Third offspring later, chemical effects linger

The findings, published in the latest Proceedings of the National Academy of Sciences, put a new twist on the notions of nature and nurture, with broad implications for how certain behavioral tendencies, including responses to stress, might be inherited. The researchers—David Crews at the University of Texas at Austin, Michael Skinner at Washington State University, and colleagues—exposed gestating female rats to vinclozolin, a popular fruit and vegetable fungicide. The fungicide does not directly alter DNA but does causes changes in elements that regulate genes. This “epigenetic change” can be passed down to subsequent generations. The researchers put the rats’ third generation of offspring through a variety of behavioral tests and found they were more anxious, more sensitive to stress, and had greater activity in stress-related regions of the brain than descendants of unexposed rats. “We are now in the third human generation since the start of the chemical revolution, since humans have been exposed to these kinds of toxins,” says Crews, professor in the Section of Integrative Biology. “This is the animal model of that.” “The ancestral exposure of your great-grandmother alters your brain development to then respond to stress differently,” says Skinner, professor in the School of Biological Sciences. “We did not know a stress response could be programmed by your ancestors’ environmental exposures.” The researchers had already shown that exposure to vinclozolin can affect mate choice in later generations. The new research deepens their study of the epigenetics of the brain and behavior, dealing for the first time with real-life challenges such as stress. It also takes a rare, systems biology approach, looking at the brain from the molecular level to the physiological level to behavior. “We did not know a stress response could be reprogrammed by your ancestors’ environmental exposures,” says Skinner, who focused on the epigenetic transgenerational inheritance and genomics aspects of the paper. “So how well you socialize or how your anxiety levels respond to stress may be as much your ancestral epigenetic inheritance as your individual early life events.” Crews says that well-documented increases in mental disorders may be attributable to the kind of “two-hit” exposure that the experiment is modeling. “There is no doubt that we have been seeing real increases in mental disorders like autism and bipolar disorder,” says Crews, who focused on the neuroscience, behavior, and stress aspects of the paper. “It’s more than just a change in diagnostics. The question is: Why? Is it because we are living in a more frantic world, or because we are living in a more frantic world and are responding to that in a different way because we, or our ancestors, have been exposed to environmental contaminants. I favor the latter.” The researchers also saw intriguing differences in weight gain, opening the door to further research on obesity. The rats affected by their ancestors’ exposure to vinclozolin were significantly overweight compared with unexposed rats. Photo/credit iStockphoto