Trans generational Epigenetic Programming of the Brain Transcriptome and Anxiety

Behavior

Michael K. Skinner 1, Matthew D. Anway 1, Marina I. Savenkova 1, Andrea C. Gore

2, David Crews 3



1 Center for Reproductive Biology, School of Molecular Biosciences, Washington

State University, Pullman, Washington, United States of America,

2 Division of Pharmacology and Toxicology, University of Texas, Austin, Texas,

United States of America,

3 Section of Integrative Biology, University of Texas, Austin, Texas, United

States of America



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.



Source: PLoS One [Open Access]

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0003745



Posted by

Robert Karl Stonjek