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PMID: 19015723 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Transgenerational epigenetic programming of the brain transcriptome and anxiety behavior.

PloS one ·Vol. 3 ·No. 11 ·2008-00-00 ·Pages e3745

Skinner MK, Anway MD, Savenkova MI, Gore AC, Crews D

Abstract

Embryonic exposure to the endocrine disruptor vinclozolin during gonadal sex determination promotes an epigenetic reprogramming of the male germ-line that is associated with transgenerational adult onset disease states. Further analysis of this transgenerational phenotype on the brain demonstrated reproducible changes in the brain transcriptome three generations (F3) removed from the exposure. The transgenerational alterations in the male and female brain transcriptomes were distinct. In the males, the expression of 92 genes in the hippocampus and 276 genes in the amygdala were transgenerationally altered. In the females, the expression of 1,301 genes in the hippocampus and 172 genes in the amygdala were transgenerationally altered. Analysis of specific gene sets demonstrated that several brain signaling pathways were influenced including those involved in axon guidance and long-term potentiation. An investigation of behavior demonstrated that the vinclozolin F3 generation males had a decrease in anxiety-like behavior, while the females had an increase in anxiety-like behavior. These observations demonstrate that an embryonic exposure to an environmental compound appears to promote a reprogramming of brain development that correlates with transgenerational sex-specific alterations in the brain transcriptomes and behavior. Observations are discussed in regards to environmental and transgenerational influences on the etiology of brain disease.

MeSH Terms
Amygdala/metabolism Androgen Antagonists/pharmacology Animals Anxiety/genetics Behavior, Animal Brain/metabolism Epigenesis, Genetic Female Germ Cells/metabolism Hippocampus/metabolism Male Oxazoles/pharmacology Rats Signal Transduction Transcription, Genetic
Chemicals
Androgen Antagonists Oxazoles vinclozolin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Skinner Michael K
Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington, USA. [email protected]
Anway Matthew D
Savenkova Marina I
Gore Andrea C
Crews David
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0003745
Email
[email protected]
Published
2008-00-00
Epub
2008-00-18
Pages
e3745
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC2581440
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0003745 PMC Full Text View journal details
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