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Maternal Stress Induces Epigenetic Signatures of Psychiatric and Neurological Diseases in the Offspring
Open accessAbstract
The gestational state is a period of particular vulnerability to diseases that affect maternal and fetal health. Stress during gestation may represent a powerful influence on maternal mental health and offspring brain plasticity and development. Here we show that the fetal transcriptome, through microRNA (miRNA) regulation, responds to prenatal stress in association with epigenetic signatures of psychiatric and neurological diseases. Pregnant Long-Evans rats were assigned to stress from gestational days 12 to 18 while others served as handled controls. Gestational stress in the dam disrupted parturient maternal behaviour and was accompanied by characteristic brain miRNA profiles in the mother and her offspring, and altered transcriptomic brain profiles in the offspring. In the offspring brains, prenatal stress upregulated miR-103, which is involved in brain pathologies, and downregulated its potential gene target Ptplb. Prenatal stress downregulated miR-145, a marker of multiple sclerosis in humans. Prenatal stress also upregulated miR-323 and miR-98, which may alter inflammatory responses in the brain. Furthermore, prenatal stress upregulated miR-219, which targets the gene Dazap1. Both miR-219 and Dazap1 are putative markers of schizophrenia and bipolar affective disorder in humans. Offspring transcriptomic changes included genes related to development, axonal guidance and neuropathology. These findings indicate that prenatal stress modifies epigenetic signatures linked to disease during critical periods of fetal brain development. These observations provide a new mechanistic association between environmental and genetic risk factors in psychiatric and neurological disease.
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“An opposite effect was observed in male rats exposed to maternal gestational psychosocial stress, where there were increased levels of whole-brain miR-219 [108], which shows oligodendrocyte-enriched expression [107] and is necessary for enabling and promoting the maturation of oligodendrocyte precursor cells into myelinating oligodendrocytes [140, 141].”
From Cell-type-specific epigenetic effects of early life stress on the brain (2022) · cites this paper as [108]
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1 retracted
Owen, D., Andrews, M. H., & Matthews, S. G. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.10.004 · Cited by 211
RetractedCluster analysis and display of genome-wide expression patterns
Eisen, M. B., Spellman, P. T., Brown, P. O., & Botstein, D. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.25.14863 · Cited by 16,184
Bolstad, B. M., Irizarry, R. A., Åstrand, M., & Speed, T. P. (2003) · Bioinformatics · doi:10.1093/bioinformatics/19.2.185 · Cited by 8,328
Vyas, A., Mitra, R., Shankaranarayana Rao, B. S., & Chattarji, S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06810.2002 · Cited by 1,662
Sempere, L. F., Freemantle, S., Pitha-Rowe, I., Moss, E., Dmitrovsky, E., & Ambros, V. (2004) · Genome Biology · doi:10.1186/gb-2004-5-3-r13 · Cited by 1,578
A microRNA array reveals extensive regulation of microRNAs during brain development
KRICHEVSKY, A. M., KING, K. S., DONAHUE, C. P., KHRAPKO, K., & KOSIK, K. S. (2003) · RNA · doi:10.1261/rna.5980303 · Cited by 1,040
Meaney, M. J., Diorio, J., Francis, D., Widdowson, J., LaPlante, P., Caldji, C., Sharma, S., Seckl, J. R., & Plotsky, P. M. (2010) · Developmental Neuroscience · doi:10.1159/000111395 · Cited by 878
Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes
Huang, J., Wang, F., Argyris, E. G., Chen, K., Liang, Z., Tian, H., Huang, W., Squires, K., Verlinghieri, G., & Zhang, H. (2007) · Nature Medicine · doi:10.1038/nm1639 · Cited by 766
Epigenetics as a unifying principle in the aetiology of complex traits and diseases
Petronis, A. (2010) · Nature · doi:10.1038/nature09230 · Cited by 703
Nelson, E. E., & Panksepp, J. (1998) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(97)00052-3 · Cited by 688 · cited 1×
“If antepartum activities are somewhat predictive of postpartum maternal care [55,26,3], even a moderate behavioural change in maternal behaviour may potentially have significant consequences for offspring development.”
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Research works printed but not linked: 3
- H Schultz, 1888, Über Hefegifte (about yeast poisons), Pflugers Archive, 42, 517
- M Connolly, 2011, MiR-323, a novel microRNA in rheumatoid arthritis, promotes the activated phenotype of synovial fibroblasts, Arthritis Rheum, 63, 1672
- EC Cottrell, 2009, Prenatal stress, glucocorticoids and the programming of adult disease, Front Behav Neurosci, 3, 19, 10.3389/neuro.08.019.2009 · DOI · Paper page
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Modulation of the Hypothalamic-Pituitary-Adrenal Axis by Early Life Stress Exposure
van Bodegom, M., Homberg, J. R., & Henckens, M. J. A. G. (2017) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2017.00087 · Cited by 606
Deans, C., & Maggert, K. A. (2015) · Genetics · doi:10.1534/genetics.114.173492 · Cited by 554
Babenko, O., Kovalchuk, I., & Metz, G. A. S. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.11.013 · Cited by 513
Self-citationGlucocorticoids and fetal programming part 2: mechanisms
Moisiadis, V. G., & Matthews, S. G. (2014) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2014.74 · Cited by 448
Epigenetics across the human lifespan
Kanherkar, R. R., Bhatia-Dey, N., & Csoka, A. B. (2014) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2014.00049 · Cited by 407
Metadata
- Authors
- Zucchi, F. C. R., Yao, Y., Ward, I. D., Ilnytskyy, Y., Olson, D. M., Benzies, K., Kovalchuk, I., Kovalchuk, O., & Metz, G. A. S.
- Affiliations
- University of Lethbridge (CA)
- University of Alberta (CA)
- University of Calgary (CA)
- Corresponding author
- Metz, Gerlinde A. S.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-02-22
- Volume
- 8
- Issue
- 2
- Pages
- e56967
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3579944
- OpenAlex
- W2016612502
- Cited by
- 193
- References
- 100
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 12 · 2022: 13 · 2021: 12 · 2020: 19 · 2019: 13 · 2018: 18 · 2017: 20 · 2016: 18 · 2015: 21 · 2014: 24 · 2013: 6
- FWCI
- 23.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Alberta Innovates (200700595)
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Keywords
- prenatal stress, maternal stress, epigenetic signatures, microRNA, offspring neurodevelopment, miR-103, miR-145, miR-219, miR-98, DAZAP1, schizophrenia, bipolar disorder, multiple sclerosis, neuroinflammation, Long-Evans rats, environmental risk factors
- MeSH terms
- Animals, Base Sequence, Mental Disorders, Brain, Female, Nervous System Diseases, Pregnancy, Pregnancy Complications, Stress, Psychological, DNA Primers, Reverse Transcriptase Polymerase Chain Reaction, Rats, Long-Evans, MicroRNAs, Epigenesis, Genetic, Transcriptome, Real-Time Polymerase Chain Reaction
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