A new study suggests that a father’s COVID-19 infection could do more than make him sick – it may leave marks on his sperm that pass anxiety to his offspring, revealing how viral infections can echo across generations.
The COVID-19 pandemic has had, and continues to have, a significant impact on the world, especially in the fields of medicine and science. Researchers have looked extensively at SARS-CoV-2’s impact on disease risk and the health implications of long COVID.
In a new study led by The Florey Institute of Neuroscience and Mental Health (The Florey), researchers have discovered that a SARS-CoV-2 infection in male mice can alter their sperm, leading to changes in an offspring’s brain and behavior.
“We already knew that when male mice were exposed to specific environmental and lifestyle factors, like poor diet before mating, it could change brain development and behavior in offspring,” said co-corresponding author Professor Anthony Hannan, PhD, head of The Florey’s Epigenetics and Neural Plasticity Research Group. “This is because the father’s experiences can alter the information carried in sperm, including specific RNA molecules, which transmit instructions for offspring development.”
The researchers infected genetically modified mice that carry the human ACE2 receptor, which allows SARS-CoV-2 to enter cells much as it does in humans. The team then examined how the virus affected the males’ reproductive system and whether those changes could influence their offspring.
Infection caused clear signs of testicular inflammation and reduced sperm quality. The sperm count and motility dropped, and microscopic analysis revealed damage to the seminiferous tubules, where sperm are formed. Immune cells also invaded the testes, and inflammatory genes were switched on, indicating that the infection triggered an immune response in an organ that’s usually protected from such activity.
To test whether these sperm changes had lasting consequences, the infected male mice were bred with healthy, uninfected females. Their offspring were raised in identical, virus-free conditions, meaning any differences could only come from the father’s infection. When these young mice, particularly the females, were tested, they showed increased anxiety-like behaviors, such as avoiding open spaces and reacting more strongly to stress. Importantly, these offspring didn’t show signs of viral infection themselves; the behavioral differences were traced back to changes in the fathers’ sperm.
Further analysis revealed that SARS-CoV-2 infection had altered small noncoding RNA molecules (sncRNAs) in sperm – epigenetic markers known to influence how genes are expressed in the next generation. These sncRNAs act like molecular switches, influencing which genes are turned on or off during early development. In other words, the virus didn’t change DNA sequences, but left molecular “scars” that carried information capable of shaping offspring development and behavior. Female offspring also had significant changes in specific gene activity in the brain’s hippocampus region, important for anxiety, depression and other affective behaviors.
“These kinds of changes in the hippocampus, as well as other brain regions, may contribute to the increased anxiety we observed in offspring, via epigenetic inheritance and altered brain development,” said corresponding author and The Florey research fellow, Carolina Gubert, PhD.
While the study was done in mice, it raises important questions about the longer-term, heritable effects of COVID-19 infection, particularly in men. However, the researchers caution that mice were infected with high viral doses and that their immune systems differ from ours.
There’s no evidence yet that COVID-19 causes similar effects in human children, but the findings open a new area of investigation into whether severe infections could leave molecular traces in sperm that influence future generations.
“While more research is needed, particularly in the sperm and offspring of humans infected with the SARS-CoV-2 virus, these findings suggest that the COVID-19 pandemic could have long-lasting effects on future generations,” Hannan said. “Our discoveries highlight the importance of understanding the impacts of this virus and infectious disease, not only on those directly infected, but also on their children who may be affected by their parents’ experience with COVID-19.
“If our findings translate to humans, this could impact millions of children worldwide, and their families, with major implications for public health,” he added.
The study was published in the journal Nature Communications.
Source: The Florey Institute of Neuroscience and Mental Health
