Cited by 193Maternal Mental Health During Pregnancy and PostpartumBirth, Development, and HealthMicroRNA in disease regulation

Maternal Stress Induces Epigenetic Signatures of Psychiatric and Neurological Diseases in the Offspring

Open access
Zucchi, Fabiola C. R., Yao, Youli, Ward, Isaac D., Ilnytskyy, Yaroslav, Olson, David M., Benzies, Karen, Kovalchuk, Igor, Kovalchuk, Olga +1 more·2013·PLoS ONE

Abstract

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.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1371/journal.pone.0056967

Cites

100 of 100 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Maternal gestational psychosocial stress increases whole-brain miR-219 in male rats.

    “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].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. [99]Cottrell EC, Seckl JR (2009) Prenatal stress, glucocorticoids and the programming of adult disease. Front Behav Neurosci 3: 19. 19826624 PMC2759372

Cited by

Sorted by citations

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
Published
2013-02-22
Volume
8
Issue
2
Pages
e56967
ISSN
1932-6203 (ISSN-L)
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
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review