGoogle Scholar
  • 27 Bertram C E, Hanson M A. Animal models and programming of the metabolic syndrome.  Br Med Bull. 2001;  60 103-121
    CrossrefPubMedGoogle Scholar
  • 28 Gilbert S F. Mechanisms for the environmental regulation of gene expression: ecological aspects of animal development.  J Biosci. 2005;  30 (1) 65-74
    CrossrefPubMedGoogle Scholar
  • 29 Schreuder M F, Nauta J. Prenatal programming of nephron number and blood pressure.  Kidney Int. 2007;  72 (3) 265-268
    CrossrefPubMedGoogle Scholar
  • 30 Corstius H B, Zimanyi M A, Maka N et al.. Effect of intrauterine growth restriction on the number of cardiomyocytes in rat hearts.  Pediatr Res. 2005;  57 (6) 796-800
    CrossrefPubMedGoogle Scholar
  • 31 Morrison J L, Botting K J, Dyer J L, Williams S J, Thornburg K L, McMillen I C. Restriction of placental function alters heart development in the sheep fetus.  Am J Physiol Regul Integr Comp Physiol. 2007;  293 (1) R306-R313
    CrossrefPubMedGoogle Scholar
  • 32 Soonpaa M H, Kim K K, Pajak L, Franklin M, Field L J. Cardiomyocyte DNA synthesis and binucleation during murine development.  Am J Physiol. 1996;  271 (5 Pt 2) H2183-H2189
    PubMedGoogle Scholar
  • 33 Clubb Jr F J, Bishop S P. Formation of binucleated myocardial cells in the neonatal rat. An index for growth hypertrophy.  Lab Invest. 1984;  50 (5) 571-577
    PubMedGoogle Scholar
  • 34 Woodcock E A, Matkovich S J. Cardiomyocytes structure, function and associated pathologies.  Int J Biochem Cell Biol. 2005;  37 (9) 1746-1751
    CrossrefPubMedGoogle Scholar
  • 35 Cheema K K, Dent M R, Saini H K, Aroutiounova N, Tappia P S. Prenatal exposure to maternal undernutrition induces adult cardiac dysfunction.  Br J Nutr. 2005;  93 (4) 471-477
    CrossrefPubMedGoogle Scholar
  • 36 Luyckx V A, Brenner B M. Low birth weight, nephron number, and kidney disease.  Kidney Int Suppl. 2005;  (97) S68-S77
    PubMedGoogle Scholar
  • 37 Thomas R, Kaskel F J. It's not over till the last glomerulus forms.  Kidney Int. 2009;  76 (4) 361-363
    CrossrefPubMedGoogle Scholar
  • 38 Lerma E V. Anatomic and physiologic changes of the aging kidney.  Clin Geriatr Med. 2009;  25 (3) 325-329
    CrossrefPubMedGoogle Scholar
  • 39 Wlodek M E, Westcott K, Siebel A L, Owens J A, Moritz K M. Growth restriction before or after birth reduces nephron number and increases blood pressure in male rats.  Kidney Int. 2008;  74 (2) 187-195
    CrossrefPubMedGoogle Scholar
  • 40 Allen N D. Temporal and epigenetic regulation of neurodevelopmental plasticity.  Philos Trans R Soc Lond B Biol Sci. 2008;  363 (1489) 23-38
    PubMedGoogle Scholar
  • 41 Clarke I J, Scaramuzzi R J, Short R V. Effects of testosterone implants in pregnant ewes on their female offspring.  J Embryol Exp Morphol. 1976;  36 (1) 87-99
    PubMedGoogle Scholar
  • 42 Savabieasfahani M, Lee J S, Herkimer C, Sharma T P, Foster D L, Padmanabhan V. Fetal programming: testosterone exposure of the female sheep during midgestation disrupts the dynamics of its adult gonadotropin secretion during the periovulatory period.  Biol Reprod. 2005;  72 (1) 221-229
    CrossrefPubMedGoogle Scholar
  • 43 Padmanabhan V, Manikkam M, Recabarren S, Foster D. Prenatal testosterone excess programs reproductive and metabolic dysfunction in the female.  Mol Cell Endocrinol. 2006;  246 (1–2) 165-174
    CrossrefPubMedGoogle Scholar
  • 44 New M I, Carlson A, Obeid J et al.. Prenatal diagnosis for congenital adrenal hyperplasia in 532 pregnancies.  J Clin Endocrinol Metab. 2001;  86 (12) 5651-5657
    CrossrefPubMedGoogle Scholar
  • 45 Bhupathy P, Haines C D, Leinwand L A. Influence of sex hormones and phytoestrogens on heart disease in men and women.  Womens Health (Lond Engl). 2010;  6 (1) 77-95
    CrossrefPubMedGoogle Scholar
  • 46 Bull J J, Vogt R C. Temperature-dependent sex determination in turtles.  Science. 1979;  206 (4423) 1186-1188
    CrossrefPubMedGoogle Scholar
  • 47 Yang X, Zheng J, Na R et al.. Degree of sex differentiation of genetic female chicken treated with different doses of an aromatase inhibitor.  Sex Dev. 2008;  2 (6) 309-315
    CrossrefPubMedGoogle Scholar
  • 48 Crews D, Bergeron J M. Role of reductase and aromatase in sex determination in the red-eared slider (Trachemys scripta), a turtle with temperature-dependent sex determination.  J Endocrinol. 1994;  143 (2) 279-289
    CrossrefPubMedGoogle Scholar
  • 49 Waterland R A, Lin J R, Smith C A, Jirtle R L. Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus.  Hum Mol Genet. 2006;  15 (5) 705-716
    CrossrefPubMedGoogle Scholar
  • 50 Waterland R A, Jirtle R L. Early nutrition, epigenetic changes at transposons and imprinted genes, and enhanced susceptibility to adult chronic diseases.  Nutrition. 2004;  20 (1) 63-68
    CrossrefPubMedGoogle Scholar
  • 51 Waterland R A, Jirtle R L. Transposable elements: targets for early nutritional effects on epigenetic gene regulation.  Mol Cell Biol. 2003;  23 (15) 5293-5300
    CrossrefPubMedGoogle Scholar
  • 52 Dolinoy D C, Weidman J R, Waterland R A, Jirtle R L. Maternal genistein alters coat color and protects Avy mouse offspring from obesity by modifying the fetal epigenome.  Environ Health Perspect. 2006;  114 (4) 567-572
    CrossrefPubMedGoogle Scholar
  • 53 Schumacher B, Garinis G A, Hoeijmakers J H. Age to survive: DNA damage and aging.  Trends Genet. 2008;  24 (2) 77-85
    CrossrefPubMedGoogle Scholar
  • 54 Garinis G A, van der Horst G T, Vijg J, Hoeijmakers J H. DNA damage and ageing: new-age ideas for an age-old problem.  Nat Cell Biol. 2008;  10 (11) 1241-1247
    CrossrefPubMedGoogle Scholar
  • 55 Hasty P, Campisi J, Hoeijmakers J, van Steeg H, Vijg J. Aging and genome maintenance: lessons from the mouse?.  Science. 2003;  299 (5611) 1355-1359
    CrossrefPubMedGoogle Scholar
  • 56 Hasty P, Vijg J. Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity.  Aging Cell. 2004;  3 (2) 55-65
    CrossrefPubMedGoogle Scholar
  • 57 Schumacher B, Hoeijmakers J H, Garinis G A. Sealing the gap between nuclear DNA damage and longevity.  Mol Cell Endocrinol. 2009;  299 (1) 112-117
    CrossrefPubMedGoogle Scholar
  • 58 Fowden A L, Forhead A J. Endocrine mechanisms of intrauterine programming.  Reproduction. 2004;  127 (5) 515-526
    CrossrefPubMedGoogle Scholar
  • 59 Fernandez-Capetillo O. Intrauterine programming of ageing.  EMBO Rep. 2010;  11 (1) 32-36
    CrossrefPubMedGoogle Scholar
  • 60 Sinclair D A, Oberdoerffer P. The ageing epigenome: damaged beyond repair?.  Ageing Res Rev. 2009;  8 (3) 189-198
    CrossrefPubMedGoogle Scholar
  • 61 Hales C N, Desai M, Ozanne S E, Crowther N J. Fishing in the stream of diabetes: from measuring insulin to the control of fetal organogenesis.  Biochem Soc Trans. 1996;  24 (2) 341-350
    PubMedGoogle Scholar
  • 62 Heywood W E, Mian N, Milla P J, Lindley K J. Programming of defective rat pancreatic beta-cell function in offspring from mothers fed a low-protein diet during gestation and the suckling periods.  Clin Sci (Lond). 2004;  107 (1) 37-45
    CrossrefPubMedGoogle Scholar
  • 63 Flouris A D, Spiropoulos Y, Sakellariou G J, Koutedakis Y. Effect of seasonal programming on fetal development and longevity: links with environmental temperature.  Am J Hum Biol. 2009;  21 (2) 214-216
    CrossrefPubMedGoogle Scholar
  • 64 Vaiserman A M, Collinson A C, Koshel N M, Belaja I I, Voitenko V P. Seasonal programming of adult longevity in Ukraine.  Int J Biometeorol. 2002;  47 (1) 49-52
    CrossrefPubMedGoogle Scholar
  • 65 Watson P E, McDonald B W. Seasonal variation of nutrient intake in pregnancy: effects on infant measures and possible influence on diseases related to season of birth.  Eur J Clin Nutr. 2007;  61 (11) 1271-1280
    CrossrefPubMedGoogle Scholar
  • 66 Simons J W. Epigenetic hereditary transcription profiles II, aging revisited.  Biol Direct. 2007;  2 39
    CrossrefPubMedGoogle Scholar
  • 67 Thompson R F, Einstein F H. Epigenetic basis for fetal origins of age-related disease.  J Womens Health (Larchmt). 2010;  19 (3) 581-587
    CrossrefPubMedGoogle Scholar
  • 68 Rossi D J, Jamieson C H, Weissman I L. Stems cells and the pathways to aging and cancer.  Cell. 2008;  132 (4) 681-696
    CrossrefPubMedGoogle Scholar
  • 69 Rossi D J, Bryder D, Seita J, Nussenzweig A, Hoeijmakers J, Weissman I L. Deficiencies in DNA damage repair limit the function of haematopoietic stem cells with age.  Nature. 2007;  447 (7145) 725-729
    CrossrefPubMedGoogle Scholar
  • 70 Xu Y, Williams S J, O'Brien D, Davidge S T. Hypoxia or nutrient restriction during pregnancy in rats leads to progressive cardiac remodeling and impairs postischemic recovery in adult male offspring.  FASEB J. 2006;  20 (8) 1251-1253
    CrossrefPubMedGoogle Scholar
  • 71 von Bergen N H, Koppenhafer S L, Spitz D R et al.. Fetal programming alters reactive oxygen species production in sheep cardiac mitochondria.  Clin Sci (Lond). 2009;  116 (8) 659-668
    CrossrefPubMedGoogle Scholar
  • 72 Brouilette S, Singh R K, Thompson J R, Goodall A H, Samani N J. White cell telomere length and risk of premature myocardial infarction.  Arterioscler Thromb Vasc Biol. 2003;  23 (5) 842-846
    CrossrefPubMedGoogle Scholar
  • 73 Akkad A, Hastings R, Konje J C, Bell S C, Thurston H, Williams B. Telomere length in small-for-gestational-age babies.  BJOG. 2006;  113 (3) 318-323
    PubMedGoogle Scholar
  • 74 van Meer H, van Straten E M, Baller J F et al.. The effects of intrauterine malnutrition on maternal-fetal cholesterol transport and fetal lipid synthesis in mice.  Pediatr Res. 2010;  68 (1) 10-15
    CrossrefPubMedGoogle Scholar
  • 75 Burdge G C, Hanson M A, Slater-Jefferies J L, Lillycrop K A. Epigenetic regulation of transcription: a mechanism for inducing variations in phenotype (fetal programming) by differences in nutrition during early life?.  Br J Nutr. 2007;  97 (6) 1036-1046
    CrossrefPubMedGoogle Scholar
  • 76 Delage B, Dashwood R H. Dietary manipulation of histone structure and function.  Annu Rev Nutr. 2008;  28 347-366
    CrossrefPubMedGoogle Scholar
  • 77 El-Osta A, Wolffe A P. DNA methylation and histone deacetylation in the control of gene expression: basic biochemistry to human development and disease.  Gene Expr. 2000;  9 (1-2) 63-75
    PubMedGoogle Scholar
  • 78 Mather K. Genotype X environment interactions. II. Some genetical considerations.  Heredity. 1975;  35 (1) 31-53
    CrossrefPubMedGoogle Scholar
  • 79 Khoury M J, Davis R, Gwinn M, Lindegren M L, Yoon P. Do we need genomic research for the prevention of common diseases with environmental causes?.  Am J Epidemiol. 2005;  161 (9) 799-805
    CrossrefPubMedGoogle Scholar
  • 80 Pérusse L, Bouchard C. Genotype-environment interaction in human obesity.  Nutr Rev. 1999;  57 (5 Pt 2) S31-S37; discussion S37–S38
    PubMedGoogle Scholar
  • 81 Jaffee S R, Price T S. Gene-environment correlations: a review of the evidence and implications for prevention of mental illness.  Mol Psychiatry. 2007;  12 (5) 432-442
    PubMedGoogle Scholar
  • 82 Eaves L J, Sullivan P. Genotype-environment interaction in transmission disequilibrium tests.  Adv Genet. 2001;  42 223-240
    CrossrefPubMedGoogle Scholar
  • 83 Fry J D. Genotype-environment interaction for total fitness in Drosophila.  J Genet. 2008;  87 (4) 355-362
    CrossrefPubMedGoogle Scholar
  • 84 Osmond C, Barker D J. Fetal, infant, and childhood growth are predictors of coronary heart disease, diabetes, and hypertension in adult men and women.  Environ Health Perspect. 2000;  108 (Suppl 3) 545-553
    PubMedGoogle Scholar
  • 85 Diamond J. Pearl Harbor and the emperor's physiologists.  Nat Hist. 1991;  (12) 2-7
    PubMedGoogle Scholar
  • 86 Cooper R L, Kavlock R J. Endocrine disruptors and reproductive development: a weight-of-evidence overview.  J Endocrinol. 1997;  152 (2) 159-166
    CrossrefPubMedGoogle Scholar
  • 87 Ashby J, Houthoff E, Kennedy S J et al.. The challenge posed by endocrine-disrupting chemicals.  Environ Health Perspect. 1997;  105 (2) 164-169
    CrossrefPubMedGoogle Scholar
  • 88 Sumpter J P. Xenoendorine disrupters—environmental impacts.  Toxicol Lett. 1998;  102–103 337-342
    PubMedGoogle Scholar
  • 89 Baptista T. Body weight gain induced by antipsychotic drugs: mechanisms and management.  Acta Psychiatr Scand. 1999;  100 (1) 3-16
    CrossrefPubMedGoogle Scholar
  • 90 Barker D J, Bergmann R L, Ogra P L. Concluding remarks. The window of opportunity: pre-pregnancy to 24 months of age.  Nestle Nutr Workshop Ser Pediatr Program. 2008;  61 255-260
    PubMedGoogle Scholar
  • 91 Lartey A. Maternal and child nutrition in sub-Saharan Africa: challenges and interventions.  Proc Nutr Soc. 2008;  67 (1) 105-108
    CrossrefPubMedGoogle Scholar
  • 92 Cameron N, Demerath E W. Critical periods in human growth and their relationship to diseases of aging.  Am J Phys Anthropol. 2002;  35 (Suppl 35) 159-184
    PubMedGoogle Scholar
  • 93 Dodic M, May C N, Wintour E M, Coghlan J P. An early prenatal exposure to excess glucocorticoid leads to hypertensive offspring in sheep.  Clin Sci (Lond). 1998;  94 (2) 149-155
    PubMedGoogle Scholar
  • 94 Moritz K M, Jefferies A, Wintour E M, Dodic M. Fetal renal and blood pressure responses to steroid infusion after early prenatal treatment with dexamethasone.  Am J Physiol Regul Integr Comp Physiol. 2005;  288 (1) R62-R66
    PubMedGoogle Scholar
  • 95 Painter R C, Roseboom T J, Bleker O P. Prenatal exposure to the Dutch famine and disease in later life: an overview.  Reprod Toxicol. 2005;  20 (3) 345-352
    CrossrefPubMedGoogle Scholar
  • 96 Brown S B, Libonati J R, Selak M A, Shannon R P, Simmons R A. Neonatal exendin-4 leads to protection from reperfusion injury and reduced rates of oxidative phosphorylation in the adult rat heart.  Cardiovasc Drugs Ther. 2010;  24 (3) 197-205
    CrossrefPubMedGoogle Scholar
  • 97 Ham J N, Crutchlow M F, Desai B M, Simmons R A, Stoffers D A. Exendin-4 normalizes islet vascularity in intrauterine growth restricted rats: potential role of VEGF.  Pediatr Res. 2009;  66 (1) 42-46
    CrossrefPubMedGoogle Scholar
  • 98 Raab E L, Vuguin P M, Stoffers D A, Simmons R A. Neonatal exendin-4 treatment reduces oxidative stress and prevents hepatic insulin resistance in intrauterine growth-retarded rats.  Am J Physiol Regul Integr Comp Physiol. 2009;  297 (6) R1785-R1794
    CrossrefPubMedGoogle Scholar
  • 99 Stoffers D A, Desai B M, DeLeon D D, Simmons R A. Neonatal exendin-4 prevents the development of diabetes in the intrauterine growth retarded rat.  Diabetes. 2003;  52 (3) 734-740
    CrossrefPubMedGoogle Scholar
  • 100 Dötsch J, Plank C, Amann K, Ingelfinger J. The implications of fetal programming of glomerular number and renal function.  J Mol Med. 2009;  87 (9) 841-848
    CrossrefPubMedGoogle Scholar
  • 101 Engelbregt M J, Houdijk M E, Popp-Snijders C, Delemarre-van de Waal H A. The effects of intra-uterine growth retardation and postnatal undernutrition on onset of puberty in male and female rats.  Pediatr Res. 2000;  48 (6) 803-807
    CrossrefPubMedGoogle Scholar
  • 102 Jaquet D, Leger J, Chevenne D, Czernichow P, Levy-Marchal C. Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women.  J Clin Endocrinol Metab. 1999;  84 (11) 3945-3949
    CrossrefPubMedGoogle Scholar
  • 103 Morrison J L, Duffield J A, Muhlhausler B S, Gentili S, McMillen I C. Fetal growth restriction, catch-up growth and the early origins of insulin resistance and visceral obesity.  Pediatr Nephrol. 2010;  25 (4) 669-677
    CrossrefPubMedGoogle Scholar
  • 104 Twins confirm importance of fetal programming on adult blood pressure.  BMJ. 1999;  319 (7221) C
    PubMedGoogle Scholar
  • 105 Cheung Y F, Taylor M J, Fisk N M, Redington A N, Gardiner H M. Fetal origins of reduced arterial distensibility in the donor twin in twin-twin transfusion syndrome.  Lancet. 2000;  355 (9210) 1157-1158
    CrossrefPubMedGoogle Scholar
  • 106 Bebbington M. Twin-to-twin transfusion syndrome: current understanding of pathophysiology, in-utero therapy and impact for future development.  Semin Fetal Neonatal Med. 2010;  15 (1) 15-20
    CrossrefPubMedGoogle Scholar
  • 107 Liu C, Zhang L F, Song M L, Bao H G, Zhao C J, Li N. Highly efficient dissociation of oxygen from hemoglobin in Tibetan chicken embryos compared with lowland chicken embryos incubated in hypoxia.  Poult Sci. 2009;  88 (12) 2689-2694
    CrossrefPubMedGoogle Scholar
  • 108 Tintu A, Rouwet E, Verlohren S et al.. Hypoxia induces dilated cardiomyopathy in the chick embryo: mechanism, intervention, and long-term consequences.  PLoS ONE. 2009;  4 (4) e5155
    CrossrefPubMedGoogle Scholar
  • 109 Giussani D A, Salinas C E, Villena M, Blanco C E. The role of oxygen in prenatal growth: studies in the chick embryo.  J Physiol. 2007;  585 (Pt 3) 911-917
    CrossrefPubMedGoogle Scholar
  • 110 Barry J S, Rozance P J, Anthony R V. An animal model of placental insufficiency-induced intrauterine growth restriction.  Semin Perinatol. 2008;  32 (3) 225-230
    CrossrefPubMedGoogle Scholar
  • 111 Matsumoto H, Fukui E, Yoshizawa M. Differential Interactions between embryo and uterus during implantation in laboratory animals.  J Mamm Ova Res. 2009;  26 111-115
    CrossrefPubMedGoogle Scholar
  • 112 Carter A M, Enders A C, Jones C J et al.. Comparative placentation and animal models: patterns of trophoblast invasion—a workshop report.  Placenta. 2006;  27 (Suppl A) S30-S33
    CrossrefPubMedGoogle Scholar
  • 113 Mess A. The Guinea pig placenta: model of placental growth dynamics.  Placenta. 2007;  28 (8–9) 812-815
    CrossrefPubMedGoogle Scholar
  • 114 Roselli C E, Stormshak F. Prenatal programming of sexual partner preference: the ram model.  J Neuroendocrinol. 2009;  21 (4) 359-364
    CrossrefPubMedGoogle Scholar
  • 115 Giussani D A, Riquelme R A, Sanhueza E M, Hanson M A, Blanco C E, Llanos A J. Adrenergic and vasopressinergic contributions to the cardiovascular response to acute hypoxaemia in the llama fetus.  J Physiol. 1999;  515 (Pt 1) 233-241
    CrossrefPubMedGoogle Scholar
  • 116 Anthony R V, Scheaffer A N, Wright C D, Regnault T R. Ruminant models of prenatal growth restriction.  Reprod Suppl. 2003;  61 183-194
    PubMedGoogle Scholar
  • 117 Farley D, Tejero M E, Comuzzie A G et al.. Feto-placental adaptations to maternal obesity in the baboon.  Placenta. 2009;  30 (9) 752-760
    CrossrefPubMedGoogle Scholar
  • 118 Aida K, Wang X L, Wang J, Li C, McDonald T J, Nathanielsz P W. Effect of betamethasone administration to the pregnant baboon at 0.75 gestation on placental eNOS distribution and activity.  Placenta. 2004;  25 (10) 780-787
    CrossrefPubMedGoogle Scholar
  • 119 Morrison J L. Sheep models of intrauterine growth restriction: fetal adaptations and consequences.  Clin Exp Pharmacol Physiol. 2008;  35 (7) 730-743
    CrossrefPubMedGoogle Scholar
  • 120 Godfrey K M, Forrester T, Barker D J et al.. Maternal nutritional status in pregnancy and blood pressure in childhood.  Br J Obstet Gynaecol. 1994;  101 (5) 398-403
    CrossrefPubMedGoogle Scholar
  • 121 Latini G, De Mitri B, Del Vecchio A, Chitano G, De Felice C, Zetterström R. Foetal growth of kidneys, liver and spleen in intrauterine growth restriction: “programming” causing “metabolic syndrome” in adult age.  Acta Paediatr. 2004;  93 (12) 1635-1639
    CrossrefPubMedGoogle Scholar
  • 122 McArdle H J, Andersen H S, Jones H, Gambling L. Fetal programming: causes and consequences as revealed by studies of dietary manipulation in rats—a review.  Placenta. 2006;  27 (Suppl A) S56-S60
    PubMedGoogle Scholar
  • 123 Williams S J, Hemmings D G, Mitchell J M, McMillen I C, Davidge S T. Effects of maternal hypoxia or nutrient restriction during pregnancy on endothelial function in adult male rat offspring.  J Physiol. 2005;  565 (Pt 1) 125-135
    CrossrefPubMedGoogle Scholar
  • 124 Gilbert J S, Babcock S A, Granger J P. Hypertension produced by reduced uterine perfusion in pregnant rats is associated with increased soluble fms-like tyrosine kinase-1 expression.  Hypertension. 2007;  50 (6) 1142-1147
    CrossrefPubMedGoogle Scholar
  • 125 Cheung C Y, Bogic L, Gagnon R, Harding R, Brace R A. Morphologic alterations in ovine placenta and fetal liver following induced severe placental insufficiency.  J Soc Gynecol Investig. 2004;  11 (8) 521-528
    CrossrefPubMedGoogle Scholar
  • 126 Giles W B, Trudinger B J, Stevens D, Alexander G, Bradley L. Umbilical artery flow velocity waveform analysis in normal ovine pregnancy and after carunculectomy.  J Dev Physiol. 1989;  11 (3) 135-138
    PubMedGoogle Scholar
  • 127 Andersson I J, Jiang Y Y, Davidge S T. Maternal stress and development of atherosclerosis in the adult apolipoprotein E-deficient mouse offspring.  Am J Physiol Regul Integr Comp Physiol. 2009;  296 (3) R663-R671
    PubMedGoogle Scholar
  • 128 Shankar K, Harrell A, Liu X, Gilchrist J M, Ronis M J, Badger T M. Maternal obesity at conception programs obesity in the offspring.  Am J Physiol Regul Integr Comp Physiol. 2008;  294 (2) R528-R538
    PubMedGoogle Scholar
  • 129 Reynolds R M. Corticosteroid-mediated programming and the pathogenesis of obesity and diabetes.  J Steroid Biochem Mol Biol. 2010;  122 (1–3) 3-9
    CrossrefPubMedGoogle Scholar
  • 130 de Souza MdaS, Lima P H, Sinzato Y K, Rudge M V, Pereira O C, Damasceno D C. Effects of cigarette smoke exposure on pregnancy outcome and offspring of diabetic rats.  Reprod Biomed Online. 2009;  18 (4) 562-567
    CrossrefPubMedGoogle Scholar
  • 131 Feng Y, Caiping M, Li C et al.. Fetal and offspring arrhythmia following exposure to nicotine during pregnancy.  J Appl Toxicol. 2010;  30 (1) 53-58
    CrossrefPubMedGoogle Scholar
  • 132 Morton J S, Rueda-Clausen C F, Davidge S T. Mechanisms of endothelium-dependent vasodilation in male and female, young and aged offspring born growth restricted.  Am J Physiol Regul Integr Comp Physiol. 2010;  298 (4) R930-R938
    CrossrefPubMedGoogle Scholar
  • 133 Hemmings D G, Williams S J, Davidge S T. Increased myogenic tone in 7-month-old adult male but not female offspring from rat dams exposed to hypoxia during pregnancy.  Am J Physiol Heart Circ Physiol. 2005;  289 (2) H674-H682
    CrossrefPubMedGoogle Scholar
  • 134 Williams S J, Campbell M E, McMillen I C, Davidge S T. Differential effects of maternal hypoxia or nutrient restriction on carotid and femoral vascular function in neonatal rats.  Am J Physiol Regul Integr Comp Physiol. 2005;  288 (2) R360-R367
    PubMedGoogle Scholar
  • 135 Rueda-Clausen C F, Morton J S, Davidge S T. Effects of hypoxia-induced intrauterine growth restriction on cardiopulmonary structure and function during adulthood.  Cardiovasc Res. 2009;  81 (4) 713-722
    PubMedGoogle Scholar
  • 136 Xue Q, Zhang L. Prenatal hypoxia causes a sex-dependent increase in heart susceptibility to ischemia and reperfusion injury in adult male offspring: role of protein kinase C epsilon.  J Pharmacol Exp Ther. 2009;  330 (2) 624-632
    CrossrefPubMedGoogle Scholar
  • 137 Zhang L. Prenatal hypoxia and cardiac programming.  J Soc Gynecol Investig. 2005;  12 (1) 2-13
    PubMedGoogle Scholar
  • 138 Marsál K. Intrauterine growth restriction.  Curr Opin Obstet Gynecol. 2002;  14 (2) 127-135
    CrossrefPubMedGoogle Scholar
  • 139 Jobgen W S, Ford S P, Jobgen S C et al.. Baggs ewes adapt to maternal undernutrition and maintain conceptus growth by maintaining fetal plasma concentrations of amino acids.  J Anim Sci. 2008;  86 (4) 820-826
    CrossrefPubMedGoogle Scholar
  • 140 Cogswell M E, Yip R. The influence of fetal and maternal factors on the distribution of birthweight.  Semin Perinatol. 1995;  19 (3) 222-240
    CrossrefPubMedGoogle Scholar
  • 141 Hickey R J, Clelland R C, Bowers E J. Maternal smoking, birth weight, infant death, and the self-selection problem.  Am J Obstet Gynecol. 1978;  131 (7) 805-811
    PubMedGoogle Scholar
  • 142 Gale C R, Martyn C N. Birth weight and later risk of depression in a national birth cohort.  Br J Psychiatry. 2004;  184 28-33
    CrossrefPubMedGoogle Scholar
  • 143 Jones A, Godfrey K M, Wood P, Osmond C, Goulden P, Phillips D I. Fetal growth and the adrenocortical response to psychological stress.  J Clin Endocrinol Metab. 2006;  91 (5) 1868-1871
    CrossrefPubMedGoogle Scholar
  • 144 Kranendonk G, Mulder E J, Parvizi N, Taverne M A. Prenatal stress in pigs: experimental approaches and field observations.  Exp Clin Endocrinol Diabetes. 2008;  116 (7) 413-422
    Article in Thieme ConnectPubMedGoogle Scholar
  • 145 Gore A C. Developmental programming and endocrine disruptor effects on reproductive neuroendocrine systems.  Front Neuroendocrinol. 2008;  29 (3) 358-374
    CrossrefPubMedGoogle Scholar
  • 146 Nuyt A M, Alexander B T. Developmental programming and hypertension.  Curr Opin Nephrol Hypertens. 2009;  18 (2) 144-152
    CrossrefPubMedGoogle Scholar
  • 147 Plagemann A. A matter of insulin: developmental programming of body weight regulation.  J Matern Fetal Neonatal Med. 2008;  21 (3) 143-148
    CrossrefPubMedGoogle Scholar
  • 148 Chechi K, McGuire J J, Cheema S K. Developmental programming of lipid metabolism and aortic vascular function in C57BL/6 mice: a novel study suggesting an involvement of LDL-receptor.  Am J Physiol Regul Integr Comp Physiol. 2009;  296 (4) R1029-R1040
    CrossrefPubMedGoogle Scholar
  • 149 Prior L J, Armitage J A. Neonatal overfeeding leads to developmental programming of adult obesity: you are what you ate.  J Physiol. 2009;  587 (Pt 11) 2419
    CrossrefPubMedGoogle Scholar
  • 150 Lampl M, Jeanty P. Timing is everything: a reconsideration of fetal growth velocity patterns identifies the importance of individual and sex differences.  Am J Hum Biol. 2003;  15 (5) 667-680
    CrossrefPubMedGoogle Scholar
  • 151 O'Regan D, Kenyon C J, Seckl J R, Holmes M C. Glucocorticoid exposure in late gestation in the rat permanently programs gender-specific differences in adult cardiovascular and metabolic physiology.  Am J Physiol Endocrinol Metab. 2004;  287 (5) E863-E870
    CrossrefPubMedGoogle Scholar
  • 152 Mueller B R, Bale T L. Sex-specific programming of offspring emotionality after stress early in pregnancy.  J Neurosci. 2008;  28 (36) 9055-9065
    CrossrefPubMedGoogle Scholar
  • 153 Khan I Y, Taylor P D, Dekou V et al.. Gender-linked hypertension in offspring of lard-fed pregnant rats.  Hypertension. 2003;  41 (1) 168-175
    CrossrefPubMedGoogle Scholar
  • 154 McArthur S, Siddique Z L, Christian H C et al.. Perinatal glucocorticoid treatment disrupts the hypothalamo-lactotroph axis in adult female, but not male, rats.  Endocrinology. 2006;  147 (4) 1904-1915
    PubMedGoogle Scholar
  • 155 Ojeda N B, Grigore D, Yanes L L et al.. Testosterone contributes to marked elevations in mean arterial pressure in adult male intrauterine growth restricted offspring.  Am J Physiol Regul Integr Comp Physiol. 2007;  292 (2) R758-R763
    PubMedGoogle Scholar
  • 156 Ojeda N B, Grigore D, Robertson E B, Alexander B T. Estrogen protects against increased blood pressure in postpubertal female growth restricted offspring.  Hypertension. 2007;  50 (4) 679-685
    CrossrefPubMedGoogle Scholar
  • 157 Langley-Evans S C, Jackson A A. Captopril normalises systolic blood pressure in rats with hypertension induced by fetal exposure to maternal low protein diets.  Comp Biochem Physiol Physiol. 1995;  110 (3) 223-228
    CrossrefPubMedGoogle Scholar
  • 158 Rich-Edwards J W, Stampfer M J, Manson J E et al.. Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976.  BMJ. 1997;  315 (7105) 396-400
    CrossrefPubMedGoogle Scholar
  • 159 Chamson-Reig A, Thyssen S M, Hill D J, Arany E. Exposure of the pregnant rat to low protein diet causes impaired glucose homeostasis in the young adult offspring by different mechanisms in males and females.  Exp Biol Med (Maywood). 2009;  234 (12) 1425-1436
    CrossrefPubMedGoogle Scholar
  • 160 Weinberg J, Sliwowska J H, Lan N, Hellemans K G. Prenatal alcohol exposure: foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome.  J Neuroendocrinol. 2008;  20 (4) 470-488
    CrossrefPubMedGoogle Scholar

Sandra T DavidgePh.D. 

220 HMRC, University of Alberta

Edmonton, AB, Canada T6G 2S2

Email: sandra.davidge@ualberta.ca

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