Epigenetic transgenerational inheritance of altered stress responses

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 109; no. 23; pp. 9143 - 9148
• Main Authors: Crews, David, Gillette, Ross, Scarpino, Samuel V., Manikkam, Mohan, Savenkova, Marina I., Skinner, Michael K.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05-06-2012; National Acad Sciences
• Subjects: Age Factors; Amygdala; Analysis of Variance; Animals; Anxiety; Behavior, Animal - drug effects; Biological Sciences; Brain - growth & development; Brain - metabolism; Dyadic relations; Energy Metabolism - drug effects; Epigenesis, Genetic - physiology; Epigenetics; Fungicides, Industrial - toxicity; Gene Regulatory Networks - drug effects; Genes; Genetic inheritance; Genotype & phenotype; Hippocampus; Inheritance Patterns - genetics; Inheritance Patterns - physiology; Male; Male animals; Microarray Analysis; Oxazoles - toxicity; Phenotype; Phenotypes; Physiology; Principal Component Analysis; Rats; Restraint, Physical; Rodents; Stress; Stress, Physiological - physiology; Systems Biology - methods; Transcriptome - drug effects
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1118514109

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.