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Study Identifies Biological Mechanism by which Stress Alters Sperm and Impacts Brain Development in Next Generation

Prolonged fear and anxiety brought on by major stressors, like the coronavirus pandemic, can not only take a toll on a person鈥檚 mental health, but may also have a lasting impact on a man鈥檚 sperm composition that could affect his future offspring. That is the finding of a provocative new study published in the journal  by researchers at the University of Maryland School of BOB体育.

The research outlines a biological mechanism for how a father鈥檚 experience with stress can influence fetal brain development in the womb. The effects of paternal stress can be transferred to offspring through changes in the extracellular vesicles that then interact with maturing sperm. Extracellular vesicles are small membrane-bound particles that transport proteins, lipids, and nucleic acids between cells. They are produced in large amounts in the reproductive tract and play an integral role in sperm maturation.

鈥淭here are so many reasons that reducing stress is beneficial especially now when our stress levels are chronically elevated and will remain so for the next few months,鈥� said study corresponding author Tracy Bale, PhD, Professor of Pharmacology and Director of the Center for Epigenetic Research in Child Health & Brain Development at the University of Maryland School of BOB体育. 鈥淧roperly managing stress can not only improve mental health and other stress-related ailments, but it can also help reduce the potential lasting impact on the reproductive system that could impact future generations.鈥�

She and her colleagues did not specifically study those who were under stress due to the coronavirus pandemic.

To examine a novel biological role for extracellular vesicles in transferring dad鈥檚 stress to sperm, the researchers examined extracellular vesicles from mice following treatment with the stress hormone corticosterone. After treatment, the extracellular vesicles showed dramatic changes in their overall size as well as their protein and small RNA content.

When sperm were incubated with these previously 鈥渟tressed鈥� extracellular vesicles prior to fertilizing an egg, the resulting mouse pups showed significant changes in patterns of early brain development, and as adults these mice were also significantly different than controls for how they responded to stress themselves.

To see if similar differences occurred in human sperm, the researchers recruited students from the University of Pennsylvania to donate sperm each month for six months, and complete questionnaires about their perceived stress state in the preceding month. They found that students who had experienced elevated stress in months prior showed significant changes in the small RNA content of their sperm, while those who had no change in stress levels experienced little or no change. These data confirm a very similar pattern found in the mouse study. 

鈥淥ur study shows that the baby鈥檚 brain develops differently if the father experienced a chronic period of stress before conception, but we still do not know the implications of these differences,鈥� said Dr. Bale. 鈥淐ould this prolonged higher level of stress raise the risk for mental health issues in future offspring, or could experiencing stress and managing it well help to promote stress resilience? We don鈥檛 really know at this point, but our data highlight why further studies are necessary.鈥�

The research team did find that stress-induced changes in the male reproductive system take place at least a month after the stress is attenuated and life has resumed its normal patterns. 鈥淚t appears the body鈥檚 adaptation to stress is to return to a new baseline,鈥� Dr. Bale said, 鈥渁 post-stress physiological state 鈥� termed allostasis.鈥�

This research was funded by the National Institute of Mental Health and included co-authors from the Institute for Genome Sciences at the University of Maryland School of BOB体育 and the Department of Pharmaceutical Science at the University of Maryland School of Pharmacy, as well as the University of Pennsylvania.

鈥淭his research represents a critical step in understanding important mechanisms that underlie the field of intergenerational epigenetics,鈥� said UMSOM Dean E. Albert Reece, MD, PhD, MBA, who is also the Executive Vice President for Medical Affairs, University of Maryland, and the John Z. and Akiko K. Bowers Distinguished Professor. 鈥淪uch knowledge is crucial to identify early interventions to improve reproduction and early childhood development down the road.鈥�

While the study did not test stress management interventions to determine what effects they might have on attenuating the changes in sperm composition, Dr. Bale, who goes for regular runs to reduce the stress of the current COVID-19 pandemic, contends that any lifestyle habits that are good for the brain are likely good for the reproductive system.

鈥淚t is important to realize that social distancing does not have to mean social isolation, especially with modern technologies available to many of us,鈥� said Joshua Gordon, Director of the National Institute of Mental Health in his  about coping with coronavirus. 鈥淐onnecting with our friends and loved ones, whether by high tech means or through simple phone calls, can help us maintain ties during stressful days ahead and will give us strength to weather this difficult passage.鈥�

The  has tips on 鈥渟tress and coping鈥� page on their COVID-19 site that recommends the following to 鈥渟upport yourself鈥�:

• Take breaks from watching, reading, or listening to news stories, including social media. Hearing about the pandemic repeatedly can be upsetting.
• Take care of your body. Take deep breaths, stretch, or meditate. Try to eat healthy, well-balanced meals, exercise regularly, get plenty of sleep, and avoid alcohol and drugs.
• Make time to unwind. Try to do some other activities you enjoy.
• Connect with others. Talk with people you trust about your concerns and how you are feeling.

About the University of Maryland School of BOB体育

Now in its third century, the University of Maryland School of BOB体育 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 45 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 BOB体育 and the National Academy of Sciences, and a distinguished two-time winner of the Albert E. Lasker Award in Medical Research.  With an operating budget of more than $1.2 billion, the School of BOB体育 works closely in partnership with the University of Maryland Medical Center and Medical System to provide research-intensive, academic and clinically based care for nearly 2 million patients each year. The School of BOB体育 has more than $540 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 BOB体育 has a total population of nearly 9,000 faculty and staff, including 2,500 student trainees, residents, and fellows. The combined School of BOB体育 and Medical System (鈥淯niversity of Maryland BOB体育鈥�) has an annual budget of nearly $6 billion and an economic impact more than $15 billion on the state and local community. The School of BOB体育 faculty, which ranks as the 8th highest among public medical schools in research productivity, is an innovator in translational medicine, with 600 active patents and 24 start-up companies. The School of BOB体育 works locally, nationally, and globally, with research and treatment facilities in 36 countries around the world. Visit medschool.umaryland.edu