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Edited by Fred H. Gage, The Salk Institute, San Diego, CA, and approved April 18, 2012 (received for review November 15, 2011)
Abstract
Ancestral environmental exposures have previously been shown to promote epigenetic transgenerational inheritance and influence all aspects of an individual’s life history. In addition, proximate life events such as chronic stress have documented effects on the development of physiological, neural, and behavioral phenotypes in adulthood. We used a systems biology approach to investigate in male rats the interaction of the ancestral modifications carried transgenerationally in the germ line and the proximate modifications involving chronic restraint stress during adolescence. We find that a single exposure to a common-use fungicide (vinclozolin) three generations removed alters the physiology, behavior, metabolic activity, and transcriptome in discrete brain nuclei in descendant males, causing them to respond differently to chronic restraint stress. This alteration of baseline brain development promotes a change in neural genomic activity that correlates with changes in physiology and behavior, revealing the interaction of genetics, environment, and epigenetic transgenerational inheritance in the shaping of the adult phenotype. This is an important demonstration in an animal that ancestral exposure to an environmental compound modifies how descendants of these progenitor individuals perceive and respond to a stress challenge experienced during their own life history.
Footnotes
↵1D.C. and M.K.S. contributed equally to this work.
- ↵2To whom correspondence may be addressed. E-mail: crews{at}mail.utexas.edu or skinner{at}wsu.edu.
Author contributions: D.C. and M.K.S. designed research; R.G., M.M., and M.I.S. performed research; D.C., R.G., S.V.S., M.M., M.I.S., and M.K.S. analyzed data; and D.C., R.G., S.V.S., M.M., M.I.S., and M.K.S. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Data deposition: All microarray CEL files reported in this study have been deposited in the Gene Expression Omnibus (GEO) database, www.ncbi.nlm.nih.gov/geo (accession no. GSE26737).
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1118514109/-/DCSupplemental.
Freely available online through the PNAS open access option.
Epigenetic transgenerational stress response
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