Research Studies Zika Infection May Affect Male Fertility

    While much of the recent news concerning Zika has been focused on how the virus affects pregnant women and can lead to severe birth defects, a new study from investigators at the Washington University School of Medicine (WUSM) has found evidence in mice that suggests Zika infections target the male reproductive system—interfering with their ability to produce offspring.

    “We undertook this study to understand the consequences of Zika virus infection in males,” explained co-senior study investigator Michael Diamond, M.D., Ph.D., professor of medicine, pathology, immunology, and molecular microbiology at WUSM. “While our study was in mice—and with the caveat that we don’t yet know whether Zika has the same effect in men—it does suggest that men might face low testosterone levels and low sperm counts after Zika infection, affecting their fertility.”

    The findings from this study were published recently in Nature in an article entitled “Zika Virus Infection Damages the Testes in Mice.”

    Previous research has revealed that the Zika virus can persist in men’s semen for months. Public health organizations like the Centers for Disease Control and Prevention recommend that men who have traveled to Zika-endemic regions use condoms for 6 months, regardless of whether they have had symptoms of Zika infection. Currently, it is unknown what impact this lingering virus can have on men’s reproductive systems.

    The WUSM researchers wanted to find out how Zika affected the male reproductive system and began by injecting mice with the 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 one-tenth their normal size and the internal structure was completely destroyed. The mice were monitored until 6 weeks, 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,” noted Dr. Diamond.

    The researchers found that the Zika virus preferentially infects and kills Sertoli cells, which help determine the structure of the testes and maintain the barrier between the bloodstream and the testes and nourish developing sperm cells. Unfortunately, Sertoli cells do not regenerate.

    While the testes typically produce sperm and testosterone, as the mice’s testes sustained increasing levels of damage, their sperm counts and testosterone levels plummeted. By 6 weeks after infection, the number of motile sperm was down 10-fold, and testosterone levels were similarly low. Additionally, when healthy females were mated with infected and uninfected male mice, the females paired with infected males were about four 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,” remarked co-senior study investigator Kelle Moley, M.D., professor of obstetrics and gynecology and director of the university’s Center for Reproductive Health Sciences. “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 yet 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,” Dr. Moley stated. “I think it is more likely doctors will start seeing men with symptoms of low testosterone, and they will work backward.

    Men with low testosterone may experience a low sex drive, erectile dysfunction, fatigue, and loss of body hair and muscle mass. 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,” 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.”

    The research team agreed that human studies in areas with high rates of Zika infection are needed to determine the impact of the virus on men’s reproductive health.

    “Now that we know what can happen in a mouse, the question is, what happens in men and at what frequency?” Dr. Diamond concluded. “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. These are things we need to know.”