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Transgenerational transmission of pregestational and prenatal experience: maternal adversity, enrichment, and underlying epigenetic and environmental mechanisms

Part of: Prenatal Origins of Adult Mental Health and Illness

Published online by Cambridge University Press:  04 August 2016

L. Taouk  and
J. Schulkin
L. Taouk
Affiliation:
Department of Psychology, American University, Washington, DC, USA Department of Research, The American College of Obstetricians and Gynecologists, Washington, DC, USA
J. Schulkin*
Affiliation:
Department of Research, The American College of Obstetricians and Gynecologists, Washington, DC, USA Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, WA, USA Department of Neuroscience, Georgetown University, Washington, DC, USA
*
*Address for correspondence: J. Schulkin, Department of Neuroscience, Georgetown University, 3700 O St. NW, Washington, DC 20057, USA. (Email jschulkin@acog.org)
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Abstract

Transgenerational transmission refers to positive and negative adaptations in brain function and behavior that affect following generations. In this paper, empirical findings regarding the transgenerational transmission of maternal adversity during three critical periods – childhood, pregestational adulthood and pregnancy – will be reviewed in terms of pregnancy outcomes, maternal care, offspring behavior and development, and physiological functioning. Research on the transgenerational transmission of enrichment and the implications for interventions to ameliorate the consequences of adversity will also be presented. In the final section, underlying epigenetic and environmental mechanisms that have been proposed to explain how experience is transferred across generations through transgenerational transmission will be reviewed. Directions for future research are suggested throughout.

Keywords

adversityenrichmentepigeneticsprenatal/pregestationaltransgenerational

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Type
Review
Information
Journal of Developmental Origins of Health and Disease , Volume 7 , Issue 6: Themed Issue: Developmental Origins of Adult Mental Health and Illness , December 2016 , pp. 588 - 601
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© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2016 

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References

1. Youngson, NA, Whitelaw, E. Transgenerational epigenetic effects. Annu Rev Genomics Hum Genet. 2008; 9, 233–257.CrossRefGoogle ScholarPubMed
2. Champagne, FA. Epigenetic influence of social experiences across the lifespan. Dev Psychopathol. 2010; 52, 299–311.Google ScholarPubMed
3. Feldman, R, Vengrober, A. Posttraumatic stress disorder in infants and young children exposed to war-related trauma. J Am Acad Child Adolesc Psychiatry. 2011; 50, 645–658.CrossRefGoogle ScholarPubMed
4. Noll, JG. Sexual abuse of children – unique in its effects on development? Child Abuse Negl. 2008; 32, 603–605.CrossRefGoogle ScholarPubMed
5. Brodsky, BS, Mann, JJ, Stanley, B, et al. Familial transmission of suicidal behavior: factors mediating the relationship between childhood abuse and offspring suicide attempts. J Clin Psychiatry. 2008; 69, 584–596.CrossRefGoogle ScholarPubMed
6. Molnar, BE, Buka, SL, Kessler, RC. Child sexual abuse and subsequent psychopathology: results from the National Comorbidity Survey. Am J Public Health. 2001; 91, 753–760.Google ScholarPubMed
7. McCauley, J, Kern, DE, Kolodner, K, et al. Clinical characteristics of women with a history of childhood abuse: unhealed wounds. JAMA. 1997; 277, 1362–1368.CrossRefGoogle ScholarPubMed
8. MacMillan, H, Fleming, J, Streiner, D, et al. Childhood abuse and lifetime psychopathology in a community sample. Am J Psychiatry. 2001; 158, 1878–1883.CrossRefGoogle Scholar
9. Farber, EW, Herbert, SE, Reviere, SL. Childhood abuse and suicidality in obstetrics patients in a hospital-based urban prenatal clinic. Gen Hosp Psychiatry. 1996; 18, 56–60.CrossRefGoogle Scholar
10. Wosu, AC, Gelaye, B, Williams, MA. Maternal history of childhood sexual abuse and preterm birth: an epidemiologic review. BMC Pregnancy Childbirth. 2015; 15, 174.CrossRefGoogle ScholarPubMed
11. Moster, D, Lie, RT, Markestad, T. Long-term medical and social consequences of preterm birth. N Engl J Med. 2008; 359, 262–273.CrossRefGoogle ScholarPubMed
12. Leshem, M, Schulkin, J. Transgenerational effects of infantile adversity and enrichment in male and female rats. Dev Psychobiol. 2012; 54, 169–186.CrossRefGoogle ScholarPubMed
13. Franklin, TB, Russig, H, Weiss, IC, et al. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry. 2010; 68, 408–415.CrossRefGoogle Scholar
14. Field, T, Diego, M, Hernandez-Reif, M, et al. Prenatal maternal cortisol, fetal activity and growth. Int J Neurosci. 2005; 115, 423–429.CrossRefGoogle ScholarPubMed
15. Bremner, JD, Vythilingam, M, Vermetten, E, et al. Cortisol response to a cognitive stress challenge in posttraumatic stress disorder (PTSD) related to childhood abuse. Psychoneuroendocrinology. 2003; 28, 733–750.CrossRefGoogle ScholarPubMed
16. Austin, MP, Leader, LR, Reilly, N. Prenatal stress, the hypothalamic–pituitary–adrenal axis, and fetal and infant neurobehaviour. Early Hum Dev. 2005; 81, 917–926.CrossRefGoogle ScholarPubMed
17. Lupien, SJ, McEwen, BS, Gunnar, MR, et al. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci. 2009; 10, 434–445.CrossRefGoogle ScholarPubMed
18. Noll, JG, Schulkin, J, Trickett, PK, et al. Differential pathways to preterm delivery for sexually abused and comparison women. J Pediatr Psychol. 2007; 32, 1238–1248.CrossRefGoogle ScholarPubMed
19. Horan, DL, Hill, LD, Schulkin, J. Childhood sexual abuse and preterm labor in adulthood: an endocrinological hypothesis. Womens Health Issues. 2000; 10, 27–33.CrossRefGoogle ScholarPubMed
20. Moog, NK, Buss, C, Entringer, S, et al. Maternal exposure to childhood trauma is associated during pregnancy with placental-fetal stress physiology. Biol Psychiatry. 2015; 29, 831–839.Google Scholar
21. McGowan, PO, Sasaki, A, D’Alessio, AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci. 2009; 12, 342–348.CrossRefGoogle ScholarPubMed
22. Hyman, SE. How adversity gets under the skin. Nat Neurosci. 2009; 12, 241–243.CrossRefGoogle ScholarPubMed
23. Naumova, OY, Lee, M, Koposov, R, et al. Differential patterns of whole-genome DNA methylation in institutionalized children and children raised by their biological parents. Dev Psychopathol. 2012; 24, 143–155.CrossRefGoogle ScholarPubMed
24. Roth, TL, Lubin, FD, Funk, AJ, et al. Lasting epigenetic influence of early-life adversity on the BDNF gene. Biol Psychiatry. 2009; 65, 760–769.CrossRefGoogle ScholarPubMed
25. Collishaw, S, Dunn, J, O’connor, TG, et al. Maternal childhood abuse and offspring adjustment over time. Dev Psychopathol. 2007; 19, 367–383.CrossRefGoogle ScholarPubMed
26. Shachar-Dadon, A, Schulkin, J, Leshem, M. Adversity before conception will affect adult progeny in rats. Dev Psychol. 2009; 45, 9–16.CrossRefGoogle ScholarPubMed
27. Zaidan, H, Leshem, M, Gaisler-Salomon, I. Pregestational stress to female rats alters corticotropin releasing factor type 1 expression in ova and behavior and brain corticotropin releasing factor type 1 expression in offspring. Biol Psychiatry. 2013; 74, 680–687.CrossRefGoogle Scholar
28. Zaidan, H, Gaisler-Salomon, I. Pregestational stress in adolescent female rats affects behavior and corticosterone levels in second-generation offspring. Psychoneuroendocrinology. 2015; 58, 120–129.CrossRefGoogle Scholar
29. Bock, J, Poeschel, J, Schindler, J, et al. Transgenerational sex-specific impact of preconception stress on the development of dendritic spines and dendritic length in the medial prefrontal cortex. Brain Struct Funct. 2014; 221, 855–863.CrossRefGoogle ScholarPubMed
30. Champagne, FA, Francis, DD, Mar, A, et al. Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol Behav. 2003; 79, 359–371.CrossRefGoogle ScholarPubMed
31. Weinstock, M. The long-term behavioral consequences of prenatal stress. Neurosci Biobehav Rev. 2008; 32, 1073–1086.CrossRefGoogle ScholarPubMed
32. Monk, C, Spicer, J, Champagne, FA. Linking prenatal maternal adversity to developmental outcomes in infants: the role of epigenetic pathways. Dev Psychopathol. 2012; 24, 1361–1376.CrossRefGoogle ScholarPubMed
33. Champagne, FA, Meaney, MJ. Stress during gestation alters postpartum maternal care and the development of the offspring in a rodent model. Biol Psychiatry. 2006; 59, 1227–1235.CrossRefGoogle Scholar
34. Lehmann, J, Stöhr, T, Feldon, J. Long-term effects of prenatal stress experience and postnatal maternal separation on emotionality and attentional processes. Behav Brain Res. 2000; 107, 133–144.CrossRefGoogle ScholarPubMed
35. Fujioka, T, Fujioka, A, Tan, N, et al. Mild prenatal stress enhances learning performance in the non-adopted rat offspring. Neuroscience. 2001; 103, 301–307.CrossRefGoogle ScholarPubMed
36. Bale, TL. Sex differences in prenatal epigenetic programming of stress pathways. Stress. 2011; 14, 348–356.CrossRefGoogle ScholarPubMed
37. Koenig, JI, Elmer, GI, Shepard, PD, et al. Prenatal exposure to a repeated variable stress paradigm elicits behavioral and neuroendocrinological changes in the adult offspring: potential relevance to schizophrenia. Behav Brain Res. 2005; 156, 251–261.CrossRefGoogle ScholarPubMed
38. Kapoor, A, Dunn, E, Kostaki, A, et al. Fetal programming of hypothalamo‐pituitary‐adrenal function: prenatal stress and glucocorticoids. J Physiol. 2006; 572, 31–44.CrossRefGoogle ScholarPubMed
39. Weinstock, M. Sex-dependent changes induced by prenatal stress in cortical and hippocampal morphology and behaviour in rats: an update. Stress. 2011; 14, 604–613.CrossRefGoogle ScholarPubMed
40. Mueller, BR, Bale, TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008; 28, 9055–9065.CrossRefGoogle ScholarPubMed
41. Grundwald, NJ, Brunton, PJ. Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner. Psychoneuroendocrinology. 2015; 62, 204–216.CrossRefGoogle Scholar
42. Welberg, LA, Seckl, JR, Holmes, MC. Inhibition of 11β‐hydroxysteroid dehydrogenase, the foeto‐placental barrier to maternal glucocorticoids, permanently programs amygdala GR mRNA expression and anxiety‐like behaviour in the offspring. Eur J Neurosci. 2000; 12, 1047–1054.CrossRefGoogle ScholarPubMed
43. Bingham, BC, Rani, CS, Frazer, A, et al. Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior. Psychoneuroendocrinology. 2013; 38, 2746–2757.CrossRefGoogle ScholarPubMed
44. Oberlander, TF, Weinberg, J, Papsdorf, M, et al. Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics. 2008; 3, 97–106.CrossRefGoogle ScholarPubMed
45. Radtke, KM, Ruf, M, Gunter, HM, et al. Transgenerational impact of intimate partner violence on methylation in the promoter of the glucocorticoid receptor. Transl Psychiatry. 2011; 1, e21.CrossRefGoogle ScholarPubMed
46. Leung, E, Tasker, SL, Atkinson, L, et al. Perceived maternal stress during pregnancy and its relation to infant stress reactivity at 2 days and 10 months of postnatal life. Clin Pediatr. 2010; 49, 158–165.CrossRefGoogle ScholarPubMed
47. Davis, EP, Glynn, LM, Waffarn, F, et al. Prenatal maternal stress programs infant stress regulation. J Child Psychol Psychiatry. 2011; 52, 119–129.CrossRefGoogle ScholarPubMed
48. Yehuda, R, Engel, SM, Brand, SR, et al. Transgenerational effects of posttraumatic stress disorder in babies of mothers exposed to the World Trade Center attacks during pregnancy. J Clin Endocrinol Metab. 2005; 90, 4115–4118.CrossRefGoogle Scholar
49. Curley, JP, Davidson, S, Bateson, P, et al. Social enrichment during postnatal development induces transgenerational effects on emotional and reproductive behavior in mice. Front Behav Neurosci. 2009; 3, published online.CrossRefGoogle ScholarPubMed
50. Cutuli, D, Caporali, P, Gelfo, F, et al. Pre-reproductive maternal enrichment influences rat maternal care and offspring developmental trajectories: behavioral performances and neuroplasticity correlates. Front Behav Neurosci. 2015; 9, published online.CrossRefGoogle ScholarPubMed
51. Laviola, G, Rea, M, Morley‐Fletcher, S, et al. Beneficial effects of enriched environment on adolescent rats from stressed pregnancies. Eur J Neurosci. 2004; 20, 1655–1664.CrossRefGoogle ScholarPubMed
52. Poltyrev, T, Gorodetsky, E, Bejar, C, et al. Effect of chronic treatment with ladostigil (TV-3326) on anxiogenic and depressive-like behaviour and on activity of the hypothalamic–pituitary–adrenal axis in male and female prenatally stressed rats. Psychopharmacology. 2005; 181, 118–125.CrossRefGoogle ScholarPubMed
53. Arai, JA, Li, S, Hartley, DM, et al. Transgenerational rescue of a genetic defect in long-term potentiation and memory formation by juvenile enrichment. J Neurosci. 2009; 29, 1496–1502.CrossRefGoogle ScholarPubMed
54. Welberg, L, Thrivikraman, KV, Plotsky, PM. Combined pre-and postnatal environmental enrichment programs the HPA axis differentially in male and female rats. Psychoneuroendocrinology. 2006; 31, 553–564.CrossRefGoogle ScholarPubMed
55. Maruoka, T, Kodomari, I, Yamauchi, R, et al. Maternal enrichment affects prenatal hippocampal proliferation and open-field behaviors in female offspring mice. Neurosci Lett. 2009; 454, 28–32.CrossRefGoogle ScholarPubMed
56. Yehuda, R, Bierer, LM. The relevance of epigenetics to PTSD: implications for the DSM-V. J Trauma Stress. 2009; 22, 427–434.CrossRefGoogle ScholarPubMed
57. Perrin, MC, Brown, AS, Malaspina, D. Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia. Schizophr Bull. 2007; 33, 1270–1273.CrossRefGoogle ScholarPubMed
58. McGowan, PO, Roth, TL. Epigenetic pathways through which experiences become linked with biology. Dev Psychopathol. 2015; 27, 637–648.CrossRefGoogle ScholarPubMed
59. Cottrell, EC, Seckl, JR. Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci. 2009; 3, published online.CrossRefGoogle ScholarPubMed
60. Abou-Seif, C, Shipman, KL, Allars, M, et al. Tissue specific epigenetic differences in CRH gene expression. Front Biosci. 2011; 17, 713–725.CrossRefGoogle Scholar
61. Di Stefano, V, Wang, B, Parobchak, N, et al. RelB/p52-mediated NF-κB signaling alters histone acetylation to increase the abundance of corticotropin-releasing hormone in human placenta. Sci Signal. 2015; 8, ra85.CrossRefGoogle ScholarPubMed
62. Erickson, K, Thorsen, P, Chrousos, G, et al. Preterm birth: associated neuroendocrine, medical, and behavioral risk factors 1. J Clin Endocrinol Metab. 2001; 86, 2544–2552.Google Scholar
63. Majzoub, JA. Corticotropin-releasing hormone physiology. Eur J Endocrinol. 2006; 155(Suppl. 1), S71–S76.CrossRefGoogle Scholar
64. McLean, M, Bisits, A, Davies, J, et al. A placental clock controlling the length of human pregnancy. Nat Med. 1995; 1, 460–463.CrossRefGoogle ScholarPubMed
65. Power, ML, Schulkin, J. Feature article functions of corticotropin-releasing hormone in anthropoid primates: from brain to placenta. Am J Hum Biol. 2006; 18, 431–447.CrossRefGoogle Scholar
66. Meltzer-Brody, S, Stuebe, A, Dole, N, et al. Elevated corticotropin releasing hormone (CRH) during pregnancy and risk of postpartum depression (PPD). J Clin Endocrinol Metab. 2011; 96, E40–E47.CrossRefGoogle ScholarPubMed
67. Yim, IS, Glynn, LM, Schetter, CD, et al. Elevated corticotropin-releasing hormone in human pregnancy increases the risk of postpartum depressive symptoms. Arch Gen Psychiatry. 2009; 66, 162–169.CrossRefGoogle ScholarPubMed
68. Engineer, N, Darwin, L, Nishigandh, D, et al. Association of glucocorticoid and type 1 corticotropin-releasing hormone receptors gene variants and risk for depression during pregnancy and post-partum. J Psychiatr Res. 2013; 47, 1166–1173.CrossRefGoogle ScholarPubMed
69. Curley, JP, Jensen, CL, Mashoodh, R, et al. Social influences on neurobiology and behavior: epigenetic effects during development. Psychoneuroendocrinology. 2011; 36, 352–371.CrossRefGoogle ScholarPubMed
70. Elliott, E, Ezra-Nevo, G, Regev, L, et al. Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice. Nat Neurosci. 2010; 13, 1351–1353.CrossRefGoogle ScholarPubMed
71. Francis, DD, Champagne, FC, Meaney, MJ. Variations in maternal behaviour are associated with differences in oxytocin receptor levels in the rat. J Neuroendocrinol. 2000; 12, 1145–1148.CrossRefGoogle ScholarPubMed
72. Erickson, K, Gabry, KE, Schulkin, J, et al. Social withdrawal behaviors in nonhuman primates and changes in neuroendocrine and monoamine concentrations during a separation paradigm. Dev Psychobiol. 2005; 46, 331–339.CrossRefGoogle ScholarPubMed
73. Winslow, JT, Noble, PL, Lyons, CK, et al. Rearing effects on cerebrospinal fluid oxytocin concentration and social buffering in rhesus monkeys. Neuropsychopharmacology. 2003; 28, 910–918.CrossRefGoogle ScholarPubMed
74. Rosenblum, LA, Smith, EL, Altemus, M, et al. Differing concentrations of corticotropin-releasing factor and oxytocin in the cerebrospinal fluid of bonnet and pigtail macaques. Psychoneuroendocrinology. 2002; 27, 651–660.CrossRefGoogle ScholarPubMed
75. Kinnally, EL, Capitanio, JP, Leibel, R, et al. Epigenetic regulation of serotonin transporter expression and behavior in infant rhesus macaques. Genes Brain Behav. 2010; 9, 575–582.CrossRefGoogle ScholarPubMed
76. Meaney, MJ. Maternal care, gene expression, and the transmission of individual differences in stress reactivity across generations. Annu Rev Neurosci. 2001; 24, 1161–1192.CrossRefGoogle Scholar
77. Curley, JP, Champagne, FA, Bateson, P, et al. Transgenerational effects of impaired maternal care on behaviour of offspring and grand offspring. Anim Behav. 2008; 75, 1551–1561.CrossRefGoogle Scholar
78. Champagne, FA, Curley, JP. Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci Biobehav Rev. 2009; 33, 593–600.CrossRefGoogle ScholarPubMed
79. Weaver, IC, Cervoni, N, Champagne, FA, et al. Epigenetic programming by maternal behavior. Nat Neurosci. 2004; 7, 847–854.CrossRefGoogle ScholarPubMed
80. Gos, T, Schulkin, J, Gos, A. Paternal deprivation affects the functional maturation of corticotropin-releasing hormone (CRH)-and calbindin-D28k-expressing neurons in the bed nucleus of the stria terminalis (BNST) of the biparental Octodon degus . Brain Struct Funct. 2014; 219, 1983–1990.CrossRefGoogle ScholarPubMed
81. Braun, K, Seidel, K, Holetschka, R, et al. Paternal deprivation alters the development of catecholaminergic innervation in the prefrontal cortex and related limbic brain regions. Brain Struct Funct. 2013; 218, 859–872.CrossRefGoogle ScholarPubMed
82. Seidel, K, Poeggel, G, Holetschka, R, et al. Paternal deprivation affects the development of corticotrophin‐releasing factor‐expressing neurones in prefrontal cortex, amygdala and hippocampus of the biparental Octodon degus . J Neuroendocrinol. 2011; 23, 1166–1176.CrossRefGoogle ScholarPubMed
83. Yehuda, R. Are different biological mechanisms involved in the transmission of maternal versus paternal stress-induced vulnerability to offspring? Biol Psychiatry. 2011; 70, 402–403.CrossRefGoogle ScholarPubMed
84. Dietz, DM, Laplant, Q, Watts, EL, et al. Paternal transmission of stress-induced pathologies. Biol Psychiatry. 2011; 70, 408–414.CrossRefGoogle ScholarPubMed
85. Malaspina, D, Reichenberg, A, Weiser, M, et al. Paternal age and intelligence: implications for age-related genomic changes in male germ cells. Psychiatr Genet. 2005; 15, 117–125.CrossRefGoogle ScholarPubMed
86. Curley, JP, Mashoodh, R, Champagne, FA. Epigenetics and the origins of paternal effects. Horm Behav. 2011; 59, 306–314.CrossRefGoogle ScholarPubMed
87. Giesing, ER, Suski, CD, Warner, RE, et al. Female sticklebacks transfer information via eggs: effects of maternal experience with predators on offspring. Proc R Soc Lond B Biol Sci. 2011; 278, 1753–1759.Google ScholarPubMed
88. Mashoodh, R, Sinal, CJ, Perrot-Sinal, TS. Predation threat exerts specific effects on rat maternal behaviour and anxiety-related behaviour of male and female offspring. Physiol Behav. 2009; 96, 693–702.CrossRefGoogle ScholarPubMed
89. Pembrey, M, Saffery, R, Bygren, LO, et al. Human transgenerational responses to early-life experience: potential impact on development, health and biomedical research. J Med Genet. 2014; 51, 563–572.CrossRefGoogle ScholarPubMed
90. Painter, RC, Roseboom, TJ, Bleker, OP. Prenatal exposure to the Dutch famine and disease in later life: an overview. Reprod Toxicol. 2005; 20, 345–352.CrossRefGoogle Scholar
91. Painter, RC, Osmond, C, Gluckman, P, et al. Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life. BJOG. 2008; 115, 1243–1249.CrossRefGoogle Scholar
92. Bygren, LO, Tinghög, P, Carstensen, J, et al. Change in paternal grandmothers early food supply influenced cardiovascular mortality of the female grandchildren. BMC Genet. 2014; 15, 12.CrossRefGoogle ScholarPubMed
93. Pembrey, ME, Bygren, LO, Kaati, G, et al. Sex-specific, male-line transgenerational responses in humans. Eur J Hum Genet. 2006; 14, 159–166.CrossRefGoogle ScholarPubMed
94. Kaati, G, Bygren, LO, Pembrey, M, et al. Transgenerational response to nutrition, early life circumstances and longevity. Eur J Hum Genet. 2007; 15, 784–790.CrossRefGoogle ScholarPubMed
95. Entringer, S, Buss, C, Swanson, JM, et al. Fetal programming of body composition, obesity, and metabolic function: the role of intrauterine stress and stress biology. J Nutr Metab. 2012; published online.CrossRefGoogle ScholarPubMed
96. Wang, G, Walker, SO, Hong, X, et al. Epigenetics and early life origins of chronic noncommunicable diseases. J Adolesc Health. 2013; 52, S14–S21.CrossRefGoogle ScholarPubMed
97. Heijmans, BT, Tobi, EW, Stein, AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008; 105, 17046–17049.CrossRefGoogle ScholarPubMed
98. Tobi, EW, Lumey, LH, Talens, RP, et al. DNA methylation differences after exposure to prenatal famine are common and timing- and sex-specific. Hum Mol Genet. 2009; 18, 4046–4053.CrossRefGoogle ScholarPubMed
99. Godfrey, KM, Sheppard, A, Gluckman, PD, et al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes. 2011; 60, 1528–1534.CrossRefGoogle ScholarPubMed
100. Li, M, Fallin, MD, Riley, A, et al. The association of maternal obesity and diabetes with autism and other developmental disabilities. Pediatrics. 2016; 137, published online.CrossRefGoogle ScholarPubMed
101. Waterland, RA, Garza, C. Potential mechanisms of metabolic imprinting that lead to chronic disease. Am J Clin Nutr. 1999; 69, 179–197.CrossRefGoogle ScholarPubMed
102. Hong, X, Wang, X. Early life precursors, epigenetics, and the development of food allergy. Semin Immunopath. 2012; 34, 655–669.CrossRefGoogle ScholarPubMed
103. Hong, X, Wang, X. Epigenetics and development of food allergy (FA) in early childhood. Curr Allergy Asthma Rep. 2014; 14, 460.CrossRefGoogle ScholarPubMed
104. Hong, X, Hao, K, Ladd-Acosta, C, et al. Genome-wide association study identifies peanut allergy-specific loci and evidence of epigenetic mediation in US children. Nat Commun. 2015; 6, 1–12.CrossRefGoogle ScholarPubMed
105. Lee, MH, Jeon, YJ, Lee, SM, et al. Placental gene expression is related to glucose metabolism and fetal cord blood levels of insulin and insulin-like growth factors in intrauterine growth restriction. Early Hum Dev. 2010; 86, 45–50.CrossRefGoogle ScholarPubMed
106. Entringer, S, Buss, C, Wadhwa, PD. Prenatal stress, development, health and disease risk: a psychobiological perspective. Psychoneuroendocrinology. 2015; 62, 366–375.CrossRefGoogle Scholar
107. Banks, WA. A vagina monologue: mom’s stress, bugs, and baby’s brain. Endocrinology. 2015; 156, 3066–3068.CrossRefGoogle ScholarPubMed