Zika Virus May Damage Fertility in Men

Human studies will determine if men are similarly affected.

Most of the research to understand the consequences of Zika virus infection has focused on how the virus affects pregnant women and causes severe birth defects in their developing fetuses. The new study in mice suggests that Zika infection may have major consequences for men by interfering with their ability to have children. The results showed that the virus targeted the male reproductive system: three weeks after male mice were infected with Zika, their testicles had shrunk, sex hormone levels had dropped, and fertility was reduced. Overall, these mice were less likely to impregnate female mice.

The virus is known to persist in men’s semen for months. The US Centers for Disease Control and Prevention (CDC) recommend that men who have traveled to a Zika-endemic region use condoms for 6 months, regardless of whether they have had symptoms of Zika infection. It is not known, however, what impact this lingering virus can have on men’s reproductive systems.

To find out how the Zika virus affects males, the research team, led by co-senior authors Michael Diamond, MD, PhD, and Kelle Moley, MD, both professors at Washington University School of Medicine (St. Louis, MO, USA), injected male mice with the Zika virus. After 1 week, the virus had migrated to the testes, which bore microscopic signs of inflammation. After 2 weeks, the testicles were significantly smaller, their internal structure was collapsing, and many cells were dead or dying.

After 3 weeks, the mice’s testicles had shrunk to 1/10th of normal size and the internal structure was completely destroyed. The mice were monitored until 6 weeks post-infection, and in that time their testicles did not heal – even after the mice had cleared the virus from their bloodstreams.

“We don’t know for certain if the damage is irreversible, but I expect so, because the cells that hold the internal structure in place have been infected and destroyed,” said Prof. Diamond.

The structure of the testes depends Sertoli cells, which maintain the barrier between bloodstream and testes and nourish developing sperm cells. The researchers found that Zika infects and kills Sertoli cells, and Sertoli cells do not regenerate. Furthermore, as the mice’s testes sustained increasing levels of damage, their sperm counts and testosterone levels plummeted. By 6 weeks post-infection, the number of motile sperm was down 10-fold, and testosterone levels were similarly low.

When healthy females were mated with infected and uninfected males, the females paired with infected males were about 4 times less likely to become pregnant as those paired with uninfected males.

“This is the only virus I know of that causes such severe symptoms of infertility,” said Prof. Moley, “There are very few microbes that can cross the barrier that separates the testes from the bloodstream to infect the testes directly.”

No reports have been published linking infertility in men to Zika infection, but infertility can be a difficult symptom to pick up in epidemiologic surveys. “People often don’t find out that they’re infertile until they try to have children, and that could be years or decades after infection,” said Prof. Moley, “I think it is more likely doctors will start seeing men with symptoms of low testosterone, and they will work backward to make the connection to Zika.”

Low testosterone can be diagnosed with a simple blood test. “If testosterone levels drop in men like they did in the mice, I think we’ll start to see men coming forward saying, ‘I don’t feel like myself,’ and we’ll find out about it that way,” said Prof. Moley said, “You might also ask, ‘Wouldn’t a man notice if his testicles shrank?’ Well, probably. But we don’t really know how the severity in men might compare with the severity in mice. I assume that something is happening to the testes of men, but whether it’s as dramatic as in the mice is hard to say.”

Professors Diamond and Moley said human studies in areas with high rates of Zika infection are needed to help determine the impact of the virus on human male reproductive health. “The question is, what happens in men and at what frequency?” said Prof. Diamond, “We don’t know what proportion of infected men get persistently infected, or whether shorter-term infections also can have consequences for sperm count and fertility.”

The study, by Govero J et al, was published on October 31, 2016, in the journal Nature.

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Washington University School of Medicine