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Early post-conception maternal cortisol, children’s HPAA activity and DNA methylation profiles

Part of: A Canadian perspective on DOHaD

Published online by Cambridge University Press:  15 November 2018

C. K. Barha ,
K. G. Salvante ,
M. J. Jones ,
P. Farré ,
J. Blais ,
M. S. Kobor ,
L. Zeng ,
E. Emberly  and
P. A. Nepomnaschy
C. K. Barha
Affiliation:
Maternal and Child Health Lab, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
K. G. Salvante
Affiliation:
Maternal and Child Health Lab, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada
M. J. Jones
Affiliation:
Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, Vancouver, BC, Canada Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada
P. Farré
Affiliation:
Department of Physics, Simon Fraser University, Burnaby, BC, Canada
J. Blais
Affiliation:
Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada
M. S. Kobor
Affiliation:
Centre for Molecular Medicine and Therapeutics, BC Children’s Hospital Research Institute, Vancouver, BC, Canada Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Human Early Learning Partnership, School of Population and Public Health, University of British Columbia, Vancouver, BC, Canada
L. Zeng
Affiliation:
Department of Statistics and Actuarial Science, University of Waterloo, Waterloo, ON, Canada
E. Emberly
Affiliation:
Department of Physics, Simon Fraser University, Burnaby, BC, Canada
P. A. Nepomnaschy
Affiliation:
Maternal and Child Health Lab, Faculty of Health Sciences, Simon Fraser University, Burnaby, BC, Canada Crawford Laboratory of Evolutionary Studies, Simon Fraser University, Burnaby, BC, Canada
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Abstract

The hypothalamic–pituitary–adrenal axis (HPAA) plays a critical role in the functioning of all other biological systems. Thus, studying how the environment may influence its ontogeny is paramount to understanding developmental origins of health and disease. The early post-conceptional (EPC) period could be particularly important for the HPAA as the effects of exposures on organisms’ first cells can be transmitted through all cell lineages. We evaluate putative relationships between EPC maternal cortisol levels, a marker of physiologic stress, and their children’s pre-pubertal HPAA activity (n=22 dyads). Maternal first-morning urinary (FMU) cortisol, collected every-other-day during the first 8 weeks post-conception, was associated with children’s FMU cortisol collected daily around the start of the school year, a non-experimental challenge, as well as salivary cortisol responses to an experimental challenge (all Ps<0.05), with some sex-related differences. We investigated whether epigenetic mechanisms statistically mediated these links and, therefore, could provide cues as to possible biological pathways involved. EPC cortisol was associated with >5% change in children’s buccal epithelial cells’ DNA methylation for 867 sites, while children’s HPAA activity was associated with five CpG sites. Yet, no CpG sites were related to both, EPC cortisol and children’s HPAA activity. Thus, these epigenetic modifications did not statistically mediate the observed physiological links. Larger, prospective peri-conceptional cohort studies including frequent bio-specimen collection from mothers and children will be required to replicate our analyses and, if our results are confirmed, identify biological mechanisms mediating the statistical links observed between maternal EPC cortisol and children’s HPAA activity.

Keywords

child developmentcortisolDNA methylationearly post-conceptionhypothalamic–pituitary–adrenal axissex differences
Type
Original Article
Information
Journal of Developmental Origins of Health and Disease , Volume 10 , Special Issue 1: Themed Issue: Canada / Indigenous Populations , February 2019 , pp. 73 - 87
Copyright
© Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2018. 

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Footnotes

a

Current address: Faculty of Medicine, Department of Physical Therapy, University of British Columbia, Vancouver, BC, Canada

b

Current address: Department of Biochemistry and Medical Genetics, Max Rady College of Medicine, University of Manitoba, Winnipeg, MB, Canada

†

Both authors contributed equally to this work

References

1. McEwen, BS. Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Ann N Y Acad Sci. 2004; 1032, 1–7.Google Scholar
2. Nepomnaschy, PA, Welch, K, McConnell, D, Strassmann, BI, England, BG. Stress and female reproductive function: a study of daily variations in cortisol, gonadotrophins, and gonadal steroids in a rural Mayan population. Am J Hum Biol. 2004; 16, 523–532.Google Scholar
3. Nepomnaschy, PA, Welch, KB, McConnell, DS, et al. Cortisol levels and very early pregnancy loss in humans. Proc Natl Acad Sci USA. 2006; 103, 3938–3942.Google Scholar
4. Provencal, N, Binder, EB. The effects of early life stress on the epigenome: from the womb to adulthood and even before. Exp Neurol. 2015; 268, 10–20.Google Scholar
5. Reynolds, RM, Labad, J, Buss, C, Ghaemmaghami, P, Raikkonen, K. Transmitting biological effects of stress in utero: implications for mother and offspring. Psychoneuroendocrinology. 2013; 38, 1843–1849.Google Scholar
6. O’Connor, TG, Ben-Shlomo, Y, Heron, J, et al. Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children. Biol Psych. 2005; 58, 211–217.Google Scholar
7. Karlen, J, Frostell, A, Theodorsson, E, Faresjo, T, Ludvigsson, J. Maternal influence on child HPA axis: a prospective study of cortisol levels in hair. Pediatrics. 2013; 132, e1333–e1340.Google Scholar
8. Challis, JR. Endocrine disorders in pregnancy: stress responses in children after maternal glucocorticoids. Nat Rev Endocrinol. 2012; 8, 629–630.Google Scholar
9. Del Giudice, M. Fetal programming by maternal stress: insights from a conflict perspective. Psychoneuroendocrinology. 2012; 37, 1614–1629.Google Scholar
10. Moisiadis, VG, Matthews, SG. Glucocorticoids and fetal programming part 1: Outcomes. Nat Rev Endocrinol. 2014; 10, 391–402.Google Scholar
11. Iqbal, M, Moisiadis, VG, Kostaki, A, Matthews, SG. Transgenerational effects of prenatal synthetic glucocorticoids on hypothalamic-pituitary-adrenal function. Endocrinology. 2012; 153, 3295–3307.Google Scholar
12. Rossi-George, A, Virgolini, MB, Weston, D, Cory-Slechta, DA. Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: a potential biological unifying mechanism for their corresponding disease profiles. Toxicol Appl Pharmacol. 2009; 234, 117–127.Google Scholar
13. Maccari, S, Piazza, PV, Kabbaj, M, et al. Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress. J Neurosci. 1995; 15(1 Pt 1), 110–116.Google Scholar
14. Schöpper, H, Palme, R, Ruf, T, Huber, S. Effects of prenatal stress on hypothalamic-pituitary-adrenal (HPA) axis function over two generations of guinea pigs (Cavia aperea f. porcellus). Gen Comp Endocrinol. 2012; 176, 18–27.Google Scholar
15. Vieau, D, Sebaai, N, Leonhardt, M, et al. HPA axis programming by maternal undernutrition in the male rat offspring. Psychoneuroendocrinology. 2007; 32(Suppl 1), S16–20.Google Scholar
16. Yong Ping, E, Laplante, DP, Elgbeili, G, et al. Prenatal maternal stress predicts stress reactivity at 2(1/2) years of age: the Iowa Flood Study. Psychoneuroendocrinology. 2015; 56, 62–78.Google Scholar
17. Brunton, PJ, Russell, JA. Neuroendocrine control of maternal stress responses and fetal programming by stress in pregnancy. Prog Neuropsychopharmacol Biol Psychiatry. 2011; 35, 1178–1191.Google Scholar
18. Constantinof, A, Moisiadis, VG, Matthews, SG. Programming of stress pathways: a transgenerational perspective. J Ster Biochem Mol Biol. 2016; 160, 175–180.Google Scholar
19. Kapoor, A, Dunn, E, Kostaki, A, Andrews, MH, Matthews, SG. Fetal programming of hypothalamo-pituitary-adrenal function: prenatal stress and glucocorticoids. J Phys. 2006; 572(Pt 1), 31–44.Google Scholar
20. McGowan, PO, Sasaki, A, D’Alessio, AC, et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neurosci. 2009; 12, 342–348.Google Scholar
21. Meaney, MJ, Szyf, M, Seckl, JR. Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health. Trends Mol Med. 2007; 13, 269–277.Google Scholar
22. Torche, F, Kleinhaus, K. Prenatal stress, gestational age and secondary sex ratio: the sex-specific effects of exposure to a natural disaster in early pregnancy. Hum Reprod. 2012; 27, 558–567.Google Scholar
23. Mueller, BR, Bale, TL. Sex-specific programming of offspring emotionality after stress early in pregnancy. J Neurosci. 2008; 28, 9055–9065.Google Scholar
24. Kapoor, A, Kostaki, A, Janus, C, Matthews, SG. The effects of prenatal stress on learning in adult offspring is dependent on the timing of the stressor. Behav Brain Res. 2009; 197, 144–149.Google Scholar
25. Kapoor, A, Matthews, SG. Short periods of prenatal stress affect growth, behaviour and hypothalamo-pituitary-adrenal axis activity in male guinea pig offspring. J Phys. 2005; 566(Pt 3), 967–977.Google Scholar
26. Xu, J, Yang, B, Yan, C, et al. Effects of duration and timing of prenatal stress on hippocampal myelination and synaptophysin expression. Brain Res. 2013; 1527, 57–66.Google Scholar
27. Davis, EP, Sandman, CA. The timing of prenatal exposure to maternal cortisol and psychosocial stress is associated with human infant cognitive development. Child Dev. 2010; 81, 131–148.Google Scholar
28. van Os, J, Selten, JP. Prenatal exposure to maternal stress and subsequent schizophrenia. The May 1940 invasion of The Netherlands. Br J Psychiatry. 1998; 172, 324–326.Google Scholar
29. Lederman, SA, Rauh, V, Weiss, L, et al. The effects of the World Trade Center event on birth outcomes among term deliveries at three lower Manhattan hospitals. Environ Health Perspect. 2004; 112, 1772–1778.Google Scholar
30. Zhu, P, Huang, W, Hao, JH, et al. Time-specific effect of prenatal stressful life events on gestational weight gain. Int J Gynaecol Obstet. 2013; 122, 207–211.Google Scholar
31. Buss, C, Davis, EP, Shahbaba, B, et al. Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems. Proc Natl Acad Sci USA. 2012; 109, E1312–E1319.Google Scholar
32. Rakers, F, Frauendorf, V, Rupprecht, S, et al. Effects of early- and late-gestational maternal stress and synthetic glucocorticoid on development of the fetal hypothalamus-pituitary-adrenal axis in sheep. Stress. 2013; 16, 122–129.Google Scholar
33. Provencal, N, Binder, EB. The neurobiological effects of stress as contributors to psychiatric disorders: focus on epigenetics. Curr Opin Neurobiol. 2015; 30, 31–37.Google Scholar
34. 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.Google Scholar
35. Tobi, EW, Slagboom, PE, van Dongen, J, et al. Prenatal famine and genetic variation are independently and additively associated with DNA methylation at regulatory loci within IGF2/H19. PLoS One. 2012; 7, e37933–e37933.Google Scholar
36. Weinstock, M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev. 2008; 32, 1073–1086.Google Scholar
37. Schoenwolf, GC, Bleyl, SB, Brauer, PR, Francis-West, PH. Larsen’s Human Embryology. 2009. Churchill Livingstone Elsevier: Philadelphia.Google Scholar
38. Hochberg, Z, Feil, R, Constancia, M, et al. Child health, developmental plasticity, and epigenetic programming. Endoc Rev. 2010; 32, 159–224.Google Scholar
39. Cheong, JN, Wlodek, ME, Moritz, KM, Cuffe, JS. Programming of maternal and offspring disease: impact of growth restriction, fetal sex and transmission across generations. J Phys. 2016; 594, 4727–4740.Google Scholar
40. Ellison, PT. Fetal programming and fetal psychology. Infant Child Dev. 2010; 19, 6–20.Google Scholar
41. Essex MJ, Boyce WT, Hertzman C, et al. Epigenetic vestiges of early developmental adversity: Childhood stress exposure and DNA methylation in adolescence. Child Dev. 2013; https://doi.org/10.1111/j.1467-8624.2011.01641.x Google Scholar
42. Godfrey, KM, Lillycrop, KA, Burdge, GC, Gluckman, PD, Hanson, AM. Epigenetic mechanisms and the mismatch concept of the developmental origins of health and disease. Pediatr Res. 2007; 61, 5R–10R.Google Scholar
43. Hertzman, C. The biological embedding of early experience and its effects on health in adulthood. Ann N Y Acad Sci. 1999; 896, 85–95.Google Scholar
44. Kuzawa, CW, Sweet, E. Epigenetics and the embodiment of race: Developmental origins of US race disparities in cardiovascular health. Am J Hum Biol. 2009; 21, 2–15.Google Scholar
45. Lillycrop, KA, Slater-Jefferies, JL, Hanson, MA, et al. Induction of altered epigenetic regulation of the hepatic glucocorticoid receptor in the offspring of rats fed a protein-restricted diet during pregnancy suggests that reduced DNA methyltransferase-1 expression in involved in impaired DNA methylation and changes in histone modifications. Br J Nutr. 2007; 97, 1064–1073.Google Scholar
46. Thayer, ZM, Kuzawa, CW. Biological memories of past environments: epigenetic pathways to health disparities. Epigenetics. 2011; 6, 798–803.Google Scholar
47. Vaiserman, A. Epidemiologic evidence for association between adverse environmental exposures in early life and epigenetic variation: a potential link to disease susceptibility? Clin Epigenetics. 2015; 7, 96–106.Google Scholar
48. Wei, Y, Schatten, H, Sun, QY. Environmental epigenetic inheritance through gametes and implications for human reproduction. Hum Reprod Update. 2015; 21, 194–208.Google Scholar
49. Kertes, DA, Kamin, HS, Hughes, DA, et al. Prenatal maternal stress predicts methylation of genes regulating the hypothalamic-pituitary-adrenocortical system in mothers and newborns in the Democratic Republic of Congo. Child Dev. 2016; 87, 61–72.Google Scholar
50. Xu, L, Sun, Y, Gao, L, Cai, YY, Shi, SX. Prenatal restraint stress is associated with demethylation of corticotrophin releasing hormone (CRH) promoter and enhances CRH transcriptional responses to stress in adolescent rats. Neurochem Res. 2014; 39, 1193–1198.Google Scholar
51. Monk, M, Boubelik, M, Lehnert, S. Temporal and regional changes in DNA methylation in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development. 1987; 99, 371–382.Google Scholar
52. Reik, W. Stability and flexibility of epigenetic gene regulation in mammalian development. Nature. 2007; 447, 425–432.Google Scholar
53. Abdalla, H, Yoshizawa, Y, Hochi, S. Active demethylation of paternal genome in mammalian zygotes. J Reprod Dev. 2009; 55, 356–360.Google Scholar
54. Hales, BF, Grenier, L, Lalancette, C, Robaire, B. Epigenetic programming: from gametes to blastocyst. Birth Defects Res A Clin Mol Teratol. 2011; 91, 652–665.Google Scholar
55. Morgan, HD, Santos, F, Green, K, Dean, W, Reik, W. Epigenetic reprogramming in mammals. Hum Mol Genet. 2005; 14, R47–R58.Google Scholar
56. Yuen, RKC, Neumann, SMA, Fok, AK, et al. Extensive epigenetic reprogramming in human somatic tissues between fetus and adult. Epigenetics Chromatin. 2011; 4, 7–7.Google Scholar
57. Baird, DD, Weinberg, CR, Wilcox, AJ, McConnaughey, DR, Musey, PI. Using the ratio of urinary oestrogen and progesterone metabolites to estimate day of ovulation. Stat Med. 1991; 10, 255–266.Google Scholar
58. Kassam, A, Overstreet, JW, Snow-Harter, C, et al. Identification of anovulation and transient luteal function using a urinary pregnanediol-3-glucuronide ratio algorithm. Environ health Perspect. 1996; 104, 408–413.Google Scholar
59. O’Connor, KA, Brindle, E, Miller, RC, et al. Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierarchical method. Hum Reprod. 2006; 21, 1442–1452.Google Scholar
60. Nepomnaschy, PA, Weinberg, CR, Wilcox, AJ, Baird, DD. Urinary hCG patterns during the week following implantation. Hum Reprod. 2008; 23, 271–277.Google Scholar
61. Wilcox, AJ, Weinberg, CR, O’Connor, JF, et al. Incidence of early loss of pregnancy. N Engl J Med. 1988; 319, 189–194.Google Scholar
62. Nepomnaschy, PA, Altman, RM, Watterson, R, et al. Is cortisol excretion independent of menstrual cycle day? A longitudinal evaluation of first morning urinary specimens. PLoS One. 2011; 6, e18242.Google Scholar
63. Nepomnaschy, PA, Lee, TCK, Zeng, L, Dean, CB. Who is stressed? Methods to appropriately compare cortisol levels between individuals. Am J Hum Biol. 2012; 24, 515–525.Google Scholar
64. Gutteling, BM, de Weerth, C, Buitelaar, JK. Prenatal stress and children’s cortisol reaction to the first day of school. Psychoneuroendocrinology. 2005; 30, 541–549.Google Scholar
65. Buske-Kirschbaum, A, Jobst, S, Wustmans, A, et al. Attenuated free cortisol response to psychosocial stress in children with atopic dermatitis. Psychosom Med. 1997; 59, 419–426.Google Scholar
66. Dickerson, SS, Kemeny, ME. Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research. Psychol Bull. 2004; 130, 355–391.Google Scholar
67. Kudielka, BM, Buske-Kirschbaum, A, Hellhammer, DH, Kirschbaum, C. Differential heart rate reactivity and recovery after psychosocial stress (TSST) in healthy children, younger adults, and elderly adults: The impact of age and gender. Int J Behav Med. 2004; 11, 116–121.Google Scholar
68. Aardal-Eriksson, E, Karlberg, BE, Holm, A. Salivary cortisol – an alternative to serum cortisol determinations in dynamic function tests. Clin Chem Lab Med. 1998; 36, 215–222.Google Scholar
69. Kudielka, BM, Wust, S. Human models in acute and chronic stress: assessing determinants of individual hypothalamus-pituitary-adrenal axis activity and reactivity. Stress. 2010; 13, 1–14.Google Scholar
70. Salvante, KG, Brindle, E, McConnell, D, O’Connor, KA, Nepomnaschy, PA. Validation of a new multiplex assay against individual immunoassays for the quantification of reproductive, stress and energetic hormones in urine specimens. Am J Hum Biol. 2012; 24, 81–86.Google Scholar
71. O’Connor, KA, Brindle, E, Holman, DJ, et al. Urinary estrone conjugate and pregnanediol 3-glucuronide enzyme immunoassays for population research. Clin Chem. 2003; 49, 1139–1148.Google Scholar
72. Miller, RC, Brindle, E, Holman, DJ, et al. Comparison of specific gravity and creatinine for normalizing urinary reproductive hormone concentrations. Clin Chem. 2004; 50, 924–932.Google Scholar
73. White, BC, Jamison, KM, Grieb, C, et al. Specific gravity and creatinine as corrections for variation in urine concentration in humans, gorillas, and woolly monkeys. Am J Primatol. 2010; 72, 1082–1091.Google Scholar
74. Price, ME, Cotton, AM, Lam, LL, et al. Additional annotation enhances potential for biologically-relevant analysis of the Illumina Infinium HumanMethylation450 BeadChip array. Epigenetics Chromatin. 2013; 6, 4.Google Scholar
75. Maksimovic, J, Gordon, L, Oshlack, A. SWAN: Subset-quantile within array normalization for Illumina Infinium HumanMethylation450 BeadChips. Genome Biol. 2012; 13, R44.Google Scholar
76. Leek, JT, Johnson, WE, Parker, HS, Jaffe, AE, Storey, JD. The SVA package for removing batch effects and other unwanted variation in high-throughput experiments. Bioinformatics. 2012; 28, 882–883.Google Scholar
77. Farre, P, Jones, MJ, Meaney, MJ, et al. Concordant and discordant DNA methylation signatures of aging in human blood and brain. Epigenetics Chromatin. 2015; 8, 19.Google Scholar
78. Jones, MJ, Farre, P, McEwen, LM, et al. Distinct DNA methylation patterns of cognitive impairment and trisomy 21 in Down syndrome. BMC Med Genomics. 2013; 6, 58.Google Scholar
79. Keene, ON. The log transformation is special. Stat Med. 1995; 14, 811–819.Google Scholar
80. Aiken, LS, West, SG. Multiple Regression: Testing and Interpreting Interactions. 1991. Sage: Newbury Park.Google Scholar
81. Du, P, Zhang, X, Huang, CC, et al. Comparison of beta-value and M-value methods for quantifying methylation levels by microarray analysis. BMC Bioinformatics. 2010; 11, 587.Google Scholar
82. 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.Google Scholar
83. Kundakovic, M, Gudsnuk, K, Herbstman, JB, et al. DNA methylation of BDNF as a biomarker of early-life adversity. Proc Natl Acad Sci USA. 2015; 112, 6807–6813.Google Scholar
84. Heijmans, BT, Tobi, EW, Stein, AD, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci USA. 2008; 105, 17046–17049.Google Scholar
85. Binder, EB. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology. 2009; 34(Suppl 1), S186–S195.Google Scholar
86. Ziller, MJ, Gu, H, Muller, F, et al. Charting a dynamic DNA methylation landscape of the human genome. Nature. 2013; 500(7463), 477–481.Google Scholar
87. Varley, KE, Gertz, J, Bowling, KM, et al. Dynamic DNA methylation across diverse human cell lines and tissues. Genome Res. 2013; 23, 555–567.Google Scholar
88. Lam, LL, Emberly, E, Fraser, HB, et al. Factors underlying variable DNA methylation in a human community cohort. Proc Natl Acad Sci USA. 2012; 109(Suppl 2), 17253–17260.Google Scholar
89. Chadio, SE, Kotsampasi, B, Papadomichelakis, G, et al. Impact of maternal undernutrition on the hypothalamic-pituitary-adrenal axis responsiveness in sheep at different ages postnatal. J Endocrinol. 2007; 192, 495–503.Google Scholar
90. Hernandez, CE, Matthews, LR, Oliver, MH, Bloomfield, FH, Harding, JE. Effects of sex, litter size and peri-conceptional ewe nutrition on offspring behavioural and physiological response to isolation. Physiol Behav. 2010; 101, 588–594.Google Scholar
91. Zhang, S, Rattanatray, L, LacLaughlin, SM, et al. Peri-conceptional undernutrition in normal and overweight ewes leads to increased adrenal growth and epigenetic changes in adrenal IGF2/H19 gene in offspring. FASEB J. 2010; 24, 2772–2782.Google Scholar
92. Burkus, J, Kacmarova, M, Kubandova, J, et al. Stress exposure during the preimplantation period affects blastocyst lineages and offspring development. J Reprod Dev. 2015; 61, 325–331.Google Scholar
93. Zijlmans, MA, Riksen-Walraven, JM, de Weerth, C. Associations between maternal prenatal cortisol concentrations and child outcomes: a systematic review. Neurosci Biobehav Rev. 2015; 53, 1–24.Google Scholar
94. Martinez-Torteya, C, Bogat, GA, Levendosky, AA, von Eye, A. The influence of prenatal intimate partner violence exposure on hypothalamic-pituitary-adrenal axis reactivity and childhood internalizing and externalizing symptoms. Dev Psychopathol. 2016; 28, 55–72.Google Scholar
95. Sandman, CA, Glynn, LM, Davis, EP. Is there a viability-vulnerability tradeoff? Sex differences in fetal programming. J Psychosom Res. 2013; 75, 327–335.Google Scholar
96. Fernandez-Guasti, A, Fiedler, JL, Herrera, L, Handa, RJ. Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones. Horm Metab Res. 2012; 44, 607–618.Google Scholar
97. Richardson, HN, Zorrilla, EP, Mandyam, CD, Rivier, CL. Exposure to repetitive versus varied stress during prenatal development generates two distinct anxiogenic and neuroendocrine profiles in adulthood. Endocrinology. 2006; 147, 2506–2517.Google Scholar
98. Glover, V, Hill, J. Sex differences in the programming effects of prenatal stress on psychopathology and stress responses: an evolutionary perspective. Physiol Behav. 2012; 106, 736–740.Google Scholar
99. Chrousos, GP, Gold, PW. The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis. J Am Med Assoc. 1992; 267, 1244–1252.Google Scholar
100. Heim, C, Mletzko, T, Purselle, D, Musselman, DL, Nemeroff, CB. The dexamethasone/corticotropin-releasing factor test in men with major depression: role of childhood trauma. Biol Psychiatry. 2008; 63, 398–405.Google Scholar
101. Goldstein, JM, Handa, RJ, Tobet, SA. Disruption of fetal hormonal programming (prenatal stress) implicates shared risk for sex differences in depression and cardiovascular disease. Front Neuroendocrinol. 2014; 35, 140–158.Google Scholar
102. Brunton, PJ. Effects of maternal exposure to social stress during pregnancy: consequences for mother and offspring. Reproduction. 2013; 146, R175–R189.Google Scholar
103. Bartels, M, de Geus, EJ, Kirschbaum, C, Sluyter, F, Boomsma, DI. Heritability of daytime cortisol levels in children. Behav Genet. 2003; 33, 421–433.Google Scholar
104. Steptoe, A, van Jaarsveld, CH, Semmler, C, Plomin, R, Wardle, J. Heritability of daytime cortisol levels and cortisol reactivity in children. Psychoneuroendocrinology. 2009; 34, 273–280.Google Scholar
105. Van Hulle, CA, Shirtcliff, EA, Lemery-Chalfant, K, Goldsmith, HH. Genetic and environmental influences on individual differences in cortisol level and circadian rhythm in middle childhood. Horm Behav. 2012; 62, 36–42.Google Scholar
106. Zhang, S, Morrison, JL, Gill, A, et al. Maternal dietary restriction during the periconceptional period in normal-weight or obese ewes results in adrenocortical hypertrophy, an up-regulation of the JAK/STAT and down-regulation of the IGF1R signaling pathways in the adrenal of the postnatal lamb. Endocrinology. 2013; 154, 4650–4662.Google Scholar
107. Clemmons, DR. Insulin-like growth factor binding proteins and their role in controlling IGF actions. Cytokine Growth Factor Rev. 1997; 8, 45–62.Google Scholar
108. Kadakia, R, Josefson, J. The relationship of insulin-like growth factor 2 to fetal growth and adiposity. Horm Res Paediatr. 2016; 85, 75–82.Google Scholar
109. Laron, Z. Insulin-like growth factor 1 (IGF-1): a growth hormone. Mol Pathol. 2001; 54, 311–316.Google Scholar
110. Cohick, WS, Clemmons, DR. The insulin-like growth factors. Annu Rev Physiol. 1993; 55, 131–153.Google Scholar
111. Lewis, AJ, Austin, E, Galbally, M. Prenatal maternal mental health and fetal growth restriction: a systematic review. J Dev Orig Health Dis. 2016; 7, 416–428.Google Scholar
112. Alazard, R, Blaud, M, Elbaz, S, et al. Identification of the ‘NORE’ (N-Oct-3 responsive element), a novel structural motif and composite element. Nucleic Acids Res. 2005; 33, 1513–1523.Google Scholar
113. Ma, B, Wilker, EH, Willis-Owen, SA, et al. Predicting DNA methylation level across human tissues. Nucleic Acids Res. 2014; 42, 3515–3528.Google Scholar
114. Byun, HM, Siegmund, KD, Pan, F, et al. Epigenetic profiling of somatic tissues from human autopsy specimens identifies tissue- and individual-specific DNA methylation patterns. Hum Mol Genet. 2009; 18, 4808–4017.Google Scholar
115. Houtepen, LC, Vinkers, CH, Carrillo-Roa, T, et al. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nat Commun. 2016; 7, 10967.Google Scholar
116. Huang, YT, Chu, S, Loucks, EB, et al. Epigenome-wide profiling of DNA methylation in paired samples of adipose tissue and blood. Epigenetics. 2016; 11, 227–236.Google Scholar
117. Lokk, K, Modhukur, V, Rajashekar, B, et al. DNA methylome profiling of human tissues identifies global and tissue-specific methylation patterns. Genome Biol. 2014; 15, r54.Google Scholar
118. Black, S, Devereux, P, Salvanes, K. Why the Apple doesn’t fall far: understanding intergenerational transmission of human capital. Am Econ Rev. 2005; 95, 437–449.Google Scholar
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