Sex-Specific Programming of Offspring Emotionality after Stress Early in Pregnancy
Open accessAbstract
Prenatal stress is associated with an increased vulnerability to neurodevelopmental disorders, including autism and schizophrenia. To determine the critical time window when fetal antecedents may induce a disease predisposition, we examined behavioral responses in offspring exposed to stress during early, mid, and late gestation. We found that male offspring exposed to stress early in gestation displayed maladaptive behavioral stress responsivity, anhedonia, and an increased sensitivity to selective serotonin reuptake inhibitor treatment. Long-term alterations in central corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR) expression, as well as increased hypothalamic–pituitary–adrenal (HPA) axis responsivity, were present in these mice and likely contributed to an elevated stress sensitivity. Changes in CRF and GR gene methylation correlated with altered gene expression, providing important evidence of epigenetic programming during early prenatal stress. In addition, we found the core mechanism underlying male vulnerability may involve sex-specific placenta responsivity, where stress early in pregnancy significantly increased expression of PPARα (peroxisome proliferator-activated receptor α), IGFBP-1 (insulin-like growth factor binding protein 1), HIF3α (hypoxia-inducible factor 3a), and GLUT4 (glucose transporter 4) in male placentas but not females. Examination of placental epigenetic machinery revealed basal sex differences, providing further evidence that sex-specific programming begins very early in pregnancy, and may contribute to the timing and vulnerability of the developing fetus to maternal perturbations. Overall, these results indicate that stress experience early in pregnancy may contribute to male neurodevelopmental disorders through impacts on placental function and fetal development.
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In animal models of prenatal stress, exposure to chronic stress in utero increased male, but not female, HPA stress reactivity.
“exposure to chronic stress in utero increased male, but not female, HPA stress reactivity (e.g., behavioral response to the tail suspension test) 159,162”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [159]
The Prenatal Stress Methods describe chronic variable stress during gestation, and the HPA Axis Stress Response Results report elevated corticosterone after restraint in males exposed to stress early in gestation. The Discussion reports altered tail-suspension behavior in males but not females; however, HPA-axis reactivity was measured only in males, so the source does not establish that female HPA reactivity was unchanged. (LLM, conf=0.87)
Experimental — accuracy not yet measuredEarly gestational stress exposure led to sex differences in expression and methylation of genes in the placenta associated with growth and nutrient transport.
“early gestational stress exposure led to sex differences in expression and methylation of genes in the placenta associated with growth and nutrient transport 159”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [159]
The Results section reports sex-specific changes in placental expression of genes associated with growth and nutrient transport after early prenatal stress. It also reports changes in expression of the methylation-maintenance enzyme DNMT1, but does not report methylation changes in those placental genes themselves (page numbers unavailable in our copy). (LLM, conf=0.90)
Experimental — accuracy not yet measuredPrenatal stress has different effects in male vs. female offspring.
“prenatal stress has different effects in male vs. female offspring 143,159-161”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [159]
Among mice exposed to stress during early, mid and late gestation, male F1 with early gestation prenatal stress exposure demonstrated behavioral indicators of stress responsivity and anhedonia, as well as alterations in GR and CRF expression and increased HPA axis responsivity, with corresponding alteration in CRF and nr3c1 gene methylation.
“Among mice exposed to stress during early, mid and late gestation, male F1 with early gestation prenatal stress exposure demonstrated behavioral indicators of stress responsivity and anhedonia, as well as alterations in GR and corticotrophin-releasing factor (CRF) expression and increased HPA axis responsivity, with corresponding alteration in CRF and nr3c1 gene methylation 159”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [159]
These behaviors were transmitted to the next generation through the male germ line.
“These behaviors were transmitted to the next generation through the male germ line.”
From Intergenerational transmission of trauma effects: putative role of epigenetic mechanisms (2018) · cites this paper as [159]
The Materials and Methods section reports depressive-like behaviors in male offspring exposed to stress during gestation. Neither that section nor the Results and Discussion passages establish transmission to another generation through the male germ line; searches for germline, sperm, paternal inheritance, and F2 offspring found no such evidence. Page numbers were not available in our copy. (LLM, conf=0.76)
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Cites
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859 · see citing works
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395 · see citing works
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 · see citing works
The tail suspension test: A new method for screening antidepressants in mice
Steru, L., Chermat, R., Thierry, B., & Simon, P. (1985) · Psychopharmacology · doi:10.1007/bf00428203 · Cited by 3,534 · see citing works
Nestler, E. J., Barrot, M., DiLeone, R. J., Eisch, A. J., Gold, S. J., & Monteggia, L. M. (2002) · Neuron · doi:10.1016/s0896-6273(02)00653-0 · Cited by 3,217 · see citing works
Epigenetic regulation in psychiatric disorders
Tsankova, N., Renthal, W., Kumar, A., & Nestler, E. J. (2007) · Nature reviews. Neuroscience · doi:10.1038/nrn2132 · Cited by 1,400 · see citing works
CRF and CRF receptors: role in stress responsivity and other behaviors
Bale, T. L., & Vale, W. W. (2004) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.44.101802.121410 · Cited by 1,270 · see citing works
Self-citationA targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei
Leonhardt, H., Page, A. W., Weier, H.-U., & Bestor, T. H. (1992) · Cell · doi:10.1016/0092-8674(92)90561-p · Cited by 1,050 · see citing works
Bale, T. L., Contarino, A., Smith, G. W., Chan, R. K. W., Gold, L. H., Sawchenko, P. E., Koob, G. F., Vale, W. W., & Lee, K. (2000) · Nature Genetics · doi:10.1038/74263 · Cited by 850 · see citing works
Self-citationLucki, I. (1997) · Behavioural Pharmacology · doi:10.1097/00008877-199711000-00010 · Cited by 803 · see citing works
Epigenetic mechanisms of perinatal programming of hypothalamic-pituitary-adrenal function and health
Meaney, M. J., Moshe Szyf, A., & Seckl, J. R. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.05.003 · Cited by 660 · see citing works
Stress and the hypothalamic pituitary adrenal axis in the developmental course of schizophrenia
Walker, E., Mittal, V., & Tessner, K. (2008) · Annual Review of Clinical Psychology · doi:10.1146/annurev.clinpsy.4.022007.141248 · Cited by 615 · see citing works
Khashan, A. S., Abel, K. M., McNamee, R., Pedersen, M. G., Webb, R. T., Baker, P. N., Kenny, L. C., & Mortensen, P. B. (2008) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2007.20 · Cited by 576 · see citing works
SECKL, J. R., & MEANEY, M. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1314.006 · Cited by 556 · see citing works
Pardo, C. A., & Eberhart, C. G. (2007) · Brain Pathology · doi:10.1111/j.1750-3639.2007.00102.x · Cited by 514 · see citing works
Epigenetic programming of the stress response in male and female rats by prenatal restraint stress
Darnaudéry, M., & Maccari, S. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.11.004 · Cited by 412 · see citing works
Levels of anxiety and sources of stress in adults with autism
Gillott, A., & Standen, P. J. (2007) · Journal of Intellectual Disabilities · doi:10.1177/1744629507083585 · Cited by 359 · see citing works
Weaver, I. C. G., Diorio, J. C., Seckl, J. R., Moshe Szyf, A., & Meaney, M. J. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1321.099 · Cited by 330 · see citing works
Rivera, R. M., Stein, P., Weaver, J. R., Mager, J., Schultz, R. M., & Bartolomei, M. S. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm280 · Cited by 324 · see citing works
Cryan, J. F., Page, M. E., & Lucki, I. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0093-5 · Cited by 321 · see citing works
Cure therapeutics and strategic prevention: raising the bar for mental health research
Insel, T. R., & Scolnick, E. M. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001777 · Cited by 313 · see citing works
Valentino, R. J., Page, M. E., & Curtis, A. L. (1991) · Brain Research · doi:10.1016/0006-8993(91)90855-p · Cited by 246 · see citing works
Regulation of the peroxisome proliferator-activated receptor alpha gene by glucocorticoids.
Lemberger, T., Staels, B., Saladin, R., Desvergne, B., Auwerx, J. H., & Wahli, W. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31420-5 · Cited by 233 · see citing works
McGill, B. E., Bundle, S. F., Yaylaoglu, M., Carson, J. P., Christina Thaller, B., & Zoghbi, H. Y. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0608702103 · Cited by 229 · see citing works
Prenatal teratogens and the development of adult mental illness
WATSON, J. B., MEDNICK, S. A., HUTTUNEN, M., & WANG, X. (1999) · Development and Psychopathology · doi:10.1017/s0954579499002151 · Cited by 224 · see citing works
Early prenatal stress impact on coping strategies and learning performance is sex dependent
Mueller, B. R., & Bale, T. L. (2007) · Physiology & Behavior · doi:10.1016/j.physbeh.2007.01.017 · Cited by 216 · see citing works
Self-citationHagan, M. M., Chandler-Laney, P. C., Wauford, P. K., Rybak, R. J., & Oswald, K. D. (2003) · International Journal of Eating Disorders · doi:10.1002/eat.10168 · Cited by 202 · see citing works
Cratty, M. S., Ward, H. E., Johnson, E. A., Azzaro, A. J., & Birkle, D. L. (1995) · Brain Research · doi:10.1016/0006-8993(95)00087-7 · Cited by 201 · see citing works
Glucocorticoid hormones and early brain development in schizophrenia
Ph.D., J. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00396-7 · Cited by 199 · see citing works
Avena, N. M., Rada, P. V., Moise, N., & Hoebel, B. G. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.12.037 · Cited by 195 · see citing works
Decreases in Dietary Preference Produce Increased Emotionality and Risk for Dietary Relapse
Teegarden, S. L., & Bale, T. L. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.032 · Cited by 188 · see citing works
Self-citationImpact of prenatal stress on long term body weight is dependent on timing and maternal sensitivity
MUELLER, B., & Bale, T. L. (2006) · Physiology & Behavior · doi:10.1016/j.physbeh.2006.05.019 · Cited by 162 · see citing works
Self-citationStrain-dependent antidepressant-like effects of citalopram in the mouse tail suspension test
Crowley, J. J., Blendy, J. A., & Lucki, I. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0166-5 · Cited by 158 · see citing works
Liu, T., Zhang, X., So, C., Wang, S., Wang, P., Yan, L., Myers, R., Chen, Z., Patterson, A. P., Yang, C. S., et al. (2006) · Carcinogenesis · doi:10.1093/carcin/bgl176 · Cited by 155 · see citing works
Weaver, I. C. G., Plante, P. L., Weaver, S., Parent, A., Sharma, S., Diorio, J. C., Chapman, K. E., Seckl, J. R., Moshe Szyf, A., & Meaney, M. J. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00635-9 · Cited by 154 · see citing works
Transcription of the sex-determining region genes Sry and Zfy in the mouse preimplantation embryo.
Zwingman, T. A., Erickson, R. P., Boyer, T., & Ao, A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.3.814 · Cited by 133 · see citing works
Tan, H., Zhong, P., & Yan, Z. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0143-04.2004 · Cited by 112 · see citing works
Epigenetic landscape required for placental development
Hemberger, M. (2007) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-007-7113-z · Cited by 107 · see citing works
Malberg, J. E., Platt, B., Rizzo, S. J. S., Ring, R. H., Lucki, I., Schechter, L. E., & Rosenzweig-Lipson, S. (2007) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301358 · Cited by 101 · see citing works
Bale, T. L., Anderson, K. R., Roberts, A. J., et al. (2003) · Endocrinology · doi:10.1210/en.2002-0091 · Cited by 83 · see citing works
Self-citationPrenatal stress and childhood psychopathology
Ward, A. J. (1991) · Child Psychiatry & Human Development · doi:10.1007/bf00707788 · Cited by 82 · see citing works
Wang, H., Ogawa, M., Wood, J. R., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddm381 · Cited by 76 · see citing works
Lynch, W. J., & Taylor, J. R. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300656 · Cited by 69 · see citing works
[Validation of an animal model of anhedonia, a major symptom of depression].
Moreau, J. (1997) · PubMed · Cited by 67 · see citing works
Down-Regulation of IL-7Rα Expression in Human T Cells via DNA Methylation
Kim, H., Hwang, K., Kim, K.-C., & Kang, I. (2007) · The Journal of Immunology · doi:10.4049/jimmunol.178.9.5473 · Cited by 64 · see citing works
Degenhardt, T., Heinäniemi, M., Herzig, K., Dunlop, T. W., & Carlberg, C. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m605623200 · Cited by 62 · see citing works
Neuronal cytoskeletal alterations in an experimental model of depression
Reinés, A. G., Cereseto, M., Ferrero, A., Bonavita, C. D., & Wikinski, S. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.08.026 · Cited by 53 · see citing works
Cryan, J. F., & Lucki, I. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00858-x · Cited by 43 · see citing works
Valentino, R. J., & Curtis, A. L. (1991) · PubMed · Cited by 38 · see citing works
Altay, T., Gonzales, E. R., Park, T. S., & Gidday, J. M. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00798.2003 · Cited by 29 · see citing works
Miguel-Hidalgo, J. J., Dubey, P., Shao, Q., Stockmeier, C. A., & Rajkowska, G. (2005) · Schizophrenia Research · doi:10.1016/j.schres.2005.02.015 · Cited by 23 · see citing works
Weatherly, J. N., & Arthur, E. I. L. (2006) · The Journal of General Psychology · doi:10.3200/genp.133.1.81-95 · Cited by 2 · see citing works
Flagged first, then by citations
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- Mueller BR Bale TL Early prenatal stress impact on coping strategies and learning performance is sex dependent Physiol Behav 2007b 91 55 65 17367828
Cited by
Sorted by citations
Sex differences in anxiety and depression clinical perspectives
Altemus, M., Sarvaiya, N., & Neill Epperson, C. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.05.004 · Cited by 1,413 · see citing works
Lasting epigenetic influence of early-life adversity on the BDNF gene
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.11.028 · Cited by 1,273 · see citing works
Early Life Programming and Neurodevelopmental Disorders
Bale, T. L., Baram, T. Z., Brown, A. S., Goldstein, J. M., Insel, T. R., McCarthy, M. M., Nemeroff, C. B., Reyes, T. M., Simerly, R. B., Susser, E. S., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.05.028 · Cited by 961 · see citing works
Self-citation11β-hydroxysteroid dehydrogenases: Intracellular gate-keepers of tissue glucocorticoid action
Chapman, K., Holmes, M., & Seckl, J. (2013) · Physiological Reviews · doi:10.1152/physrev.00020.2012 · Cited by 887 · see citing works
Glucocorticoids, prenatal stress and the programming of disease
Harris, A., & Seckl, J. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.06.007 · Cited by 871 · see citing works
Maternal depression, anxiety and stress during pregnancy and child outcome; what needs to be done
Glover, V. (2014) · Best Practice & Research Clinical Obstetrics & Gynaecology · doi:10.1016/j.bpobgyn.2013.08.017 · Cited by 818 · see citing works
Rodgers, A. B., Morgan, C. P., Bronson, S. L., Revello, S., & Bale, T. L. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.0914-13.2013 · Cited by 814 · see citing works
Self-citationTurecki, G., & Meaney, M. J. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2014.11.022 · Cited by 796 · see citing works
Sex differences and stress across the lifespan
Bale, T. L., & Epperson, C. N. (2015) · Nature Neuroscience · doi:10.1038/nn.4112 · Cited by 751 · see citing works
Self-citationIntergenerational transmission of trauma effects: putative role of epigenetic mechanisms
Yehuda, R., & Lehrner, A. (2018) · World Psychiatry · doi:10.1002/wps.20568 · Cited by 730 · see citing works
Pathogenesis of depression: Insights from human and rodent studies
Ménard, C., Hodes, G. E., & Russo, S. J. (2016) · Neuroscience · doi:10.1016/j.neuroscience.2015.05.053 · Cited by 593 · see citing works
Boys live dangerously in the womb
Eriksson, J. G., Kajantie, E., Osmond, C., Thornburg, K., & Barker, D. J. P. (2010) · American Journal of Human Biology · doi:10.1002/ajhb.20995 · Cited by 590 · see citing works
Glover, V. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2011.02371.x · Cited by 569 · see citing works
Babenko, O., Kovalchuk, I., & Metz, G. A. S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.013 · Cited by 513 · see citing works
Critical period regulation across multiple timescales
Reh, R. K., Dias, B. G., Nelson, C. A., Kaufer, D., Werker, J. F., Kolb, B., Levine, J. D., & Hensch, T. K. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1820836117 · Cited by 492 · see citing works
Epigenetic and transgenerational reprogramming of brain development
Bale, T. L. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn3818 · Cited by 505 · see citing works
Self-citationKundakovic, 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 · see citing works
Resilience to social stress coincides with functional DNA methylation of the Crf gene in adult mice
Elliott, E., Ezra-Nevo, G., Regev, L., Neufeld-Cohen, A., & Chen, A. (2010) · Nature Neuroscience · doi:10.1038/nn.2642 · Cited by 436 · see citing works
DNA methylation of BDNF as a biomarker of early-life adversity
Kundakovic, M., Gudsnuk, K., Herbstman, J. B., Tang, D., Perera, F. P., & Champagne, F. A. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1408355111 · Cited by 426 · see citing works
Sex Differences in Vulnerability and Resilience to Stress Across the Life Span
Hodes, G. E., & Epperson, C. N. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.04.028 · Cited by 417 · see citing works
Activation of the maternal immune system induces endocrine changes in the placenta via IL-6
Hsiao, E. Y., & Patterson, P. H. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.12.017 · Cited by 402 · see citing works
Prenatal developmental origins of future psychopathology: mechanisms and pathways
Monk, C., Lugo-Candelas, C., & Trumpff, C. (2019) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-050718-095539 · Cited by 388 · see citing works
Immune and neuroendocrine mechanisms of stress vulnerability and resilience
Ménard, C., Pfau, M. L., Hodes, G. E., & Russo, S. J. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2016.90 · Cited by 374 · see citing works
Epigenetic regulation of gene expression in physiological and pathological brain processes
Gräff, J., Kim, D., Dobbin, M. M., & Tsai, L.-H. (2011) · Physiological Reviews · doi:10.1152/physrev.00012.2010 · Cited by 373 · see citing works
Epigenetic influences on brain development and plasticity
Fagiolini, M., Jensen, C. L., & Champagne, F. A. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.009 · Cited by 362 · see citing works
Morgan, C. P., & Bale, T. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.1887-11.2011 · Cited by 346 · see citing works
Self-citationEpigenetic basis of mental illness
Nestler, E. J., Peña, C. J., Kundakovic, M., Mitchell, A., & Akbarian, S. (2016) · The Neuroscientist · doi:10.1177/1073858415608147 · Cited by 342 · see citing works
Gabory, A., Roseboom, T. J., Moore, T., Moore, L. G., & Junien, C. (2013) · Biology of Sex Differences · doi:10.1186/2042-6410-4-5 · Cited by 344 · see citing works
Is there a viability–vulnerability tradeoff? Sex differences in fetal programming
Sandman, C. A., Glynn, L. M., & Davis, E. P. (2013) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2013.07.009 · Cited by 343 · see citing works
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 · see citing works
Jašarević, E., Howerton, C. L., Howard, C. D., & Bale, T. L. (2015) · Endocrinology · doi:10.1210/en.2015-1177 · Cited by 329 · see citing works
Self-citationGenetics of Human Social Behavior
Ebstein, R. P., Israel, S., Chew, S. H., Zhong, S., & Knafo, A. (2010) · Neuron · doi:10.1016/j.neuron.2010.02.020 · Cited by 323 · see citing works
The neuroendocrinology of the microbiota-gut-brain axis: a behavioural perspective
Cussotto, S., Sandhu, K. V., Dinan, T. G., & Cryan, J. F. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.04.002 · Cited by 326 · see citing works
Bronson, S. L., & Bale, T. L. (2014) · Endocrinology · doi:10.1210/en.2014-1040 · Cited by 299 · see citing works
Self-citationThe neurodevelopmental origins of suicidal behavior
Turecki, G., Ernst, C., Jollant, F., Labonté, B., & Mechawar, N. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2011.11.008 · Cited by 299 · see citing works
Maternal prenatal depressive symptoms predict infant<i>NR3C1</i>1F and<i>BDNF</i>IV DNA methylation
Braithwaite, E., Kundakovic, M., Ramchandani, P., Murphy, S., & Champagne, F. (2015) · Epigenetics · doi:10.1080/15592294.2015.1039221 · Cited by 299 · see citing works
Epigenetic Mechanisms of Depression and Antidepressant Action
Vialou, V., Feng, J., Robison, A. J., & Nestler, E. J. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010611-134540 · Cited by 277 · see citing works
Epigenetic influence of social experiences across the lifespan
Champagne, F. A. (2010) · Developmental Psychobiology · doi:10.1002/dev.20436 · Cited by 273 · see citing works
Inflammation: A Proposed Intermediary Between Maternal Stress and Offspring Neuropsychiatric Risk
Hantsoo, L., Kornfield, S., Anguera, M. C., & Epperson, C. N. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.08.018 · Cited by 269 · see citing works
Mao, J., Zhang, X., Sieli, P. T., Falduto, M. T., Torres, K. E., & Rosenfeld, C. S. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1000440107 · Cited by 261 · see citing works
Rosenfeld, C. S. (2021) · Journal of Neuroscience Research · doi:10.1002/jnr.24603 · Cited by 280 · see citing works
The effects of early life stress on the epigenome: From the womb to adulthood and even before
Provençal, N., & Binder, E. B. (2015) · Experimental Neurology · doi:10.1016/j.expneurol.2014.09.001 · Cited by 255 · see citing works
Unternaehrer, E., Luers, P., Mill, J., Dempster, E., Meyer, A. H., Staehli, S., Lieb, R., Hellhammer, D. H., & Meinlschmidt, G. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.77 · Cited by 250 · see citing works
Glucocorticoids, developmental ‘programming’ and the risk of affective dysfunction
Seckl, J. R. (2007) · Progress in Brain Research · doi:10.1016/s0079-6123(07)67002-2 · Cited by 245 · see citing works
Parental Advisory: Maternal and Paternal Stress Can Impact Offspring Neurodevelopment
Chan, J. C., Nugent, B. M., & Bale, T. L. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.10.005 · Cited by 241 · see citing works
Self-citationHeim, C. (2009) · Frontiers in Behavioral Neuroscience · doi:10.3389/neuro.08.041.2009 · Cited by 245 · see citing works
Roth, T. L., & David Sweatt, J. (2011) · Journal of Child Psychology and Psychiatry · doi:10.1111/j.1469-7610.2010.02282.x · Cited by 246 · see citing works
The omniscient placenta: Metabolic and epigenetic regulation of fetal programming
Nugent, B. M., & Bale, T. L. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.09.001 · Cited by 222 · see citing works
Self-citationPalma-Gudiel, H., Córdova-Palomera, A., Eixarch, E., Deuschle, M., & Fañanás, L. (2015) · Epigenetics · doi:10.1080/15592294.2015.1088630 · Cited by 240 · see citing works
The placenta and neurodevelopment: sex differences in prenatal vulnerability
Bale, T. L. (2016) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2016.18.4/tbale · Cited by 236 · see citing works
Self-citationPrenatal programming of postnatal plasticity?
Pluess, M., & Belsky, J. (2011) · Development and Psychopathology · doi:10.1017/s0954579410000623 · Cited by 235 · see citing works
Microbiome disturbances and autism spectrum disorders
Rosenfeld, C. S. (2015) · Drug Metabolism and Disposition · doi:10.1124/dmd.115.063826 · Cited by 229 · see citing works
Gallou-Kabani, C., Gabory, A., Tost, J., Karimi, M., Mayeur, S., Lesage, J., Boudadi, E., Gross, M.-S., Taurelle, J., Vigé, A., et al. (2010) · PLoS ONE · doi:10.1371/journal.pone.0014398 · Cited by 229 · see citing works
Kertes, D. A., Kamin, H. S., Hughes, D. A., Rodney, N. C., Bhatt, S., & Mulligan, C. J. (2016) · Child Development · doi:10.1111/cdev.12487 · Cited by 219 · see citing works
Epigenetics of stress adaptations in the brain
Stankiewicz, A. M., Swiergiel, A. H., & Lisowski, P. (2013) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2013.07.003 · Cited by 220 · see citing works
Epigenetics and the regulation of stress vulnerability and resilience
Zannas, A. S., & West, A. E. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2013.12.003 · Cited by 211 · see citing works
Prenatal Programming of Mental Illness: Current Understanding of Relationship and Mechanisms
Kim, D. R., Bale, T. L., & Epperson, C. N. (2015) · Current Psychiatry Reports · doi:10.1007/s11920-014-0546-9 · Cited by 203 · see citing works
Self-citationEarly-life adversity and brain development: Is the microbiome a missing piece of the puzzle?
O’Mahony, S. M., Clarke, G., Dinan, T. G., & Cryan, J. F. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2015.09.068 · Cited by 203 · see citing works
Epigenetic marking of the BDNF gene by early-life adverse experiences
Roth, T. L., & Sweatt, J. D. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.05.005 · Cited by 196 · see citing works
The molecular physiology of CRH neurons
Aguilera, G., & Liu, Y. (2012) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2011.08.002 · Cited by 198 · see citing works
Sex-specificity in transgenerational epigenetic programming
Dunn, G. A., Morgan, C. P., & Bale, T. L. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2010.05.004 · Cited by 198 · see citing works
Self-citationBraun, T., Challis, J. R., Newnham, J. P., & Sloboda, D. M. (2013) · Endocrine Reviews · doi:10.1210/er.2013-1012 · Cited by 196 · see citing works
Early-life stress mediated modulation of adult neurogenesis and behavior
Korosi, A., Naninck, E. F. G., Oomen, C. A., Schouten, M., Krugers, H., Fitzsimons, C., & Lucassen, P. J. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.07.037 · Cited by 194 · see citing works
Jašarević, E., Howard, C. D., Morrison, K., Misic, A., Weinkopff, T., Scott, P., Hunter, C., Beiting, D., & Bale, T. L. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0182-5 · Cited by 189 · see citing works
Epigenetic mechanisms mediating vulnerability and resilience to psychiatric disorders
Dudley, K. J., Li, X., Kobor, M. S., Kippin, T. E., & Bredy, T. W. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2010.12.016 · Cited by 180 · see citing works
Etiologies underlying sex differences in autism spectrum disorders
Schaafsma, S. M., & Pfaff, D. W. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.03.006 · Cited by 178 · see citing works
Peripheral and central mechanisms of stress resilience
Pfau, M. L., & Russo, S. J. (2015) · Neurobiology of Stress · doi:10.1016/j.ynstr.2014.09.004 · Cited by 170 · see citing works
Parent, A.-S., Franssen, D., Fudvoye, J., Gérard, A., & Bourguignon, J.-P. (2015) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.12.004 · Cited by 175 · see citing works
Vukojevic, V., Kolassa, I.-T., Fastenrath, M., Gschwind, L., Spalek, K., Milnik, A., Heck, A., Vogler, C., Wilker, S., Demougin, P., et al. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1526-14.2014 · Cited by 168 · see citing works
Epigenetic signaling in psychiatric disorders: stress and depression
Bagot, R. C., Labonté, B., Peña, C. J., & Nestler, E. J. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/rbagot · Cited by 171 · see citing works
Potential of Environmental Enrichment to Prevent Transgenerational Effects of Paternal Trauma
Gapp, K., Bohacek, J., Grossmann, J., Brunner, A. M., Manuella, F., Nanni, P., & Mansuy, I. M. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.87 · Cited by 172 · see citing works
Epigenetic Signaling in Psychiatric Disorders
Peña, C. J., Bagot, R. C., Labonté, B., & Nestler, E. J. (2014) · Journal of Molecular Biology · doi:10.1016/j.jmb.2014.03.016 · Cited by 163 · see citing works
Davis, E. P., & Pfaff, D. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.06.014 · Cited by 159 · see citing works
Stanford, K. I., Lee, M.-Y., Getchell, K. M., So, K., Hirshman, M. F., & Goodyear, L. J. (2015) · Diabetes · doi:10.2337/db13-1848 · Cited by 151 · see citing works
Pesonen, A.-K., Räikkönen, K., Feldt, K., Heinonen, K., Osmond, C., Phillips, D. I. W., Barker, D. J. P., Eriksson, J. G., & Kajantie, E. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.10.017 · Cited by 147 · see citing works
Prenatal antecedents of newborn neurological maturation
DiPietro, J. A., Kivlighan, K. T., Costigan, K. A., Rubin, S. E., Shiffler, D. E., Henderson, J. L., & Pillion, J. P. (2010) · Child Development · doi:10.1111/j.1467-8624.2009.01384.x · Cited by 143 · see citing works
Metabolic diseases and associated complications: sex and gender matter
Kautzky‐Willer, A., & Handisurya, A. (2009) · European Journal of Clinical Investigation · doi:10.1111/j.1365-2362.2009.02161.x · Cited by 138 · see citing works
Regulation of chromatin structure in memory formation
Roth, T. L., & Sweatt, J. D. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.05.011 · Cited by 138 · see citing works
Gapp, K., von Ziegler, L., Tweedie‐Cullen, R. Y., & Mansuy, I. M. (2014) · BioEssays · doi:10.1002/bies.201300116 · Cited by 136 · see citing works
Lifetime stress experience: Transgenerational epigenetics and germ cell programming
Bale, T. L. (2014) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2014.16.3/tbale · Cited by 129 · see citing works
Self-citationMilligan Armstrong, A., Porter, T., Quek, H., White, A., Haynes, J., Jackaman, C., Villemagne, V., Munyard, K., Laws, S. M., Verdile, G., et al. (2021) · Biological Reviews · doi:10.1111/brv.12750 · Cited by 116 · see citing works
Prata, J., Santos, S. G., Almeida, M. I., Coelho, R., & Barbosa, M. A. (2017) · Journal of Neuroinflammation · doi:10.1186/s12974-017-0938-y · Cited by 115 · see citing works
Abbott, P. W., Gumusoglu, S. B., Bittle, J., Beversdorf, D. Q., & Stevens, H. E. (2018) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2018.01.019 · Cited by 109 · see citing works
Champagne, F. A. (2010) · Perspectives on Psychological Science · doi:10.1177/1745691610383494 · Cited by 110 · see citing works
Effects of early-life stress on cognitive function and hippocampal structure in female rodents.
Loi, M., Mossink, J. C. L., Meerhoff, G. F., Den Blaauwen, J. L., Lucassen, P. J., & Joëls, M. (2017) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.024 · Cited by 109 · see citing works
St-Cyr, S., & McGowan, P. O. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00145 · Cited by 102 · see citing works
Rodgers, A. B., & Bale, T. L. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.03.018 · Cited by 91 · see citing works
Self-citationBartlett, A. A., Singh, R., & Hunter, R. G. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-53889-1_8 · Cited by 91 · see citing works
Cuffe, J. S. M., Dickinson, H., Simmons, D. G., & Moritz, K. M. (2011) · Placenta · doi:10.1016/j.placenta.2011.09.009 · Cited by 86 · see citing works
Taylor, P. V., Veenema, A. H., Paul, M. J., Bredewold, R., Isaacs, S., & de Vries, G. J. (2012) · Biology of Sex Differences · doi:10.1186/2042-6410-3-15 · Cited by 86 · see citing works
Gestational Factors throughout Fetal Neurodevelopment: The Serotonin Link
Hanswijk, S. I., Spoelder, M., Shan, L., Verheij, M. M. M., Muilwijk, O. G., Li, W., Liu, C., Kolk, S. M., & Homberg, J. R. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165850 · Cited by 86 · see citing works
Sze, Y., & Brunton, P. J. (2020) · European Journal of Neuroscience · doi:10.1111/ejn.14615 · Cited by 85 · see citing works
Kofink, 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 · see citing works
A meta-analysis of the association between birth weight and attention deficit hyperactivity disorder
Momany, A. M., Kamradt, J. M., & Nikolas, M. A. (2018) · Journal of Abnormal Child Psychology · doi:10.1007/s10802-017-0371-9 · Cited by 82 · see citing works
Sex differences in DNA methylation of the cord blood are related to sex-bias psychiatric diseases
Maschietto, M., Bastos, L. C., Tahira, A. C., Bastos, E. P., Euclydes, V. L. V., Brentani, A., Fink, G., de Baumont, A., Felipe-Silva, A., Francisco, R. P. V., et al. (2017) · Scientific Reports · doi:10.1038/srep44547 · Cited by 78 · see citing works
Epigenetic Alterations and Prenatal Maternal Depression
Nemoda, Z., & Szyf, M. (2017) · Birth Defects Research · doi:10.1002/bdr2.1081 · Cited by 75 · see citing works
Maternal imprints and the origins of variation
Champagne, F. A. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.02.016 · Cited by 74 · see citing works
Goldstein, J. M., Cohen, J. E., Mareckova, K., Holsen, L., Whitfield-Gabrieli, S., Gilman, S. E., Buka, S. L., & Hornig, M. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2014464118 · Cited by 70 · see citing works
Park, H. J., Kim, S. A., Kang, W. S., & Kim, J. W. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041899 · Cited by 59 · see citing works
Mechanisms of brain glucocorticoid resistance in stress-induced psychopathologies
Merkulov, V. M., Merkulova, T. I., & Bondar, N. P. (2017) · Biochemistry (Moscow) · doi:10.1134/s0006297917030142 · Cited by 65 · see citing works
- Authors
- Mueller, B. R., & Bale, T. L.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Bale, Tracy L.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2008-09-03
- Volume
- 28
- Issue
- 36
- Pages
- 9055-9065
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC2731562
- OpenAlex
- W1994740828
- Cited by
- 988
- References
- 52
- Citations by year
- 2026: 18 · 2025: 26 · 2024: 30 · 2023: 36 · 2022: 42 · 2021: 53 · 2020: 63 · 2019: 60 · 2018: 72 · 2017: 73 · 2016: 70 · 2015: 89 · 2014: 85 · 2013: 56 · 2012: 70
- FWCI
- 21.45
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- March of Dimes Foundation
- University of Pennsylvania
- National Institutes of Health (5t32mh017168-34)
- National Institute of Mental Health (T32 MH-017168)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- prenatal stress, sex differences, anhedonia, corticotropin-releasing factor, glucocorticoid receptor, hypothalamic-pituitary-adrenal axis, DNA methylation, epigenetic programming, placenta, PPARα, IGFBP-1, GLUT4, neurodevelopmental disorders, autism spectrum disorder, schizophrenia, pregnancy timing
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Corticotropin-Releasing Hormone, Emotions, Exploratory Behavior, Female, Food Preferences, Hypothalamo-Hypophyseal System, Male, Mice, Inbred C57BL, Pituitary-Adrenal System, Placenta, Pregnancy, Prenatal Exposure Delayed Effects, Raphe Nuclei, Receptors, Glucocorticoid, Sex Characteristics, Stress, Physiological, Sucrose, Swimming, Tryptophan Hydroxylase, Hindlimb Suspension, Receptor, Serotonin, 5-HT1A, Serotonin Plasma Membrane Transport Proteins, Mice
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