Fall 2012

Nervous Dads, Anxious Daughters

Male mice exposed to chronic social stress early in life produce anxiety-ridden female offspring

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Stressed-out male mice may produce anxiety-ridden daughters. Photo: Photo Researchers Inc.

A woman’s risk of anxiety and dysfunctional social behavior may depend on the experiences of her parents, particularly her dad, when they were young, according to a study in mice conducted by researchers at Tufts School of Medicine. The study, published online in Biological Psychiatry, suggests that stress caused by chronic social instability during youth contributes to epigenetic changes in sperm cells that can lead to psychiatric disorders in female offspring across multiple generations.

“The long-term effects of stress can be pernicious,” said the study’s lead author, Lorena Saavedra-Rodríguez, a postdoctoral fellow in the laboratory of Larry Feig, a professor of biochemistry. “We first found that adolescent mice exposed to chronic social instability, where the cage composition of mice is constantly changing, exhibited anxious behavior and poor social interactions through adulthood,” she said, noting, “these changes were especially prominent in female mice.”

The researchers then studied the offspring of these previously-stressed mice and observed that again female, but not male, offspring exhibited elevated anxiety and poor social interactions. Notably, even though the stressed males did not express any of these altered behaviors, they passed on these behaviors to their female offspring after being mated to nonstressed females. Moreover, the male offspring passed on these behaviors to yet another generation of female offspring.

“We are searching for biochemical changes in the sperm of stressed fathers that could account for this newly appreciated form of inheritance,” said Feig, who is also a member of the biochemistry and neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences. “Hopefully, this work will stimulate efforts to determine whether similar phenomena occur in humans.”

The research was funded by the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

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