March 01, 2018 | David Kohn
Researchers Unravel Crucial Genetic Mechanisms Behind This Process.
New research in mice has found that a father’s stress affects the brain development of his offspring. This stress changes the father’s sperm, which can then alter the brain development of the child. This new research provides a much better understanding of the key role that fathers play in the brain development of offspring.
Scientists have known that a mother’s environment during pregnancy, including factors such as poor diet, stress or infection, can cause damage negatively impact her offspring. This may be due in part to how this environment affects the expression of certain genes — known as epigenetics.
Now, the researchers, led by neuroscientist Tracy Bale, MD, a professor in the University of Maryland School of Medicine (UMSOM) department of pharmacology and director of the UMSOM Center for Epigenetic Research in Child Health and Brain Development, show that a father’s stress can also affect offspring development, by altering important aspects of his sperm.
“These results offer really intriguing insight into how fathers’ stress can have significant effects on their offspring,” she said. “We now know much more about the mechanisms through which this process takes place. We have a lot to learn, particularly about how this process occurs in humans. We are now in the middle of a human study to see how this may work in men.”
Bale discussed this new, not-yet-published work at a special session and press conference at the 2018 AAAS annual meeting in Austin, Texas last month.
Previously, Dr. Bale had found that adult male mice experiencing chronic periods of mild stress have offspring with a reduced response to stress; changes in stress reactivity have been linked to some neuropsychiatric disorders, including depression and PTSD. She and her colleagues isolated the mechanism of the reduced response; they found that the father’s sperm showed changes in genetic material known as microRNA. MicroRNA are important because they play a key role in which genes become functional proteins.
Now, Dr. Bale and her colleagues have unraveled new details about these microRNA changes. In the male reproductive tract, the caput epididymis, the structure where sperm matures, releases tiny vesicles packed with microRNA that can fuse with sperm to change its cargo delivered to the egg. The caput epididymis responded to the father’s stress by altering the content of these vesicles.
This suggests that even mild environmental challenges can have a significant impact on the development and potentially the health of future offspring. By learning more about links between a father’s exposure to stress and the risks of disease for his offspring, we can better understand, detect, and prevent these disorders.
Bale has focused much of her research on the links between stress and subsequent risk for neurodevelopmental disorders, including autism and schizophrenia, in offspring. Her previous studies on the placenta have revealed novel sex differences during pregnancy that may predict increased prenatal risk for neurodevelopmental disorders in males.
“In recent years, we have realized that epigenetics plays a crucial role in so many aspects of health and disease, including brain development,” said E. Albert Reece, MD, PhD, MBA, Executive Vice President for Medical Affairs at UM Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “This new paper opens up exciting new avenues in this area, which will eventually enable us to come to a better understanding of the complex ways in which parental physiology affects offspring.”
About the University of Maryland School of Medicine
Commemorating its 210th Anniversary, the University of Maryland School of Medicine was chartered in 1807 as the first public medical school in the United States. It continues today as one of the fastest growing, top-tier biomedical research enterprises in the world -- with 43 academic departments, centers, institutes, and programs; and a faculty of more than 3,000 physicians, scientists, and allied health professionals, including members of the National Academy of Medicine and the National Academy of Sciences, and a distinguished recipient of the Albert E. Lasker Award in Medical Research. With an operating budget of more than $1 billion, the School of Medicine works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically-based care for more than 1.2 million patients each year. The School has over 2,500 students, residents, and fellows, and nearly $450 million in extramural funding, with most of its academic departments highly ranked among all medical schools in the nation in research funding. As one of the seven professional schools that make up the University of Maryland Baltimore campus, the School of Medicine has a total workforce of nearly 7,000 individuals. The combined School and Medical System (“University of Maryland Medicine”) has an annual budget of nearly $6 billion and an economic impact in excess of $15 billion on the state and local community. The School of Medicine faculty, which ranks as the 8th-highest public medical school in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu/
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