Skip to main content
SpringerLink
Log in

Epigenetic Effects of Prenatal Stress

  • Chapter
  • First Online:
Prenatal Stress and Child Development

Abstract

Biological embedding of prenatal stress can increase the risk for maladaptive child neurodevelopmental outcomes. The search is on for more precise mechanisms implicated in this biological embedding. In recent years, researchers have focused on how epigenetic processes are implicated in the transmission of prenatal stress to the fetus. A number of specific epigenetic mechanisms have been studied to test the hypothesis that prenatal stress signals may alter epigenetic processes and, subsequently, fetal stress response systems. In this chapter, we briefly discuss the historical, theoretical, and empirical background linking epigenetic mechanisms with prenatal stress research. We describe common epigenetic mechanisms and the promises as well as difficulties inherent in examining epigenetic processes as mechanisms linking prenatal stress with child developmental outcomes in humans. As an example of our approach to examining these epigenetic processes, we review key genes that are implicated in the fetal programming of the stress response that could have downstream effects on immune system functioning and neurodevelopment. Finally, we discuss future directions for the study of epigenetic processes linking maternal prenatal stress with offspring neurodevelopmental outcomes.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 199.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abbott, P. W., Gumusoglu, S. B., Bittle, J., Beversdorf, D. Q., & Stevens, H. E. (2018). Prenatal stress and genetic risk: How prenatal stress interacts with genetics to alter risk for psychiatric illness. Psychoneuroendocrinology, 90, 9–21.

    Article  Google Scholar 

  • Adalsteinsson, B., & Ferguson-Smith, A. (2014). Epigenetic control of the genome—Lessons from genomic imprinting. Genes, 5(3), 635–655.

    Article  Google Scholar 

  • Almond, D., & Currie, J. (2011). Killing me softly: The fetal origins hypothesis. Journal of Economic Perspectives, 25(3), 153–172.

    Article  Google Scholar 

  • Appleton, A. A., Armstrong, D. A., Lesseur, C., Lee, J., Padbury, J. F., Lester, B. M., & Marsit, C. J. (2013). Patterning in placental 11-B hydroxysteroid dehydrogenase methylation according to prenatal socioeconomic adversity. PLoS One, 8, 1–7.

    Article  Google Scholar 

  • Apter-Levy, Y., Feldman, M., Vakart, A., Ebstein, R. P., & Feldman, R. (2013). Impact of maternal depression across the first 6 years of life on the child’s mental health, social engagement, and empathy: The moderating role of oxytocin. American Journal of Psychiatry, 170(10), 1161–1168.

    Article  Google Scholar 

  • Bannister, A. J., & Kouzarides, T. (2011). Regulation of chromatin by histone modifications. Cell Research, 21(3), 381.

    Article  Google Scholar 

  • Barker, D. J. (2007). The origins of the developmental origins theory. Journal of Internal Medicine, 261, 412–417.

    Article  Google Scholar 

  • Barker, D. J., Osmond, C., Winter, P. D., Margetts, B., & Simmonds, S. J. (1989). Weight in infancy and death from ischaemic heart disease. The Lancet, 334, 577–580.

    Article  Google Scholar 

  • Baron, U., Floess, S., Wieczorek, G., Baumann, K., Grützkau, A., Dong, J., et al. (2007). DNA demethylation in the human FOXP3 locus discriminates regulatory T cells from activated FOXP3+ conventional T cells. European Journal of Immunology, 37(9), 2378–2389.

    Article  Google Scholar 

  • Bateson, P., Gluckman, P., & Hanson, M. (2014). The biology of developmental plasticity and the predictive adaptive response hypothesis. The Journal of Physiology, 592(11), 2357–2368.

    Article  Google Scholar 

  • Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummett, B., & Williams, R. (2009). Vulnerability genes or plasticity genes? Molecular Psychiatry, 14(8), 746.

    Article  Google Scholar 

  • Betts, K. S., Williams, G. M., Najman, J. M., & Alati, R. (2015). The relationship between maternal depressive, anxious, and stress symptoms during pregnancy and adult offspring behavioral and emotional problems. Depression and Anxiety, 32(2), 82–90.

    Article  Google Scholar 

  • Bird, A. (2007). Perceptions of epigenetics. Nature, 447(7143), 396.

    Article  Google Scholar 

  • Boyce, W. T., & Kobor, M. S. (2015). Development and the epigenome: The ‘synapse’ of gene–environment interplay. Developmental Science, 18(1), 1–23.

    Article  Google Scholar 

  • Braithwaite, E. C., Kundakovic, M., Ramchandani, P. G., Murphy, S. E., & Champagne, F. A. (2015). Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation. Epigenetics, 10(5), 408–417.

    Article  Google Scholar 

  • Branchi, I., & Cirulli, F. (2014). Early experiences: Building up the tools to face the challenges of adult life. Developmental Psychobiology, 56(8), 1661–1674.

    Article  Google Scholar 

  • Brown, A. S., Hooton, J., Schaefer, C. A., Zhang, H., Petkova, E., Babulas, V., et al. (2004). Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. American Journal of Psychiatry, 161(5), 889–895.

    Article  Google Scholar 

  • Buka, S. L., Tsuang, M. T., Torrey, E. F., Klebanoff, M. A., Bernstein, D., & Yolken, R. H. (2001). Maternal infections and subsequent psychosis among offspring. Archives of General Psychiatry, 58(11), 1032–1037.

    Article  Google Scholar 

  • Cao-Lei, L., Massart, R., Suderman, M. J., Machnes, Z., Elgbeili, G., Laplante, D. P., et al. (2014). DNA methylation signatures triggered by prenatal maternal stress exposure to a natural disaster: Project ice storm. PLoS One, 9(9), e107653.

    Article  Google Scholar 

  • Cao-Lei, L., Elgbeili, G., Massart, R., Laplante, D. P., Szyf, M., & King, S. (2015). Pregnant women’s cognitive appraisal of a natural disaster affects DNA methylation in their children 13 years later: Project ice storm. Translational Psychiatry, 5(2), e515.

    Article  Google Scholar 

  • Cao-Lei, L., Laplante, D. P., & King, S. (2016a). Prenatal maternal stress and epigenetics: Review of the human research. Current Molecular Biology Reports, 2(1), 16–25.

    Article  Google Scholar 

  • Cao-Lei, L., Veru, F., Elgbeili, G., Szyf, M., Laplante, D. P., & King, S. (2016b). DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13½ years: Project ice storm. Clinical Epigenetics, 8(1), 54.

    Article  Google Scholar 

  • Capron, L. E., Ramchandani, P. G., & Glover, V. (2018). Maternal prenatal stress and placental gene expression of NR3C1 and HSD11B2: The effects of maternal ethnicity. Psychoneuroendocrinology, 87, 166–172.

    Article  Google Scholar 

  • Champagne, D. L., de Kloet, E. R., & Joëls, M. (2009, June). Fundamental aspects of the impact of glucocorticoids on the (immature) brain. In Seminars in fetal and neonatal medicine (Vol. 14, No. 3, pp. 136–142). WB Saunders.

    Google Scholar 

  • Chuang, J. C., & Jones, P. A. (2007). Epigenetics and microRNAs. Pediatric Research, 61(5 Part 2), 24R.

    Article  Google Scholar 

  • Comasco, E., Ã…slund, C., Oreland, L., & Nilsson, K. W. (2013). Three-way interaction effect of 5-HTTLPR, BDNF Val66Met, and childhood adversity on depression: A replication study. European Neuropsychopharmacology, 23(10), 1300–1306.

    Article  Google Scholar 

  • Conradt, E., Lester, B. M., Appleton, A. A., Armstrong, D. A., & Marsit, C. J. (2013). The roles of DNA methylation of NR3C1 and 11β-HSD2 and exposure to maternal mood disorder in utero on newborn neuro- behavior. Epigenetics, 8, 1321–1329.

    Article  Google Scholar 

  • Conradt, E., Hawes, K., Guerin, D., Armstrong, D. A., Marsit, C. J., Tronick, E., & Lester, B. M. (2016). The contributions of maternal sensitivity and maternal depressive symptoms to epigenetic processes and neuroendocrine functioning. Child Development, 87(1), 73–85.

    Article  Google Scholar 

  • Coussons-Read, M. E., Okun, M. L., Schmitt, M. P., & Giese, S. (2005). Prenatal stress alters cytokine levels in a manner that may endanger human pregnancy. Psychosomatic Medicine, 67(4), 625–631.

    Article  Google Scholar 

  • Coussons-Read, M. E., Okun, M. L., & Nettles, C. D. (2007). Psychosocial stress increases inflammatory markers and alters cytokine production across pregnancy. Brain, Behavior, and Immunity, 21(3), 343–350.

    Article  Google Scholar 

  • De Kloet, E. R., Joëls, M., & Holsboer, F. (2005). Stress and the brain: From adaptation to disease. Nature Reviews Neuroscience, 6(6), 463.

    Article  Google Scholar 

  • De Weerth, C. (2018). Prenatal stress and the development of psychopathology: Lifestyle behaviors as a fundamental part of the puzzle. Development and Psychopathology, 30(3), 1129–1144.

    Article  Google Scholar 

  • Devlin, A. M., Brain, U., Austin, J., & Oberlander, T. F. (2010). Prenatal exposure to maternal depressed mood and the MTHFR C677T variant affect SLC6A4 methylation in infants at birth. PLoS One, 5(8), e12201.

    Article  Google Scholar 

  • Doyle, C., & Cicchetti, D. (2018). Future directions in prenatal stress research: Challenges and opportunities related to advancing our understanding of prenatal developmental origins of risk for psychopathology. Development and Psychopathology, 30(3), 721–724.

    Article  Google Scholar 

  • Dukal, H., Frank, J., Lang, M., Treutlein, J., Gilles, M., Wolf, I. A., et al. (2015). New-born females show higher stress-and genotype-independent methylation of SLC6A4 than males. Borderline personality disorder and emotion dysregulation, 2(1), 8.

    Article  Google Scholar 

  • Ellis, B. J., Boyce, W. T., Belsky, J., Bakermans-Kranenburg, M. J., & Van IJzendoorn, M. H. (2011). Differential susceptibility to the environment: An evolutionary–neurodevelopmental theory. Development and Psychopathology, 23(1), 7–28.

    Article  Google Scholar 

  • Entringer, S., Kumsta, R., Nelson, E. L., Hellhammer, D. H., Wadhwa, P. D., & Wüst, S. (2008a). Influence of prenatal psychosocial stress on cytokine production in adult women. Developmental Psychobiology: The Journal of the International Society for Developmental Psychobiology, 50(6), 579–587.

    Article  Google Scholar 

  • Entringer, S., Wüst, S., Kumsta, R., Layes, I. M., Nelson, E. L., Hellhammer, D. H., & Wadhwa, P. D. (2008b). Prenatal psychosocial stress exposure is associated with insulin resistance in young adults. American Journal of Obstetrics and Gynecology, 199(5), 498–4e1.

    Article  Google Scholar 

  • Entringer, S., Kumsta, R., Hellhammer, D. H., Wadhwa, P. D., & Wüst, S. (2009). Prenatal exposure to maternal psychosocial stress and HPA axis regulation in young adults. Hormones and Behavior, 55(2), 292–298.

    Article  Google Scholar 

  • Entringer, S., Epel, E. S., Kumsta, R., Lin, J., Hellhammer, D. H., Blackburn, E. H., et al. (2011). Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood. Proceedings of the National Academy of Sciences, 108(33), E513–E518.

    Article  Google Scholar 

  • Eriksson, J. G., Sandboge, S., Salonen, M. K., Kajantie, E., & Osmond, C. (2014). Long-term consequences of maternal overweight in pregnancy on offspring later health: Findings from the Helsinki birth cohort study. Annals of Medicine, 46(6), 434–438.

    Article  Google Scholar 

  • Fatemi, S. H., Reutiman, T. J., Folsom, T. D., Huang, H., Oishi, K., Mori, S., et al. (2008). Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: Implications for genesis of neurodevelopmental disorders. Schizophrenia Research, 99(1–3), 56–70.

    Article  Google Scholar 

  • Forsen, T., Eriksson, J. G., Tuomilehto, J., Teramo, K., Osmond, C., & Barker, D. J. P. (1997). Mother’s weight in pregnancy and coronary heart disease in a cohort of Finnish men: Follow up study. BMJ, 315(7112), 837–840.

    Article  Google Scholar 

  • Frankel, S., Elwood, P., Smith, G. D., Sweetnam, P., & Yarnell, J. (1996). Birthweight, body-mass index in middle age, and incident coronary heart disease. The Lancet, 348(9040), 1478–1480.

    Article  Google Scholar 

  • Franzen, P. L., & Buysse, D. J. (2008). Sleep disturbances and depression: Risk relationships for subsequent depression and therapeutic implications. Dialogues in Clinical Neuroscience, 10(4), 473.

    Article  Google Scholar 

  • Graignic-Philippe, R., Dayan, J., Chokron, S., Jacquet, A. Y., & Tordjman, S. (2014). Effects of prenatal stress on fetal and child development: A critical literature review. Neuroscience and Biobehavioral Reviews, 43, 137–162.

    Article  Google Scholar 

  • Gray, S. M., Kaech, S. M., & Staron, M. M. (2014). The interface between transcriptional and epigenetic control of effector and memory CD 8+ T-cell differentiation. Immunological Reviews, 261(1), 157–168.

    Article  Google Scholar 

  • Greally, J. M. (2018). A user’s guide to the ambiguous word ‘epigenetics’. Nature Reviews. Molecular Cell Biology, 19(4), 207–208.

    Article  Google Scholar 

  • Hamada, K., Suzaki, Y., Goldman, A., Ning, Y. Y., Goldsmith, C., Palecanda, A., et al. (2003). Allergen-independent maternal transmission of asthma susceptibility. The Journal of Immunology, 170(4), 1683–1689.

    Article  Google Scholar 

  • Hartnett, L., & Egan, L. J. (2012). Inflammation, DNA methylation and colitis-associated cancer. Carcinogenesis, 33(4), 723–731.

    Article  Google Scholar 

  • Henikoff, S., & Greally, J. M. (2016). Epigenetics, cellular memory and gene regulation. Current Biology, 26(14), R644–R648.

    Article  Google Scholar 

  • Hill, J., Pickles, A., Wright, N., Braithwaite, E., & Sharp, H. (2019). Predictions of children’s emotionality from evolutionary and epigenetic hypotheses. Scientific Reports, 9, 1), 1–1),11.

    Article  Google Scholar 

  • Holloway, T., Moreno, J. L., Umali, A., Rayannavar, V., Hodes, G. E., Russo, S. J., & González-Maeso, J. (2013). Prenatal stress induces schizophrenia-like alterations of serotonin 2A and metabotropic glutamate 2 receptors in the adult offspring: Role of maternal immune system. Journal of Neuroscience, 33(3), 1088–1098.

    Article  Google Scholar 

  • Hompes, T., Izzi, B., Gellens, E., Morreels, M., Fieuws, S., Pexsters, A., et al. (2013). Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood. Journal of Psychiatric Research, 47(7), 880–891.

    Article  Google Scholar 

  • Howerton, C. L., & Bale, T. L. (2012). Prenatal programing: At the intersection of maternal stress and immune activation. Hormones and Behavior, 62(3), 237–242.

    Article  Google Scholar 

  • Kagan, J. (2016). An overly permissive extension. Perspectives on Psychological Science, 11(4), 442–450.

    Article  Google Scholar 

  • Kertes, D. A., Kamin, H. S., Hughes, D. A., Rodney, N. C., Bhatt, S., & Mulligan, C. J. (2016). Prenatal maternal stress predicts methylation of genes regulating the hypothalamic–pituitary–adrenocortical system in mothers and newborns in the Democratic Republic of Congo. Child Development, 87(1), 61–72.

    Article  Google Scholar 

  • King, S., Mancini-Marïe, A., Brunet, A., Walker, E., Meaney, M. J., & Laplante, D. P. (2009). Prenatal maternal stress from a natural disaster predicts dermatoglyphic asymmetry in humans. Development and Psychopathology, 21(2), 343–353.

    Article  Google Scholar 

  • King, S., Dancause, K., Turcotte-Tremblay, A. M., Veru, F., & Laplante, D. P. (2012). Using natural disasters to study the effects of prenatal maternal stress on child health and development. Birth Defects Research Part C: Embryo Today: Reviews, 96(4), 273–288.

    Article  Google Scholar 

  • Knight, A. K., Craig, J. M., Theda, C., Bækvad-Hansen, M., Bybjerg-Grauholm, J., Hansen, C. S., et al. (2016). An epigenetic clock for gestational age at birth based on blood methylation data. Genome Biology, 17(1), 206.

    Article  Google Scholar 

  • Koukoura, O., Sifakis, S., & Spandidos, D. A. (2012). DNA methylation in the human placenta and fetal growth. Molecular Medicine Reports, 5(4), 883–889.

    Article  Google Scholar 

  • Lai, A. Y., Mav, D., Shah, R., Grimm, S. A., Phadke, D., Hatzi, K., et al. (2013). DNA methylation profiling in human B cells reveals immune regulatory elements and epigenetic plasticity at Alu elements during B-cell activation. Genome Research, 23(12), 2030–2041.

    Article  Google Scholar 

  • Laplante, D. P., Brunet, A., Schmitz, N., Ciampi, A., & King, S. (2008). Project ice storm: Prenatal maternal stress affects cognitive and linguistic functioning in 5½-year-old children. Journal of the American Academy of Child & Adolescent Psychiatry, 47(9), 1063–1072.

    Article  Google Scholar 

  • Lappalainen, T., & Greally, J. M. (2017). Associating cellular epigenetic models with human phenotypes. Nature Reviews Genetics, 18(7), 441.

    Article  Google Scholar 

  • Lemaire, V., Lamarque, S., Le Moal, M., Piazza, P. V., & Abrous, D. N. (2006). Postnatal stimulation of the pups counteracts prenatal stress-induced deficits in hippocampal neurogenesis. Biological Psychiatry, 59(9), 786–792.

    Article  Google Scholar 

  • Leon, D. A., Lithell, H. O., VÃ¥gerö, D., Koupilová, I., Mohsen, R., Berglund, L., et al. (1998). Reduced fetal growth rate and increased risk of death from ischaemic heart disease: Cohort study of 15 000 Swedish men and women born 1915-29. BMJ, 317(7153), 241–245.

    Article  Google Scholar 

  • Lester, B. M., Tronick, E., Nestler, E., Abel, T., Kosofsky, B., Kuzawa, C. W.,... & Reul, J. M. (2011). Behavioral epigenetics. Annals of the New York Academy of Sciences, 1226, 14.

    Google Scholar 

  • Li, Q., & Verma, I. M. (2002). NF-κB regulation in the immune system. Nature Reviews Immunology, 2(10), 725–734.

    Article  Google Scholar 

  • Lim, D. H. K., & Maher, E. R. (2010). DNA methylation: A form of epigenetic control of gene expression. The Obstetrician & Gynecologist, 12, 37–42.

    Article  Google Scholar 

  • Littleton, H. L., Bye, K., Buck, K., & Amacker, A. (2010). Psychosocial stress during pregnancy and perinatal outcomes: A meta-analytic review. Journal of Psychosomatic Obstetrics and Gynecology, 31(4), 219–228.

    Article  Google Scholar 

  • Liu, Y., Murphy, S. K., Murtha, A. P., Fuemmeler, B. F., Schildkraut, J., Huang, Z., et al. (2012). Depression in pregnancy, infant birth weight and DNA methylation of imprint regulatory elements. Epigenetics, 7(7), 735–746.

    Article  Google Scholar 

  • Maekita, T., Nakazawa, K., Mihara, M., Nakajima, T., Yanaoka, K., Iguchi, M., et al. (2006). High levels of aberrant DNA methylation in helicobacter pylori–infected gastric mucosae and its possible association with gastric cancer risk. Clinical Cancer Research, 12(3), 989–995.

    Article  Google Scholar 

  • Mansell, T., Novakovic, B., Meyer, B., Rzehak, P., Vuillermin, P., Ponsonby, A. L., et al. (2016). The effects of maternal anxiety during pregnancy on IGF2/H19 methylation in cord blood. Translational Psychiatry, 6(3), e765.

    Article  Google Scholar 

  • Marsit, C. J., Maccani, M. A., Padbury, J. F., & Lester, B. M. (2012). Placental 11- beta hydroxysteroid dehydrogenase methylation is associated with newborn growth and a measure of neurobehavioral outcome. PLoS One, 7, 1–9.

    Article  Google Scholar 

  • Martino, D., & Prescott, S. (2011). Epigenetics and prenatal influences on asthma and allergic airways disease. Chest, 139(3), 640–647.

    Article  Google Scholar 

  • Martino, D. J., & Prescott, S. L. (2013). Progress in understanding the epigenetic basis for immune development, immune function, and the rising incidence of allergic disease. Current Allergy and Asthma Reports, 13(1), 85–92.

    Article  Google Scholar 

  • Monk, C., Spicer, J., & Champagne, F. A. (2012). Linking prenatal maternal adversity to developmental outcomes in infants: The role of epigenetic pathways. Development and Psychopathology, 24, 1361–1376. https://doi.org/10.1017/S0954579412000764.

    Article  Google Scholar 

  • Monk, C., Feng, T., Lee, S., Krupska, I., Champagne, F. A., & Tycko, B. (2016). Distress during pregnancy: Epigenetic regulation of placenta glucocorticoid-related genes and fetal neurobehavior. The American Journal of Psychiatry, 7, 705–713.

    Article  Google Scholar 

  • Morales-Nebreda, L., McLafferty, F. S., & Singer, B. D. (2018). DNA methylation as a transcriptional regulator of the immune system. Translational Research, 204, 1–18.

    Article  Google Scholar 

  • Moutinho, C., & Esteller, M. (2017). MicroRNAs and epigenetics. In Advances in cancer research (Vol. 135, pp. 189–220). Academic.

    Google Scholar 

  • Mulligan, C., D’Errico, N., Stees, J., & Hughes, D. (2012). Methylation changes at NR3C1 in newborns associate with maternal prenatal stress exposure and newborn birth weight. Epigenetics, 7(8), 853–857.

    Article  Google Scholar 

  • Murgatroyd, C., Quinn, J. P., Sharp, H. M., Pickles, A., & Hill, J. (2015). Effects of prenatal and postnatal depression, and maternal stroking, at the glucocorticoid receptor gene. Translational Psychiatry, 5, 1–5.

    Article  Google Scholar 

  • Murphy, S. K., Huang, Z., & Hoyo, C. (2012). Differentially methylated regions of imprinted genes in prenatal, perinatal and postnatal human tissues. PLoS One, 7(7), e40924.

    Article  Google Scholar 

  • Nederhof, E., & Schmidt, M. V. (2012). Mismatch or cumulative stress: Toward an integrated hypothesis of programming effects. Physiology & Behavior, 106(5), 691–700.

    Article  Google Scholar 

  • Nieratschker, V., Massart, R., Gilles, M., Luoni, A., Suderman, M. J., Krumm, B., et al. (2014). MORC1 exhibits cross-species differential methylation in association with early life stress as well as genome-wide association with MDD. Translational Psychiatry, 4(8), e429.

    Article  Google Scholar 

  • Non, A. L., Binder, A. M., Kubzansky, L. D., & Michels, K. B. (2014). Genome-wide DNA methylation in neonates exposed to maternal depression, anxiety, or SSRI medication during pregnancy. Epigenetics, 9(7), 964–972.

    Article  Google Scholar 

  • Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008). Prenatal exposure to maternal depression, neonatal methylation of human glucocorticoid receptor gene (NR3C1) and infant cortisol stress responses. Epigenetics, 3, 97–106.

    Article  Google Scholar 

  • Ostlund, B. D., Conradt, E., Crowell, S. E., Tyrka, A. R., Marsit, C. J., & Lester, B. M. (2016). Prenatal stress, fearfulness, and the epigenome: Exploratory analysis of sex differences in DNA methylation of the glucocorticoid receptor gene. Frontiers in Behavioral Neuroscience, 10, 1–8.

    Article  Google Scholar 

  • Petronis, A. (2010). Epigenetics as a unifying principle in the aetiology of complex traits and diseases. Nature, 465(7299), 721.

    Article  Google Scholar 

  • Pincus-Knackstedt, M. K., Joachim, R. A., Blois, S. M., Douglas, A. J., Orsal, A. S., Klapp, B. F., et al. (2006). Prenatal stress enhances susceptibility of murine adult offspring toward airway inflammation. The Journal of Immunology, 177(12), 8484–8492.

    Article  Google Scholar 

  • Prescott, S. L., Taylor, A., Roper, J., Wahdan, A., Noakes, P., Thornton, C., et al. (2005). Maternal reactivity to fetal alloantigens is related to newborn immune responses and subsequent allergic disease. Clinical & Experimental Allergy, 35(4), 417–425.

    Article  Google Scholar 

  • Reynolds, R. M., Allan, K. M., Raja, E. A., Bhattacharya, S., McNeill, G., Hannaford, P. C., et al. (2013). Maternal obesity during pregnancy and premature mortality from cardiovascular event in adult offspring: Follow-up of 1 323 275 person years. BMJ, 347, f4539.

    Article  Google Scholar 

  • Richardson, B. (2003). DNA methylation and autoimmune disease. Clinical Immunology, 109(1), 72–79.

    Article  Google Scholar 

  • Rich-Edwards, J. W., Stampfer, M. J., Manson, J. E., Rosner, B., Hankinson, S. E., Colditz, G. A., et al. (1997). Birth weight and risk of cardiovascular disease in a cohort of women followed up since 1976. BMJ, 315(7105), 396–400.

    Article  Google Scholar 

  • Richetto, J., Massart, R., Weber-Stadlbauer, U., Szyf, M., Riva, M. A., & Meyer, U. (2017). Genome-wide DNA methylation changes in a mouse model of infection-mediated neurodevelopmental disorders. Biological Psychiatry, 81(3), 265–276.

    Article  Google Scholar 

  • Rijlaarsdam, J., Pappa, I., Walton, E., Bakermans-Kranenburg, M. J., Mileva-Seitz, V. R., Rippe, R. C., et al. (2016). An epigenome-wide association meta-analysis of prenatal maternal stress in neonates: A model approach for replication. Epigenetics, 11(2), 140–149.

    Article  Google Scholar 

  • Rodney, N. C., & Mulligan, C. J. (2014). A biocultural study of the effects of maternal stress on mother and newborn health in the Democratic Republic of Congo. American Journal of Physical Anthropology, 155(2), 200–209.

    Article  Google Scholar 

  • Ross, K. M., Cole, S. W., Carroll, J. E., & Schetter, C. D. (2019). Elevated pro-inflammatory gene expression in the third trimester of pregnancy in mothers who experienced stressful life events. Brain, Behavior, and Immunity, 76, 97–103.

    Article  Google Scholar 

  • Santarelli, S., Zimmermann, C., Kalideris, G., Lesuis, S. L., Arloth, J., Uribe, A., et al. (2017). An adverse early life environment can enhance stress resilience in adulthood. Psychoneuroendocrinology, 78, 213–221.

    Article  Google Scholar 

  • Scharer, C. D., Barwick, B. G., Youngblood, B. A., Ahmed, R., & Boss, J. M. (2013). Global DNA methylation remodeling accompanies CD8 T cell effector function. The Journal of Immunology, 191(6), 3419–3429.

    Article  Google Scholar 

  • Scheuer, S., Ising, M., Uhr, M., Otto, Y., von Klitzing, K., & Klein, A. M. (2016). FKBP5 polymorphisms moderate the influence of adverse life events on the risk of anxiety and depressive disorders in preschool children. Journal of Psychiatric Research, 72, 30–36.

    Article  Google Scholar 

  • Schmidt, M. V. (2011). Animal models for depression and the mismatch hypothesis of disease. Psychoneuroendocrinology, 36(3), 330–338.

    Article  Google Scholar 

  • Schroeder, J. W., Smith, A. K., Brennan, P. A., Conneely, K. N., Kilaru, V., Knight, B. T., et al. (2012). DNA methylation in neonates born to women receiving psychiatric care. Epigenetics, 7(4), 409–414.

    Article  Google Scholar 

  • Serpeloni, F., Radtke, K. M., Hecker, T., Sill, J., Vukojevic, V., Assis, S. G. D., et al. (2019). Does prenatal stress shape postnatal resilience?–an epigenome-wide study on violence and mental health in humans. Frontiers in Genetics, 10, 269.

    Article  Google Scholar 

  • Sosnowski, D. W., Booth, C., York, T. P., Amstadter, A. B., & Kliewer, W. (2018). Maternal prenatal stress and infant DNA methylation: A systematic review. Developmental Psychobiology, 60(2), 127–139.

    Article  Google Scholar 

  • Stein, C. E., Fall, C. H. D., Kumaran, K., Osmond, C., Barker, D. J. P., & Cox, V. (1996). Fetal growth and coronary heart disease in South India. The Lancet, 348(9037), 1269–1273.

    Article  Google Scholar 

  • Stroud, L. R., Papandonatos, G. D., Parade, S. H., Salisbury, A. L., Phipps, M. G., Lester, B. M., et al. (2016). Prenatal major depressive disorder, placenta glucocorticoid and serotonergic signaling, and infant cortisol response. Psychosomatic Medicine, 78, 979–990.

    Article  Google Scholar 

  • Suarez, A., Lahti, J., Czamara, D., Lahti-Pulkkinen, M., Knight, A. K., Girchenko, P., et al. (2018). The epigenetic clock at birth: Associations with maternal antenatal depression and child psychiatric problems. Journal of the American Academy of Child & Adolescent Psychiatry, 57(5), 321–328.

    Article  Google Scholar 

  • Sun, L., & Sun, S. (2019). Within-sample co-methylation patterns in normal tissues. BioData Mining, 12(1), 9.

    Article  Google Scholar 

  • Torche, F., & Kleinhaus, K. (2012). Prenatal stress, gestational age and secondary sex ratio: The sex-specific effects of exposure to a natural disaster in early pregnancy. Human Reproduction, 27(2), 558–567.

    Article  Google Scholar 

  • Tsuno, N., Besset, A., & Ritchie, K. (2005). Sleep and depression. The Journal of Clinical Psychiatry, 66(10), 1254.

    Article  Google Scholar 

  • Unternaehrer, E., Bolten, M., Nast, I., Staehli, S., Meyer, A. H., Dempster, E., et al. (2016). Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation. Social Cognitive and Affective Neuroscience, 11(9), 1460–1470.

    Article  Google Scholar 

  • Vaiserman, A. M., & Koliada, A. K. (2017). Early-life adversity and long-term neurobehavioral outcomes: Epigenome as a bridge? Human Genomics, 11(1), 34.

    Article  Google Scholar 

  • Vangeel, E. B., Izzi, B., Hompes, T., Vansteelandt, K., Lambrechts, D., Freson, K., & Claes, S. (2015). DNA methylation in imprinted genes IGF2 and GNASXL is associated with prenatal maternal stress. Genes, Brain and Behavior, 14(8), 573–582.

    Article  Google Scholar 

  • Vidal, A. C., Neelon, S. E. B., Liu, Y., Tuli, A. M., Fuemmeler, B. F., Hoyo, C., et al. (2014). Maternal stress, preterm birth, and DNA methylation at imprint regulatory sequences in humans. Genetics & Epigenetics, 6, GEG-S18067.

    Article  Google Scholar 

  • Virgin, C. E., Jr., Ha, T. P. T., Packan, D. R., Tombaugh, G. C., Yang, S. H., Homer, H. C., & Sapolsky, R. M. (1991). Glucocorticoids inhibit glucose transport and glutamate uptake in hippocampal astrocytes: Implications for glucocorticoid neurotoxicity. Journal of Neurochemistry, 57(4), 1422–1428.

    Article  Google Scholar 

  • Von Hertzen, L. C. (2002). Maternal stress and T-cell differentiation of the developing immune system: Possible implications for the development of asthma and atopy. Journal of Allergy and Clinical Immunology, 109(6), 923–928.

    Article  Google Scholar 

  • Weaver, I. C., Cervoni, N., Champagne, F. A., D’Alessio, A. C., Sharma, S., Seckl, J. R., et al. (2004). Epigenetic programming by maternal behavior. Nature Neuroscience, 7(8), 847–854.

    Article  Google Scholar 

  • Zbozinek, T. D., Rose, R. D., Wolitzky-Taylor, K. B., Sherbourne, C., Sullivan, G., Stein, M. B., et al. (2012). Diagnostic overlap of generalized anxiety disorder and major depressive disorder in a primary care sample. Depression and Anxiety, 29(12), 1065–1071.

    Article  Google Scholar 

  • Zhang, B., Zhou, Y., Lin, N., Lowdon, R. F., Hong, C., Nagarajan, R. P., et al. (2013). Functional DNA methylation differences between tissues, cell types, and across individuals discovered using the M&M algorithm. Genome Research, 23(9), 1522–1540.

    Article  Google Scholar 

  • Zhang, W., Ham, J., Li, Q., Deyssenroth, M. A., Lambertini, L., Huang, Y., et al. (2020). Moderate prenatal stress may buffer the impact of superstorm Sandy on placental genes: Stress in pregnancy (SIP) study. PLoS One, 15(1), e0226605.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Developmental Brain Science Program, University of Massachusetts, Boston, MA, USA

    Isabelle Mueller

  2. Department of Psychology, University of Utah, Salt Lake City, UT, USA

    Nila Shakiba

  3. Departments of Psychology, Psychiatry, and Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA

    Mindy A. Brown & Sheila E. Crowel

  4. Departments of Psychology, Obstetrics and Gynecology, and Pediatrics, University of Utah, Salt Lake City, UT, USA

    Elisabeth Conradt

Authors
  1. Isabelle Mueller
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nila Shakiba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mindy A. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sheila E. Crowel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Elisabeth Conradt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Elisabeth Conradt .

Editor information

Editors and Affiliations

  1. Department of Psychiatry, McGill University, Montreal, QC, Canada

    Ashley Wazana  & Eszter Székely  & 

  2. Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada

    Ashley Wazana  & Eszter Székely  & 

  3. BC Children‘s Hospital, BC Women‘s Hospital and Health Centre, Vancouver, BC, Canada

    Tim F. Oberlander

  4. Department of Pediatrics Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Tim F. Oberlander

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Mueller, I., Shakiba, N., Brown, M.A., Crowel, S.E., Conradt, E. (2021). Epigenetic Effects of Prenatal Stress. In: Wazana, A., Székely, E., Oberlander, T.F. (eds) Prenatal Stress and Child Development. Springer, Cham. https://doi.org/10.1007/978-3-030-60159-1_5

Download citation

Publish with us

Policies and ethics

Search

Navigation