Maternal stress induces eipgenetic signatures of psychiatric and neurological diseases in the offspring
Date
2013
Authors
Zucchi, Fabiola C. R.
Yao, Youli
Ward, Isaac D.
Ilnytskyy, Yaroslav
Olson, David M.
Benzies, Karen
Kovalchuk, Igor
Kovalchuk, Olga
Metz, Gerlinde A. S.
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
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.
Description
Sherpa Romeo green journal: open access
Keywords
Gestational stress , Prenatal stress , Epigenetic signatures , Offspring , Psychiatric disease , Neurological disease , Fetal brain development
Citation
Zucchi, F.C. R., Yao, Y., Ward, I. D., Ilnytskyy, Y., Olson, D. M., Benzies, K., ... Metz, G. A. S. (2013). Maternal stress induces epigenetic signatures of psychiatric and neurological diseases of the offspring. PLoS ONE 8(2), e56967. doi:10.1371.journal.pone.0056967