Scientists probing potential problems for Zika-infected men today reported new findings in mice that reveal the virus can damage the male reproductive system, resulting in shrunken testicles, a drop in testosterone, and reduced fertility.
In other Zika developments, Puerto Rico reported its first baby born with microcephaly linked to the virus, officials in Ontario reported Canada's first known detection of Aedes aegypti mosquitoes, and Vietnam reported a dozen more illnesses, all from the country's largest city.
Testicular damage, sex hormone decreases
Though most of the worries about Zika virus have been related to birth defects that occur after a pregnant woman passes the virus to her fetus, little is known about harmful consequences to men, though the virus has been known to persist in semen for as long as 6 months.
To search for possible clues, a research team from Washington University School of Medicine injected male mice with Zika virus and monitored their reproductive system function and other parameters over the next 6 weeks. They reported their findings today in a letter to Nature.
The investigators injected the animals with either a mouse-adapted African Zika virus strain or the closely related dengue virus. Persistence in the testes and epididymis of mice was seen only with Zika virus, which migrated to the testes 1 week after infection with signs of inflammation seen on microscopic examination.
Two weeks later, researchers noticed that the testicles of the infected mice were significantly smaller, with internal structure collapse and dead or dying cells. At three weeks, mice testicles had shrunk to one tenth of normal size, and blood tests showed drops in sex hormone levels. At the 6-week mark, mice testicles showed no sign of healing, despite the fact that the animals had cleared the virus from their systems.
Michael Diamond, MD, PhD, one of the study's senior authors and professor of medicine at Washington University School of Medicine, said in a press release that it's not clear if the findings in mice will translate to humans. But the findings do hint that men might experience low testosterone levels and low sperm counts after Zika infection, which would affect fertility, he added.
"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.
The researchers found that Zika infects and kills Sertoli cells, located at the barrier between the bloodstream and the testes where they nourish developing sperm cells. They noted that Sertoli cells don't regenerate.
As mice testes sustained increasing damage, their sperm counts and testosterone levels fell. Six weeks after the mice were infected, the team found that the number of motile sperm had dropped tenfold, with testosterone levels that were also low.
When the team paired healthy female mice with infected and uninfected males, the females paired with the infected mice were four times less likely to become pregnant.
Kelle Moley, MD, a fertility specialist at the university and one of the paper's senior authors, said in the press release, "This is the only virus I know of that causes such severe symptoms of infertility. There are very few microbes that can cross the barrier that separates the testes from the bloodstream to infect the testes directly."
Complications in men on the clinical radar
So far no reports have been published linking infertility to Zika infection in men, but Moley said infertility can be difficult to detect in epidemiologic surveys.
People often don't know they're infertile until they try to have children, which could be years or even decades after infections, Moley said. "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."
However, symptoms of low testosterone—which include low sex drive, erectile dysfunction, fatigue, and low amounts of body hair and muscle mass—might be a more timely, telltale sign, she added. "If testosterone levels drop in men like they did in 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."
So far it's not clear how the dramatic testicle shrinkage the team saw in mice would compare with what happens in humans, Moley added.
Diamond said the findings raise several more questions about complications in men and how often they happen. "We don't know what proportion of infected men get persistently infected, or whether shorter-term infections can also have consequences for sperm count and fertility. These are things we need to know."
Microcephaly, Aedes, Vietnam news
- Puerto Rico on Oct 28 announced its first baby born with Zika-related microcephaly, according to an Associated Press report that cited Ana Rius, MD, the territory's health secretary. The baby was born within the past 2 weeks and is hospitalized with severe brain defects, along with vision and hearing problems. The mother is from San Juan, and health officials are monitoring about 2,400 pregnant women who have been infected with the virus.
- Health officials in Windsor, Ontario, announced the detection of Ae aegypti mosquitoes, apparently the first discovery in Canada, according to an Oct 28 statement from the Windsor-Essex County Health Unit. Authorities found the larvae during enhanced surveillance of Ae albopictus mosquitoes. It's not known how the larvae arrived in Ontario, but they could have come from the United States in shipping containers, cross-border vehicle transport, or in tires or other recycled products. The health department said extremely hot summer temperatures allowed the species to exist, but it won't likely survive cold winter temperatures.
- Vietnam today confirmed 12 more Zika infections, lifting the country's total to 23, Xinhua, China's state news agency, reported. All of the new cases were in Ho Chi Minh City.
See also:
Oct 31 Nature letter
Oct 31 Washington University School of Medicine press release
