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Maternal psychosocial stress during pregnancy alters the epigenetic signature of the glucocorticoid receptor gene promoter in their offspring: a meta-analysis
Open accessAbstract
Prenatal stress has been widely associated with a number of short- and long-term pathological outcomes. Epigenetic mechanisms are thought to partially mediate these environmental insults into the fetal physiology. One of the main targets of developmental programming is the hypothalamic-pituitary-adrenal (HPA) axis as it is the main regulator of the stress response. Accordingly, an increasing number of researchers have recently focused on the putative association between DNA methylation at the glucocorticoid receptor gene (NR3C1) and prenatal stress, among other types of psychosocial stress. The current study aims to systematically review and meta-analyze the existing evidence linking several forms of prenatal stress with DNA methylation at the region 1F of the NR3C1 gene. The inclusion of relevant articles allowed combining empirical evidence from 977 individuals by meta-analytic techniques, whose methylation assessments showed overlap across 5 consecutive CpG sites (GRCh37/hg19 chr5:142,783,607-142,783,639). From this information, methylation levels at CpG site 36 displayed a significant correlation to prenatal stress (r = 0.14, 95% CI: 0.05-0.23, P = 0.002). This result supports the proposed association between a specific CpG site located at the NR3C1 promoter and prenatal stress. Several confounders, such as gender, methylation at other glucocorticoid-related genes, and adjustment for pharmacological treatments during pregnancy, should be taken into account in further studies.
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“There is now consistent evidence for a link between pregnancy stress (including perceived stress, anxiety, depression, and natural disasters) and increased DNA methylation of NR3C1 in newborns [55,56], even though the studies have been quite heterogeneous in terms of the type of exposure and tissue investigated (i.e., cord blood, peripheral blood, placenta, buccal swabs).”
From Biological Embedding of Early-Life Adversity and a Scoping Review of the Evidence for Intergenerational Epigenetic Transmission of Stress and Trauma in Humans (2023) · cites this paper as [55]
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“Notwithstanding, NR3C1 has been linked to prenatal stress [140] and is the most studied gene to date related to abuse and neglect [141].”
From Food Addiction and Psychosocial Adversity: Biological Embedding, Contextual Factors, and Public Health Implications (2020) · cites this paper as [140]
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Citations
Cites
Conducting Meta-Analyses in R with the metafor Package
Viechtbauer, W. (2010) · Journal of Statistical Software · doi:10.18637/jss.v036.i03 · Cited by 20,464
Sterne, J. A. C., Sutton, A. J., Ioannidis, J. P. A., Terrin, N., Jones, D. R., Lau, J., Carpenter, J., Rucker, G., Harbord, R. M., Schmid, C. H., et al. (2011) · BMJ · doi:10.1136/bmj.d4002 · Cited by 7,709
Epigenetic programming by maternal behavior
Weaver, I. C. G., Cervoni, N., Champagne, F. A., D'Alessio, A. C., Sharma, S., Seckl, J. R., Dymov, S., Szyf, M., & Meaney, M. J. (2004) · Nature Neuroscience · doi:10.1038/nn1276 · Cited by 6,177
The combination of estimates from different experiments
Cochran, W. G. (1954) · Biometrics · doi:10.2307/3001666 · Cited by 5,380
The Handbook of Research Synthesis and Meta-Analysis
(2019) · doi:10.7758/9781610448864 · Cited by 4,553
Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse
McGowan, P. O., Sasaki, A., D'Alessio, A. C., Dymov, S., Labonté, B., Szyf, M., Turecki, G., & Meaney, M. J. (2009) · Nature Neuroscience · doi:10.1038/nn.2270 · Cited by 3,531
The Corticosteroid Receptor Hypothesis of Depression
Holsboer, F. (2000) · Neuropsychopharmacology · doi:10.1016/s0893-133x(00)00159-7 · Cited by 2,181
Oberlander, T. F., Weinberg, J., Papsdorf, M., Grunau, R., Misri, S., & Devlin, A. M. (2008) · Epigenetics · doi:10.4161/epi.3.2.6034 · Cited by 1,432
Chronic stress, glucocorticoid receptor resistance, inflammation, and disease risk
Cohen, S., Janicki-Deverts, D., Doyle, W. J., Miller, G. E., Frank, E., Rabin, B. S., & Turner, R. B. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1118355109 · Cited by 1,419
Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?
Hanson, M. A., & Gluckman, P. D. (2014) · Physiological Reviews · doi:10.1152/physrev.00029.2013 · Cited by 1,188
Sex-Specific Programming of Offspring Emotionality after Stress Early in Pregnancy
Mueller, B. R., & Bale, T. L. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.1424-08.2008 · Cited by 988
Review: Sex and the human placenta: Mediating differential strategies of fetal growth and survival
Clifton, V. L. (2010) · Placenta · doi:10.1016/j.placenta.2009.11.010 · Cited by 868
Glucocorticoid exposure in utero: new model for adult hypertension
Benediktsson, R., Lindsay, R. S., Noble, J., Seckl, J. R., & Edwards, C. R. W. (1993) · The Lancet · doi:10.1016/0140-6736(93)90138-7 · Cited by 862
Miller, G. E., Chen, E., Fok, A. K., Walker, H., Lim, A., Nicholls, E. F., Cole, S., & Kobor, M. S. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0902971106 · Cited by 822
Prenatal exposure to the Dutch famine and disease in later life: An overview
Painter, R. C., Roseboom, T. J., & Bleker, O. P. (2005) · Reproductive Toxicology · doi:10.1016/j.reprotox.2005.04.005 · Cited by 784
Child maltreatment and the developing HPA axis
Tarullo, A. R., & Gunnar, M. R. (2006) · Hormones and Behavior · doi:10.1016/j.yhbeh.2006.06.010 · Cited by 737
Temporal dynamics and genetic control of transcription in the human prefrontal cortex
Colantuoni, C., Lipska, B. K., Ye, T., Hyde, T. M., Tao, R., Leek, J. T., Colantuoni, E. A., Elkahloun, A. G., Herman, M. M., Weinberger, D. R., et al. (2011) · Nature · doi:10.1038/nature10524 · Cited by 685
Developmental and Functional Biology of the Primate Fetal Adrenal Cortex*
Mesiano, S. A., & Jaffe, R. B. (1997) · Endocrine Reviews · doi:10.1210/edrv.18.3.0304 · Cited by 676
Glover, V. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2011.02371.x · Cited by 569
Yehuda, R., Daskalakis, N. P., Lehrner, A., Desarnaud, F., Bader, H. N., Makotkine, I., Flory, J. D., Bierer, L. M., & Meaney, M. J. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13121571 · Cited by 514
Radtke, K. M., Ruf, M., Gunter, H. M., Dohrmann, K., Schauer, M., Meyer, A., & Elbert, T. (2011) · Translational Psychiatry · doi:10.1038/tp.2011.21 · Cited by 511 · cited 1×
“The remaining 2 papers focused on the effect of maternal exposure to violence (either intimate partner violence or war-related events) during pregnancy.(32,33) As depicted in Figure 2, there is an overlap of 5 analyzed CpG sites (35 to 39) at the promoter of the exon 1F among 6 of the 7 papers meta-analyzed herein (se…”
BackgroundReynolds, R. M. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.08.012 · Cited by 497
Kundakovic, M., Gudsnuk, K., Franks, B., Madrid, J., Miller, R. L., Perera, F. P., & Champagne, F. A. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214056110 · Cited by 490
Tyrka, A. R., Price, L. H., Marsit, C., Walters, O. C., & Carpenter, L. L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030148 · Cited by 486
Prenatal exposure to maternal stress and subsequent schizophrenia
van Os, J., & Selten, J. (1998) · The British Journal of Psychiatry · doi:10.1192/bjp.172.4.324 · Cited by 481
Maternal prenatal anxiety and downregulation of placental 11β-HSD2
O’Donnell, K. J., Bugge Jensen, A., Freeman, L., Khalife, N., O’Connor, T. G., & Glover, V. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.09.014 · Cited by 449
Lopez-Duran, N. L., Kovacs, M., & George, C. J. (2009) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.03.016 · Cited by 425
Peña, C. J., Monk, C. E., & Champagne, F. A. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039791 · Cited by 377
Teh, A. L., Pan, H., Chen, L., Ong, M.-L., Dogra, S., Wong, J., MacIsaac, J. L., Mah, S. M., McEwen, L. M., Saw, S.-M., et al. (2014) · Genome Research · doi:10.1101/gr.171439.113 · Cited by 352
Palma-Gudiel, H., Córdova-Palomera, A., Leza, J. C., & Fañanás, L. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.016 · Cited by 347
Self-citationMulligan, C., D'Errico, N., Stees, J., & Hughes, D. (2012) · Epigenetics · doi:10.4161/epi.21180 · Cited by 342
Perroud, N., Rutembesa, E., Paoloni-Giacobino, A., Mutabaruka, J., Mutesa, L., Stenz, L., Malafosse, A., & Karege, F. (2014) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2013.866693 · Cited by 336
Polymorphisms of the Glucocorticoid Receptor Gene and Major Depression
van Rossum, E. F. C., Binder, E. B., Majer, M., Koper, J. W., Ising, M., Modell, S., Salyakina, D., Lamberts, S. W. J., & Holsboer, F. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.02.007 · Cited by 329
Cao-Lei, L., Massart, R., Suderman, M. J., Machnes, Z., Elgbeili, G., Laplante, D. P., Szyf, M., & King, S. (2014) · PLoS ONE · doi:10.1371/journal.pone.0107653 · Cited by 321
Conradt, E. D., Lester, B. M., Appleton, A. A., Armstrong, D. A., & Marsit, C. J. (2013) · Epigenetics · doi:10.4161/epi.26634 · Cited by 313
Maternal prenatal depressive symptoms predict infant NR3C1 1F and BDNF IV DNA methylation
Braithwaite, E., Kundakovic, M., Ramchandani, P., Murphy, S., & Champagne, F. (2015) · Epigenetics · doi:10.1080/15592294.2015.1039221 · Cited by 299
Hompes, T., Izzi, B., Gellens, E., Morreels, M., Fieuws, S., Pexsters, A., Schops, G., Dom, M., Van Bree, R., Freson, K., et al. (2013) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2013.03.009 · Cited by 262
Sex differences in prenatal epigenetic programing of stress pathways
Bale, T. L. (2011) · Stress · doi:10.3109/10253890.2011.586447 · Cited by 249
Conversion of maternal cortisol to cortisone during placental transfer to the human fetus
Murphy, B. E. P., Clark, S. J., Donald, I. R., Pinsky, M., & Vedady, D. (1974) · American Journal of Obstetrics and Gynecology · doi:10.1016/s0002-9378(16)33697-3 · Cited by 240
King, S., Dancause, K., Turcotte‐Tremblay, A., Veru, F., & Laplante, D. P. (2012) · Birth Defects Research Part C: Embryo Today: Reviews · doi:10.1002/bdrc.21026 · Cited by 232
Welberg, L., Thrivikraman, K. V., & Plotsky, P. M. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.06374 · Cited by 229
Glover, V. A. S., & Hill, J. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.02.011 · Cited by 219
Holmes, M. C., Abrahamsen, C. T., French, K. L., Paterson, J. M., Mullins, J. J., & Seckl, J. R. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.4464-05.2006 · Cited by 200
Examining the Intersection of Sex and Stress in Modelling Neuropsychiatric Disorders
Goel, N., & Bale, T. L. (2009) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2009.01843.x · Cited by 182
Non, A. L., Binder, A. M., Kubzansky, L. D., & Michels, K. B. (2014) · Epigenetics · doi:10.4161/epi.28853 · Cited by 178
Murgatroyd, C., Quinn, J. P., Sharp, H. M., Pickles, A. R., & Hill, J. (2015) · Translational Psychiatry · doi:10.1038/tp.2014.140 · Cited by 168
Miller, G. E., Murphy, M. L. M., Cashman, R., Ma, R., Ma, J., Arevalo, J. M. G., Kobor, M. S., & Cole, S. W. (2014) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2014.05.016 · Cited by 166
Maternal PTSD associates with greater glucocorticoid sensitivity in offspring of Holocaust survivors
Lehrner, A., Bierer, L. M., Passarelli, V., Pratchett, L. C., Flory, J. D., Bader, H. N., Harris, I. R., Bedi, A., Daskalakis, N. P., Makotkine, I., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.11.019 · Cited by 160
Consequences of prenatal toxin exposure for mental health in children and adolescents
Williams, J. H. G., & Ross, L. (2007) · European Child & Adolescent Psychiatry · doi:10.1007/s00787-006-0596-6 · Cited by 158
Sharp, H. M., Pickles, A. R., Meaney, M. J., Marshall, K. H., Tibu, F., & Hill, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045446 · Cited by 146
Murphy, V. E., Zakár, T., Smith, R., Giles, W. B., Gibson, P. G., & Clifton, V. L. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.4.8377 · Cited by 132
Bromer, C., Marsit, C. J., Armstrong, D. A., Padbury, J. F., & Lester, B. M. (2012) · Developmental Psychobiology · doi:10.1002/dev.21061 · Cited by 116
(2015) · Cited by 104
Stroud, L. R., Papandonatos, G. D., Rodriguez, D., McCallum, M., Salisbury, A. L., Phipps, M. G., Lester, B., Huestis, M. A., Niaura, R., Padbury, J. F., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.05.017 · Cited by 104
Current concepts in glucocorticoid resistance
Yang, N., Ray, D. W., & Matthews, L. C. (2012) · Steroids · doi:10.1016/j.steroids.2012.05.007 · Cited by 92
Nieratschker, V., Massart, R., Gilles, M., Luoni, A., Suderman, M. J., Krumm, B., Meier, S., Witt, S. H., Nöthen, M. M., Suomi, S. J., et al. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.75 · Cited by 83
Self-citationKofink, D., Boks, M. P. M., Timmers, H. T. M., & Kas, M. J. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.03.020 · Cited by 83
Naumova, O. Y., Lee, M., Rychkov, S. Y., Vlasova, N. V., & Grigorenko, E. L. (2012) · Child Development · doi:10.1111/cdev.12014 · Cited by 81
Combining adjusted and unadjusted findings in mixed research synthesis
Voils, C. I., Crandell, J., Chang, Y., Leeman, J., & Sandelowski, M. (2010) · Journal of Evaluation in Clinical Practice · doi:10.1111/j.1365-2753.2010.01444.x · Cited by 74
Examining the joint contribution of placental NR3C1 and HSD11B2 methylation for infant neurobehavior
Appleton, A. A., Lester, B. M., Armstrong, D. A., Lesseur, C., & Marsit, C. J. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.11.004 · Cited by 72
DNA methylation in neonates born to women receiving psychiatric care
Schroeder, J. W., Smith, A. K., Brennan, P. A., Conneely, K. N., Kilaru, V., Knight, B. T., Newport, D. J., Cubells, J. F., & Stowe, Z. N. (2012) · Epigenetics · doi:10.4161/epi.19551 · Cited by 71
Conradt, E. D., Fei, M., LaGasse, L. L., Tronick, E. Z., Guerin, D. J., Gorman, D., Marsit, C. J., & Lester, B. M. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00130 · Cited by 63
Delisle, H. F. (2002) · World Health Organization eBooks · Cited by 53
Natural selection In Utero : Evidence from the great East Japan earthquake
Catalano, R. A., Yorifuji, T., & Kawachi, I. (2013) · American Journal of Human Biology · doi:10.1002/ajhb.22414 · Cited by 45
Turner, J. D., Vernocchi, S., Schmitz, S., & Muller, C. P. (2014) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2014.08.010 · Cited by 40
Research works printed but not linked: 3
- Mesiano S, 1997, Endocr Rev, 18, 378
- Murphy VE, 2002, J Clin Endocrinol Metab, 87, 1660
- Van Os J, 1998, The May 1940 Invasion of The Netherlands. Br J Psychiat, 172, 324
Cited by
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Koss, K. J., & Gunnar, M. R. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12784 · Cited by 489
Garner, A., Yogman, M., COMMITTEE ON PSYCHOSOCIAL ASPECTS OF CHILD AND FAMILY HEALTH, Lavin, A., Askew, G. L., Baum, R. A., Berger-Jenkins, E., Johnson, T. J., Jutte, D., Nasir, A. A., et al. (2021) · Pediatrics · doi:10.1542/peds.2021-052582 · Cited by 392
Prenatal Stress, Glucocorticoids, and Developmental Programming of the Stress Response
McGowan, P. O., & Matthews, S. G. (2017) · Endocrinology · doi:10.1210/en.2017-00896 · Cited by 278
Buss, C., Entringer, S., Moog, N. K., Toepfer, P., Fair, D. A., Simhan, H. N., Heim, C. M., & Wadhwa, P. D. (2017) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2017.03.001 · Cited by 250
Metadata
- Authors
- Palma-Gudiel, H., Córdova-Palomera, A., Eixarch, E., Deuschle, M., & Fañanás, L.
- Affiliations
- Hospital Sant Joan de Déu Barcelona (ES)
- University of Mannheim (DE)
- Centro de Investigación Biomédica en Red de Salud Mental (ES)
- Corresponding author
- Fañanás, L
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2015-09
- Volume
- 10
- Issue
- 10
- Pages
- 893-902
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC4844196
- OpenAlex
- W1851806939
- Cited by
- 240
- References
- 65
- Citations by year
- 2026: 15 · 2025: 19 · 2024: 22 · 2023: 29 · 2022: 18 · 2021: 21 · 2020: 25 · 2019: 22 · 2018: 30 · 2017: 27 · 2016: 12
- FWCI
- 3.49
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epigenetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universitat Pompeu Fabra
- University of Reading
- Generalitat de Catalunya (2014SGR1636)
- Departament d'Innovació, Universitats i Empresa, Generalitat de Catalunya
- Ministerio de Ciencia e Innovación (PIM2010ERN-00642, SAF2008-05674-C03-01)
- Centro de Investigación Biomédica en Red de Salud Mental
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- prenatal stress, maternal psychosocial stress, glucocorticoid receptor, NR3C1, DNA methylation, promoter methylation, CpG sites, developmental programming, hypothalamic-pituitary-adrenal axis, pregnancy
- MeSH terms
- Female, Humans, Male, Pituitary-Adrenal System, Pregnancy, Prenatal Exposure Delayed Effects, Promoter Regions, Genetic, Receptors, Glucocorticoid, Stress, Psychological, CpG Islands, DNA Methylation, Epigenesis, Genetic
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