Sperm from Fathers With COVID-19 Passes Anxiety to Offspring

Infections in mice can cause altered sperm and increased anxiety in offspring.

In a Melbourne lab, researchers infected male mice with SARS-CoV-2, the virus that causes COVID-19. After the mice recovered, they were bred with healthy females. When their offspring grew up, the young mice were more anxious and less willing to explore.

The finding, published in Nature Communications by scientists at the Florey Institute of Neuroscience and Mental Health, suggests that a father’s encounter with the coronavirus could echo into the next generation—at least in mice.

“We found that the resulting offspring showed more anxious behaviours compared to offspring from uninfected fathers,” said first author Dr. Elizabeth Kleeman.

Anxious Pups

The researchers infected genetically modified mice that carry the human ACE2 receptor, the same molecular doorway the virus uses to invade human cells. The male mice experienced testicular inflammation and reduced sperm quality. But the most striking change was molecular: the infection altered the sperm’s small noncoding RNAs, or sncRNAs, molecules that help regulate gene expression during early development.

In healthy mice, these RNAs act like post-it notes attached to DNA, influencing which genes switch on or off. After the infection, those notes were rearranged.

“We already knew that when male mice were exposed to 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. “This is because the father’s experiences can alter the information carried in sperm, including specific RNA molecules, which transmit instructions for offspring development.”

To see if those molecular scars could shape the next generation, the team bred the recovered males with uninfected females. The pups never encountered the virus themselves. Yet they acted as if something inside them remembered it. Female offspring, in particular, showed altered activity in genes within the hippocampus—the brain region tied to emotion and memory.

Dr. Carolina Gubert, another senior author, explained that “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.”

Even In Vitro

The scientists went a step further. They extracted RNA from the sperm of infected males and injected it directly into fertilized mouse eggs. The offspring from these eggs (who had never been near the virus) developed the same anxious behaviors.

That experiment sealed the case: the virus had rewritten the sperm’s molecular messages, and those changes alone could influence brain development.

In total, the team identified six major RNA alterations, including changes in piRNAs and microRNAs, classes of molecules known to regulate genes linked to brain formation. Gene analysis showed the affected pathways involved “signaling pathways regulating pluripotency of stem cells,” suggesting that infection may influence early embryonic programming.

The effect seems to fade away in a few generations. The researchers bred the offspring (the F1 generation) and found subtle differences in their own young (the F2 generation)—slightly smaller litter sizes and altered body weights, but no clear anxiety traits. The effects, it seems, faded with each generation.

Still, even transient changes are noteworthy. Epigenetic inheritance—the idea that experiences can modify genes’ activity and pass those modifications to offspring—has been seen with stress, malnutrition, and infections before. But this is the first evidence linking COVID-19 to such changes.

From Mice to Men

Could the same thing happen in humans? The researchers are cautious to draw any definite conclusions..

“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,” said Professor Hannan.

No human data yet show that infection alters sperm in this way. The mice in the study were exposed to high doses of the virus, and their immune systems differ from ours. But the idea that severe infection might leave molecular marks in reproductive cells raises questions that researchers are only beginning to explore.

COVID-19 has already reshaped society in ways that extend beyond the body count: long-term illness, disrupted education, and mental health scars that persist years after lockdowns. Now, this mouse study hints at another layer—one embedded in biology itself.

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“If our findings translate to humans,” Hannan warned, “this could impact millions of children worldwide, and their families, with major implications for public health.”

For now, those implications remain theoretical. But as scientists probe the enduring aftermath of the pandemic, studies like this one remind us that viruses can ripple through generations in ways we’re only beginning to understand.