Skip to main content

Advertisement

SpringerLink
Log in

Intergenerational programming of metabolic disease: evidence from human populations and experimental animal models

  • Multi-author review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

We are in the midst of unparalleled epidemics of obesity and type 2 diabetes—complex phenotypes originating at the intersection of genetic and environmental risk. As detailed in other chapters, evidence indicates that non-genetic, or environmental, risk may initiate during prenatal and early postnatal life [1]. Striking examples in humans include the association of low birth weight (LBW) and/or accelerated early growth with increased risk of insulin resistance, obesity, type 2 diabetes (T2DM), and cardiovascular disease (CVD), and the close relationship between maternal obesity or diabetes with childhood obesity. In this chapter, we will focus on the intriguing emerging data from both human and animal models that indicate that intrauterine and childhood exposures can also influence risk for diabetes and cardiovascular disease in subsequent generations. Understanding the mechanisms responsible for these effects is critical in order to develop effective metabolic and nutritional interventions to interrupt such vicious intergenerational cycles potentiating risk for metabolic disorders.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Gluckman PD, Hanson MA, Cooper C, Thornburg KL (2008) Effect of in utero and early-life conditions on adult health and disease. N Engl J Med 359:61–73

    Article  PubMed  CAS  Google Scholar 

  2. Plagemann A, Heidrich I, Gotz F, Rohde W, Dorner G (1992) Lifelong enhanced diabetes susceptibility and obesity after temporary intrahypothalamic hyperinsulinism during brain organization. Exp Clin Endocrinol 99:91–95

    Article  PubMed  CAS  Google Scholar 

  3. Schaefer-Graf UM, Graf K, Kulbacka I et al (2008) Maternal lipids as strong determinants of fetal environment and growth in pregnancies with gestational diabetes mellitus. Diabetes Care 31:1858–1863

    Article  PubMed  Google Scholar 

  4. Persson B, Westgren M, Celsi G, Nord E, Ortqvist E (1999) Leptin concentrations in cord blood in normal newborn infants and offspring of diabetic mothers. Horm Metab Res 31:467–471

    Article  PubMed  CAS  Google Scholar 

  5. McMillen IC, Edwards LJ, Duffield J, Muhlhausler BS (2006) Regulation of leptin synthesis and secretion before birth: implications for the early programming of adult obesity. Reproduction 131:415–427

    Article  PubMed  CAS  Google Scholar 

  6. Henstridge DC, Drew BG, Formosa MF et al (2009) The effect of the nitric oxide donor sodium nitroprusside on glucose uptake in human primary skeletal muscle cells. Nitric Oxide 21:126–131

    Article  PubMed  CAS  Google Scholar 

  7. Rodriguez-Martinez H, Kvist U, Ernerudh J, Sanz L, Calvete JJ (2011) Seminal plasma proteins: what role do they play? Am J Reprod Immunol 66(Suppl 1):11–22

    Article  PubMed  Google Scholar 

  8. Ram KR, Wolfner MF (2009) A network of interactions among seminal proteins underlies the long-term postmating response in Drosophila. Proc Natl Acad Sci USA 106:15384–15389

    Article  PubMed  CAS  Google Scholar 

  9. Emami N, Diamandis EP (2010) Potential role of multiple members of the kallikrein-related peptidase family of serine proteases in activating latent TGF beta 1 in semen. Biol. Chem 391:85–95

    Article  PubMed  CAS  Google Scholar 

  10. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ (1989) Weight in infancy and death from ischaemic heart disease. Lancet 2:577–580

    Article  PubMed  CAS  Google Scholar 

  11. Hales CN, Barker DJ, Clark PM et al (1991) Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 303:1019–1022

    Article  PubMed  CAS  Google Scholar 

  12. Oken E, Gillman MW (2003) Fetal origins of obesity. Obes Res 11:496–506

    Article  PubMed  Google Scholar 

  13. Gluckman PD, Hanson MA, Beedle AS (2007) Non-genomic transgenerational inheritance of disease risk. BioEssays 29:145–154

    Article  PubMed  CAS  Google Scholar 

  14. Veena SR, Geetha S, Leary SD et al (2007) Relationships of maternal and paternal birthweights to features of the metabolic syndrome in adult offspring: an inter-generational study in South India. Diabetologia 50:43–54

    Article  PubMed  CAS  Google Scholar 

  15. Dabelea D, Pettitt DJ (2001) Intrauterine diabetic environment confers risks for type 2 diabetes mellitus and obesity in the offspring, in addition to genetic susceptibility. J Pediatr Endocrinol Metab 14:1085–1091

    PubMed  CAS  Google Scholar 

  16. Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA (2003) Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics 111:e221–e226

    Article  PubMed  Google Scholar 

  17. Crume TL, Ogden L, Daniels S, Hamman RF, Norris JM, Dabelea D (2011) The impact of in utero exposure to diabetes on childhood body mass index growth trajectories: the EPOCH study. J Pediatr 158:941–946

    Article  PubMed  Google Scholar 

  18. Dabelea D, Hanson RL, Lindsay RS et al (2000) Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes 49:2208–2211

    Article  PubMed  CAS  Google Scholar 

  19. Lawlor DA, Lichtenstein P, Langstrom N (2011) Association of maternal diabetes mellitus in pregnancy with offspring adiposity into early adulthood: sibling study in a prospective cohort of 280,866 men from 248,293 families. Circulation 123:258–265

    Article  PubMed  Google Scholar 

  20. Dabelea D, Crume T (2011) Maternal environment and the transgenerational cycle of obesity and diabetes. Diabetes 60:1849–1855

    Article  PubMed  CAS  Google Scholar 

  21. Reynolds RM, Osmond C, Phillips DI, Godfrey KM (2010) Maternal BMI, parity, and pregnancy weight gain: influences on offspring adiposity in young adulthood. J Clin Endocrinol Metab 95:5365–5369

    Article  PubMed  CAS  Google Scholar 

  22. Petitt DJ, Bennett PH, Knowler WC, Baird HR, Aleck KA (1985) Gestational diabetes mellitus and impaired glucose tolerance during pregnancy. Long-term effects on obesity and glucose tolerance in the offspring. Diabetes 34(Suppl 2):119–122

    PubMed  Google Scholar 

  23. Kral JG, Biron S, Simard S et al (2006) Large maternal weight loss from obesity surgery prevents transmission of obesity to children who were followed for 2 to 18 years. Pediatrics 118:e1644–e1649

    Article  PubMed  Google Scholar 

  24. Pembrey ME (2010) Male-line transgenerational responses in humans. Hum Fertil (Camb) 13:268–271

    Article  Google Scholar 

  25. Stein AD, Kahn HS, Rundle A, Zybert PA (2007) van der Pal-de Bruin, Lumey LH. Anthropometric measures in middle age after exposure to famine during gestation: evidence from the Dutch famine. Am J Clin Nutr 85:869–876

    PubMed  CAS  Google Scholar 

  26. Painter RC, Osmond C, Gluckman P, Hanson M, Phillips DI, Roseboom TJ (2008) Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG 115:1243–1249

    Article  PubMed  CAS  Google Scholar 

  27. Lumey LH (1992) Decreased birthweights in infants after maternal in utero exposure to the Dutch famine of 1944–1945. Paediatr Perinat Epidemiol 6:240–253

    Article  PubMed  CAS  Google Scholar 

  28. Lumey LH, Stein AD, Ravelli AC (1995) Timing of prenatal starvation in women and offspring birth weight: an update. Eur.J Obstet Gynecol Reprod Biol 63:197

    Article  PubMed  CAS  Google Scholar 

  29. Veena SR, Kumaran K, Swarnagowri MN et al (2004) Intergenerational effects on size at birth in South India. Paediatr Perinat Epidemiol 18:361–370

    Article  PubMed  CAS  Google Scholar 

  30. Ahlsson F, Gustafsson J, Tuvemo T, Lundgren M (2007) Females born large for gestational age have a doubled risk of giving birth to large for gestational age infants. Acta Paediatr 96:358–362

    Article  PubMed  CAS  Google Scholar 

  31. Stein AD, Barnhart HX, Wang M et al (2004) Comparison of linear growth patterns in the first 3 years of life across two generations in Guatemala. Pediatrics 113:e270–e275

    Article  PubMed  Google Scholar 

  32. Li L, Law C, Lo CR, Power C (2009) Intergenerational influences on childhood body mass index: the effect of parental body mass index trajectories. Am J Clin Nutr 89:551–557

    Article  PubMed  CAS  Google Scholar 

  33. Bygren LO, Kaati G, Edvinsson S (2001) Longevity determined by paternal ancestors’ nutrition during their slow growth period. Acta Biotheor 49:53–59

    Article  PubMed  CAS  Google Scholar 

  34. Kaati G, Bygren LO, Edvinsson S (2002) Cardiovascular and diabetes mortality determined by nutrition during parents’ and grandparents’ slow growth period. Eur J Hum Genet 10:682–688

    Article  PubMed  CAS  Google Scholar 

  35. Kaati G, Bygren LO, Pembrey M, Sjostrom M (2007) Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet 15:784–790

    Article  PubMed  CAS  Google Scholar 

  36. Pembrey ME, Bygren LO, Kaati G et al (2006) Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet 14:159–166

    Article  PubMed  Google Scholar 

  37. Davis MM, McGonagle K, Schoeni RF, Stafford F (2008) Grandparental and parental obesity influences on childhood overweight: implications for primary care practice. J Am Board Fam. Med 21:549–554

    Article  PubMed  Google Scholar 

  38. Zambrano E, Martinez-Samayoa PM, Bautista CJ et al (2005) Sex differences in transgenerational alterations of growth and metabolism in progeny (F2) of female offspring (F1) of rats fed a low protein diet during pregnancy and lactation. J Physiol 566:225–236

    Article  PubMed  CAS  Google Scholar 

  39. Crescenzo R, Lionetti L, Mollica MP et al (2006) Altered skeletal muscle subsarcolemmal mitochondrial compartment during catch-up fat after caloric restriction. Diabetes 55:2286–2293

    Article  PubMed  CAS  Google Scholar 

  40. Drake AJ, Walker BR, Seckl JR (2005) Intergenerational consequences of fetal programming by in utero exposure to glucocorticoids in rats. Am J Physiol. Regul Integr Comp Physiol 288:R34–R38

    Article  CAS  Google Scholar 

  41. Burdge GC, Slater-Jefferies J, Torrens C, Phillips ES, Hanson MA, Lillycrop KA (2007) Dietary protein restriction of pregnant rats in the F0 generation induces altered methylation of hepatic gene promoters in the adult male offspring in the F1 and F2 generations. Br J Nutr 97:435–439

    Article  PubMed  CAS  Google Scholar 

  42. Anderson LM, Riffle L, Wilson R, Travlos GS, Lubomirski MS, Alvord WG (2006) Preconceptional fasting of fathers alters serum glucose in offspring of mice. Nutrition 22:327–331

    Article  PubMed  CAS  Google Scholar 

  43. Jimenez-Chillaron JC, Isganaitis E, Charalambous M et al (2009) Intergenerational transmission of glucose intolerance and obesity by in utero undernutrition in mice. Diabetes 58:460–468

    Article  PubMed  CAS  Google Scholar 

  44. Carone BR, Fauquier L, Habib N et al (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084–1096

    Article  PubMed  CAS  Google Scholar 

  45. Ng SF, Lin RC, Laybutt DR, Barres R, Owens JA, Morris MJ (2010) Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467:963–966

    Article  PubMed  CAS  Google Scholar 

  46. Daxinger L, Whitelaw E (2012) Understanding transgenerational epigenetic inheritance via the gametes in mammals. Nat Rev Genet 13:153–162

    Article  PubMed  CAS  Google Scholar 

  47. Sutherland HG, Kearns M, Morgan HD et al (2000) Reactivation of heritably silenced gene expression in mice. Mamm Genome 11:347–355

    Article  PubMed  CAS  Google Scholar 

  48. Morgan HD, Sutherland HG, Martin DI, Whitelaw E (1999) Epigenetic inheritance at the agouti locus in the mouse. Nat Genet 23:314–318

    Article  PubMed  CAS  Google Scholar 

  49. Blewitt ME, Vickaryous NK, Paldi A, Koseki H, Whitelaw E (2006) Dynamic reprogramming of DNA methylation at an epigenetically sensitive allele in mice. PLoS Genet 2:e49

    Article  PubMed  CAS  Google Scholar 

  50. Dolinoy DC, Weinhouse C, Jones TR, Rozek LS, Jirtle RL (2010) Variable histone modifications at the A(vy) metastable epiallele. Epigenetics 5:637–644

    Article  PubMed  CAS  Google Scholar 

  51. Cropley JE, Suter CM, Beckman KB, Martin DI (2006) Germ-line epigenetic modification of the murine A vy allele by nutritional supplementation. Proc Natl Acad Sci USA 103:17308–17312

    Article  PubMed  CAS  Google Scholar 

  52. Waterland RA, Travisano M, Tahiliani KG (2007) Diet-induced hypermethylation at agouti viable yellow is not inherited transgenerationally through the female. FASEB J 21:3380–3385

    Article  PubMed  CAS  Google Scholar 

  53. Waterland RA, Jirtle RL (2003) Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 23:5293–5300

    Article  PubMed  CAS  Google Scholar 

  54. Rakyan VK, Chong S, Champ ME et al (2003) Transgenerational inheritance of epigenetic states at the murine Axin(Fu) allele occurs after maternal and paternal transmission. Proc Natl Acad Sci USA 100:2538–2543

    Article  PubMed  CAS  Google Scholar 

  55. Nelson VR, Spiezio SH, Nadeau JH (2010) Transgenerational genetic effects of the paternal Y chromosome on daughters’ phenotypes. Epigenomics 2:513–521

    Article  PubMed  CAS  Google Scholar 

  56. Nelson VR, Heaney JD, Tesar PJ, Davidson NO, Nadeau JH (2012) Transgenerational epigenetic effects of the Apobec1 cytidine deaminase deficiency on testicular germ cell tumor susceptibility and embryonic viability. Proc Natl Acad Sci USA 109:E2766–E2773

    Article  PubMed  CAS  Google Scholar 

  57. Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F (2006) RNA-mediated non-Mendelian inheritance of an epigenetic change in the mouse. Nature 441:469–474

    Article  PubMed  CAS  Google Scholar 

  58. Yazbek SN, Spiezio SH, Nadeau JH, Buchner DA (2010) Ancestral paternal genotype controls body weight and food intake for multiple generations. Hum Mol Genet 19:4134–4144

    Article  PubMed  CAS  Google Scholar 

  59. Nelson VR, Nadeau JH (2010) Transgenerational genetic effects. Epigenomics 2:797–806

    Article  PubMed  CAS  Google Scholar 

  60. Jimenez-Chillaron JC, Hernandez-Valencia M, Reamer C et al (2005) Beta-cell secretory dysfunction in the pathogenesis of low birth weight-associated diabetes: a murine model. Diabetes 54:702–711

    Article  PubMed  CAS  Google Scholar 

  61. Jimenez-Chillaron JC, Hernandez-Valencia M, Lightner A et al (2006) Reductions in caloric intake and early postnatal growth prevent glucose intolerance and obesity associated with low birthweight. Diabetologia 49:1974–1984

    Article  PubMed  CAS  Google Scholar 

  62. Isganaitis E, Jimenez-Chillaron J, Woo M et al (2009) Accelerated postnatal growth increases lipogenic gene expression and adipocyte size in low-birth weight mice. Diabetes 58:1192–1200

    Article  PubMed  CAS  Google Scholar 

  63. McCurdy CE, Bishop JM, Williams SM et al (2009) Maternal high-fat diet triggers lipotoxicity in the fetal livers of nonhuman primates. J Clin Invest 119:323–335

    PubMed  CAS  Google Scholar 

  64. Isganaitis E, Woo M, Lee K-J, DeCoste J, Fitzpatrick C, Patti ME (2009) In utero exposure to insulin resistance results in accelerated weight gain and hyperinsulinemia in offspring. Diabetes 58(Supplement 1):A85

    Google Scholar 

  65. Carmody JS, Wan P, Accili D, Zeltser LM, Leibel RL (2011) Respective contributions of maternal insulin resistance and diet to metabolic and hypothalamic phenotypes of progeny. Obesity (Silver Spring) 19:492–499

    Article  CAS  Google Scholar 

  66. Bertram C, Khan O, Ohri S, Phillips DI, Matthews SG, Hanson MA (2008) Transgenerational effects of prenatal nutrient restriction on cardiovascular and hypothalamic-pituitary-adrenal function. J Physiol 586:2217–2229

    Article  PubMed  CAS  Google Scholar 

  67. Bellinger L, Sculley DV, Langley-Evans SC (2006) Exposure to undernutrition in fetal life determines fat distribution, locomotor activity and food intake in ageing rats. Int J Obes (Lond) 30:729–738

    Article  CAS  Google Scholar 

  68. Woo M, Isganaitis E, Cerletti M et al (2011) Early Life nutrition modulates muscle stem cell number: implications for muscle mass and repair. Stem Cells Dev 20:1763–1769

    Article  PubMed  CAS  Google Scholar 

  69. Woo M, Patti ME (2008) Diabetes risk begins in utero. Cell Metab 8:5–7

    Article  PubMed  CAS  Google Scholar 

  70. Dunn GA, Bale TL (2011) Maternal high-fat diet effects on third-generation female body size via the paternal lineage. Endocrinology 152:2228–2236

    Article  PubMed  CAS  Google Scholar 

  71. Pentinat T, Ramon-Krauel M, Cebria J, Diaz R, Jimenez-Chillaron JC (2010) Transgenerational inheritance of glucose intolerance in a mouse model of neonatal overnutrition. Endocrinology 151:5617–5623

    Article  PubMed  CAS  Google Scholar 

  72. Anway MD, Cupp AS, Uzumcu M, Skinner MK (2005) Epigenetic transgenerational actions of endocrine disruptors and male fertility. Science 308:1466–1469

    Article  PubMed  CAS  Google Scholar 

  73. Guerrero-Bosagna C, Settles M, Lucker B, Skinner MK (2010) Epigenetic transgenerational actions of vinclozolin on promoter regions of the sperm epigenome. PLoS one 5(9):e13100. doi:10.1371/journal.pone.0013100

  74. Weaver IC, Cervoni N, Champagne FA et al (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854

    Article  PubMed  CAS  Google Scholar 

  75. Ferguson-Smith AC, Patti ME (2011) You are what your dad ate. Cell Metab 13:115–117

    Article  PubMed  CAS  Google Scholar 

  76. Lillycrop KA, Phillips ES, Torrens C, Hanson MA, Jackson AA, Burdge GC (2008) Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring. Br J Nutr 100:278–282

    Article  PubMed  CAS  Google Scholar 

  77. Bakos HW, Mitchell M, Setchell BP, Lane M (2011) The effect of paternal diet-induced obesity on sperm function and fertilization in a mouse model. Int J Androl 34:402–410

    Article  PubMed  CAS  Google Scholar 

  78. Ivanova E, Chen JH, Segonds-Pichon A, Ozanne SE, Kelsey G (2012) DNA methylation at differentially methylated regions of imprinted genes are resistant to developmental programming by maternal nutrition. Epigenetics 7:1200–1210

    Article  PubMed  CAS  Google Scholar 

  79. Radford EJ, Isganaitis E, Jimenez-Chillaron J et al (2012) An unbiased assessment of the role of imprinted genes in an intergenerational model of developmental programming. PLoS Genet 8:e1002605

    Article  PubMed  CAS  Google Scholar 

  80. Ficz G, Branco MR, Seisenberger S et al (2011) Dynamic regulation of 5-hydroxymethylcytosine in mouse ES cells and during differentiation. Nature 473:398–402

    Article  PubMed  CAS  Google Scholar 

  81. Stouder C, Paoloni-Giacobino A (2010) Transgenerational effects of the endocrine disruptor vinclozolin on the methylation pattern of imprinted genes in the mouse sperm. Reproduction 139:373–379

    Article  PubMed  CAS  Google Scholar 

  82. Hammoud SS, Nix DA, Zhang H, Purwar J, Carrell DT, Cairns BR (2009) Distinctive chromatin in human sperm packages genes for embryo development. Nature 460:473–478

    PubMed  CAS  Google Scholar 

  83. Greer EL, Maures TJ, Hauswirth AG et al (2010) Members of the H3K4 trimethylation complex regulate lifespan in a germline-dependent manner in C. elegans. Nature 466:383–387

    Article  PubMed  CAS  Google Scholar 

  84. Greer EL, Maures TJ, Ucar D et al (2011) Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479:365–371

    Article  PubMed  CAS  Google Scholar 

  85. Li T, Kelly WG (2011) A role for Set1/MLL-related components in epigenetic regulation of the Caenorhabditis elegans germ line. PLoS Genet 7:e1001349

    Article  PubMed  CAS  Google Scholar 

  86. Seong KH, Li D, Shimizu H, Nakamura R, Ishii S (2011) Inheritance of stress-induced, ATF-2-dependent epigenetic change. Cell 145:1049–1061

    Article  PubMed  CAS  Google Scholar 

  87. Vastenhouw NL, Brunschwig K, Okihara KL, Muller F, Tijsterman M, Plasterk RH (2006) Gene expression: long-term gene silencing by RNAi. Nature 442:882

    Article  PubMed  CAS  Google Scholar 

  88. Alcazar RM, Lin R, Fire AZ (2008) Transmission dynamics of heritable silencing induced by double-stranded RNA in Caenorhabditis elegans. Genetics 180:1275–1288

    Article  PubMed  CAS  Google Scholar 

  89. Buckley BA, Burkhart KB, Gu SG et al (2012) A nuclear Argonaute promotes multigenerational epigenetic inheritance and germline immortality. Nature 489:447–451

    Article  PubMed  CAS  Google Scholar 

  90. Ashe A, Sapetschnig A, Weick EM et al (2012) piRNAs can trigger a multigenerational epigenetic memory in the germline of C. elegans. Cell 150:88–99

    Article  PubMed  CAS  Google Scholar 

  91. Bagijn MP, Goldstein LD, Sapetschnig A et al (2012) Function, targets, and evolution of Caenorhabditis elegans piRNAs. Science 337:574–578

    Article  PubMed  CAS  Google Scholar 

  92. Lee HC, Gu W, Shirayama M, Youngman E, Conte D Jr, Mello CC (2012) C. elegans piRNAs mediate the genome-wide surveillance of germline transcripts. Cell 150:78–87

    Article  PubMed  CAS  Google Scholar 

  93. Gu SG, Pak J, Guang S, Maniar JM, Kennedy S, Fire A (2012) Amplification of siRNA in Caenorhabditis elegans generates a transgenerational sequence-targeted histone H3 lysine 9 methylation footprint. Nat Genet 44:157–164

    Article  PubMed  CAS  Google Scholar 

  94. Rechavi O, Minevich G, Hobert O (2011) Transgenerational inheritance of an acquired small RNA-based antiviral response in C. elegans. Cell 147:1248–1256

    Article  PubMed  CAS  Google Scholar 

  95. Brennecke J, Malone CD, Aravin AA, Sachidanandam R, Stark A, Hannon GJ (2008) An epigenetic role for maternally inherited piRNAs in transposon silencing. Science 322:1387–1392

    Article  PubMed  CAS  Google Scholar 

  96. Kuramochi-Miyagawa S, Watanabe T, Gotoh K et al (2008) DNA methylation of retrotransposon genes is regulated by Piwi family members MILI and MIWI2 in murine fetal testes. Genes Dev 22:908–917

    Article  PubMed  CAS  Google Scholar 

  97. Watanabe T, Tomizawa S, Mitsuya K et al (2011) Role for piRNAs and noncoding RNA in de novo DNA methylation of the imprinted mouse Rasgrf1 locus. Science 332:848–852

    Article  PubMed  CAS  Google Scholar 

  98. Aravin AA, Sachidanandam R, Girard A, Fejes-Toth K, Hannon GJ (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316:744–747

    Article  PubMed  CAS  Google Scholar 

  99. Wagner KD, Wagner N, Ghanbarian H et al (2008) RNA induction and inheritance of epigenetic cardiac hypertrophy in the mouse. Dev Cell 14:962–969

    Article  PubMed  CAS  Google Scholar 

  100. Grandjean V, Gounon P, Wagner N et al (2009) The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth. Development 136:3647–3655

    Article  PubMed  CAS  Google Scholar 

  101. Reik W, Romer I, Barton SC, Surani MA, Howlett SK, Klose J (1993) Adult phenotype in the mouse can be affected by epigenetic events in the early embryo. Development 119:933–942

    PubMed  CAS  Google Scholar 

  102. Kaminsky ZA, Tang T, Wang SC et al (2009) DNA methylation profiles in monozygotic and dizygotic twins. Nat Genet 41:240–245

    Article  PubMed  CAS  Google Scholar 

  103. Fraga MF, Ballestar E, Paz MF et al (2005) Epigenetic differences arise during the lifetime of monozygotic twins. Proc Natl Acad Sci USA 102:10604–10609

    Article  PubMed  CAS  Google Scholar 

  104. Heijmans BT, Tobi EW, Stein AD et al (2008) Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA 105:17046–17049

    Article  PubMed  CAS  Google Scholar 

  105. Tobi EW, Lumey LH, Talens RP et al (2009) DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet 18:4046–4053

    Article  PubMed  CAS  Google Scholar 

  106. Waterland RA, Kellermayer R, Laritsky E et al (2010) Season of conception in rural gambia affects DNA methylation at putative human metastable epialleles. PLoS Genet 6:e1001252

    Article  PubMed  CAS  Google Scholar 

  107. Godfrey KM, Sheppard A, Gluckman PD et al (2011) Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes 60:1528–1534

    Article  PubMed  CAS  Google Scholar 

  108. Lane N, Dean W, Erhardt S et al (2003) Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35:88–93

    Article  PubMed  CAS  Google Scholar 

  109. Petruk S, Sedkov Y, Johnston DM et al (2012) TrxG and PcG proteins but not methylated histones remain associated with DNA through replication. Cell 150:922–933

    Article  PubMed  CAS  Google Scholar 

  110. Branco MR, Ficz G, Reik W (2012) Uncovering the role of 5-hydroxymethylcytosine in the epigenome. Nat Rev Genet 13:7–13

    CAS  Google Scholar 

  111. Palmer NO, Bakos HW, Owens JA, Setchell BP, Lane M (2012) Diet and exercise in an obese mouse fed a high-fat diet improve metabolic health and reverse perturbed sperm function. Am J Physiol Endocrinol Metab 302:E768–E780

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA

    Mary-Elizabeth Patti

Authors
  1. Mary-Elizabeth Patti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mary-Elizabeth Patti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Patti, ME. Intergenerational programming of metabolic disease: evidence from human populations and experimental animal models. Cell. Mol. Life Sci. 70, 1597–1608 (2013). https://doi.org/10.1007/s00018-013-1298-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-013-1298-0

Keywords

Search

Navigation