Not only did male mice infected with the Zika virus have a tougher time getting females pregnant, their levels of sex hormones crashed, and their testicles shrunk by 90%, possibly permanently, according to new researchby the Washington University School of Medicine in St. Louis.
Of course, these are mice, not men.
"We undertook this study to understand the consequences of Zika virus infection in males," said co-senior author Dr. Michael Diamond, associate director of the school's Center for Human Immunology and Immunotherapy Programs.
"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."
"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," added co-senior author Dr. Kelle Moley, professor of obstetrics and gynecology at the Washington University School of Medicine. "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."
Zika's effect on men
It's well-known that Zika can survive in the testes of some men long after the virus has cleared their blood and urine. One man harbored live virus in his testes for three months, and traces of the RNA that makes up Zika has been found in other men's sexual organs for up to six months. That's why both the Centers for Disease Control and Prevention and the World Health Organization have told men who have traveled to an area where Zika is active to use condoms for a full six months after exposure.
Not only does Zika live and grow in some men's testes, but the viral load can continue to climb to a level much higher than was originally found at the time of infection. The question no one can yet answer: What does that do to a man's sexual organs and performance?
"Of course, a mouse is not human," said Sujan Shresta, an associate professor at the La Jolla Institute for Allergy and Immunization. "But there has to be some aspects of this virus interacting with a mammalian host that we can take away from this type of research.
"The last thing I want to do is scare people, but I can imagine as a scientist if the virus is always replicating, then chances are that it is destroying your sperm," Shresta added. "Eventually, that person will be infertile, right? And we don't know right now. We don't have the data."
No one knows how many men who get Zika might continue to harbor the virus in their testes. Studies are underway to figure that out.
"You have to have keep in the back of your mind that what's making it into publications are what are the exceptions, not the rules," said Dr. John Brooks, a medical epidemiologist at the CDC. "And we don't yet know with any kind of confidences, as far as I know, what is the average. Where do most people fall?"
"We are just now following people long enough to determine how long the virus can exist and in what proportion of men it can do that," said Dr. William Schaffner, medical director of the National Foundation for Infectious Diseases. "Is it 1%? 20? We just don't know."
Zika's effect on male mice
It didn't take long for the Zika virus to wreak havoc in the sexual organs of male mice. Within one week of infection, the virus arrived in the testes. Within two weeks, Sertoli cells were dead or dying, and the testes were already significantly smaller. Sertoli cells, which nourish developing sperm cells, are also responsible for keeping a blood-testes barrier in place to protect those new cells as they grow.
"There is a blood-testes barrier that immune cells don't normally cross unless something is very wrong," Diamond said. "And you don't want them to cross because you don't want to eliminate germ cells, which are going to propagate the species."
"There are very few microbes that can cross the barrier that separates the testes from the bloodstream to infect the testes directly," said Moley, who is also a fertility specialist and director of the university's Center for Reproductive Health Sciences.
The study found that Zika not only crossed that barrier, it attacked and destroyed the Sertoli cells, which do not regenerate.
At three weeks after infection, according to the study, the male mice's testicles were one-tenth of their normal size. The organs showed no signs of healing when examined at six weeks, even though the virus had long cleared the bloodstream. Sperm counts and levels of testosterone in the male mice also dropped tenfold.
"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," Diamond said.
Whether any of this damage will also occur in men is unknown, say the researchers, but it's worth studying in areas of the world with high rates of Zika infection, such as Central and South America.
"Wouldn't a man notice if his testicles shrank?" Moley asked. "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."
"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," Diamond said. "These are things we need to know."