Male Mice Exposed to Chronic Social Stress Have Anxious Female Offspring
Tufts University Press Release
BOSTON — A study in mice conducted by researchers at Tufts University School of Medicine suggests that a woman’s risk of anxiety and dysfunctional social behavior may depend on the experiences of her parents, particularly fathers, when they were young. 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. 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. These changes were especially prominent in female mice,” said first author Lorena Saavedra-Rodríguez, Ph.D., postdoctoral fellow in the Larry Feig laboratory at Tufts University School of Medicine.
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 non-stressed females. Moreover, the male offspring passed on these behaviors to yet another generation of female offspring.
“We are presently searching for biochemical changes in the sperm of stressed fathers that could account for this newly appreciated form of inheritance” said senior author Larry A. Feig, Ph.D., professor of biochemistry at Tufts University School of Medicine and member of the biochemistry and neuroscience program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts University. “Hopefully, this work will stimulate efforts to determine whether similar phenomena occur in humans.”
This research was supported by award numbers AA019317 from the National Institute on Alcohol Abuse and Alcoholism, and MH083324 from the National Institute of Mental Health, both part of the National Institutes of Health (NIH). The research was also supported by award number NS047243 from National Institute of Neurological Disorders and Stroke (NIH) to the Tufts Center for Neuroscience Research.
Saavedra-Rodríguez L, Feig LA. Biological Psychiatry. “Chronic Social Instability Induces Anxiety and Defective Social Interactions Across Generations.” Available online August 20, 2012. http://dx.doi.org/10.1016/j.biopsych.2012.06.035
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Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts University are international leaders in innovative medical education and advanced research. The School of Medicine and the Sackler School are renowned for excellence in education in general medicine, biomedical sciences, special combined degree programs in business, health management, public health, bioengineering and international relations, as well as basic and clinical research at the cellular and molecular level. Ranked among the top in the nation, the School of Medicine is affiliated with six major teaching hospitals and more than 30 health care facilities. Tufts University School of Medicine and the Sackler School undertake research that is consistently rated among the highest in the nation for its effect on the advancement of medical science.
EFFECTS OF PRENATAL STRESS PASSED ACROSS GENERATIONS IN MICE
News Release –
Study identifies changes in brain that might contribute to individual differences in behavior
Washington, DC — Sons of male mice exposed to prenatal stress are more sensitive to stress as adults, according to a study in the August 17 issue of The Journal of Neuroscience. These findings suggest experiences in the womb can lead to individual differences in stress response that may be passed across generations.
Tracy Bale, PhD, of the University of Pennsylvania, and colleagues previously found that male mice were sensitive to stress their mothers experienced during pregnancy. In the current study Bale, together with Chris Morgan, also of the University of Pennsylvania, bred those stress-sensitive males with normal females to see if the heightened stress response could be transmitted to the next generation of mice. Even though the male offspring had no additional exposure to stress in the womb, they displayed a more pronounced reaction to stress, just like their fathers.
“This study shows that the effects of maternal stress in mice are passed by the sons to the grandsons of the stressed mothers,” said Arthur Arnold, PhD, an expert on sex differences in the brain at the University of California, Los Angeles. “Since male mice are not involved in rearing the offspring in the lab setting, the findings suggest that the transmission of the trait from son to grandson is through the son’s DNA,” added Arnold, who was unaffiliated with the study.
In general, female mice tend to respond more to stress than do males. However, in the current study, the sons and grandsons of female mice that were stressed while pregnant showed a stress response more similar to female mice.
Compared with other male mice, the stress-sensitive grandsons also had smaller testes, as did their fathers, suggesting they were exposed to less testosterone around birth — a critical period for establishing sex differences in the brain. Additionally, genes involved in brain development were turned on and off in a pattern more similar to female than male mice.
“Together these findings suggest prenatal stress may disrupt masculinization of the developing mouse brain,” Bale said. Although such changes did not deter the stress-sensitive male mice from reproducing, the results suggest exposure to stress during early pregnancy can lead to long-term changes in offspring that can be passed across generations.
The research was supported by the National Institute of Mental Health.