Washington University
in St. Louis
 |
| The testicles of male mice showed cellular damage and shrinkage three weeks after Zika infection. On the left is a healthy mouse testicle; on the right, a testicle following Zika infection. Credit: Prabagaran Esakky |
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.
But a new study in
mice suggests that Zika infection also may have worrisome consequences for men
that interfere with their ability to have children.
The research indicates that
the virus targets the male reproductive system.
Three weeks after male mice were
infected with Zika, their testicles had shrunk, levels of their sex hormones
had dropped and their fertility was reduced. Overall, these mice were less
likely to impregnate female mice.
The study is published
Oct. 31 in Nature.
The virus is known to
persist in men's semen for months. The Centers for Disease Control and
Prevention recommend that men who have traveled to a Zika-endemic region use
condoms for six 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, Diamond, co-senior author Kelle Moley, MD, the James
P. Crane Professor of Obstetrics and Gynecology, and colleagues injected male
mice with the Zika virus.
After one week, the virus had migrated to the testes,
which bore microscopic signs of inflammation. After two weeks, the testicles
were significantly smaller, their internal structure was collapsing, and many
cells were dead or dying.
After three 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 six 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," said Diamond, who is also a professor of pathology and
immunology, and of molecular microbiology.
The structure of the
testes depends on a type of cell called Sertoli cells, which maintain the
barrier between the bloodstream and the testes and nourish developing sperm
cells. Zika infects and kills Sertoli cells, the researchers found, and Sertoli
cells don't regenerate.
The testes normally
produce sperm and testosterone, and as the mice's testes sustained increasing
levels of damage, their sperm counts and testosterone levels plummeted. By six
weeks after infection, the number of motile sperm was down tenfold, and
testosterone levels were similarly low.
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," said
Moley, a fertility specialist 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 linking infertility in men to Zika infection, but, Moley said,
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," 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."
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."
Diamond and Moley said
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?" Diamond said. "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."