Does Zika Harm Male Fertility?

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Feb. 22, 2017 — Researchers at the CDC are working with a fertility clinic in Puerto Rico, which has been hard-hit by Zika, to determine if men infected by the virus have lower sperm counts or sperm that doesn’t work as well in the weeks and months after infection.

That study got underway just last month and so far has enrolled just a handful of men. It generally takes about 90 days for a man to produce sperm, so researchers are planning to track them for at least 6 months to assess any changes.

“It’s going to be important for us to follow them up for several months to rule in or rule out any effects of Zika infection,” says Tyler Sharp, PhD, chief epidemiologist at the CDC’s Dengue Branch in San Juan, Puerto Rico.

The reason why they’re worried is that in recent months, three separate studies have documented the grave damage the Zika virus can do to the male testes, at least in mice.

“It just looks like it’s been destroyed,” says Kelle Moley, MD, co-director of the Institute of Clinical and Translational Sciences at Washington University in St. Louis. “As a result, you’re left with a testis that’s about a tenth of the size of a normal, non-infected testis.” Moley has documented the same phenomenon in mice, but was not involved in the current study.


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The newest study, released Wednesday by a team at Yale and the Howard Hughes Medical Institute, found that Zika attacked specialized cells called Leydig cells that produce the hormone testosterone and support sperm production. About 3 weeks after infection, the mouse testes were much smaller than those of mice that were not infected, and they had far less testosterone in their blood.

The studies raise the possibility that Zika infection may have lasting impacts on men. The virus is already known for causing birth defects in developing babies.

“No one has really correlated this to infertility in men,” Moley says, “but infertility is not something that comes to the forefront when you have a cold. No one is going to get a semen analysis on someone who has a fever and a rash and chills. We may not know if people are infertile because of Zika for 20 or 30 years.”

A rash, fever, and chills are among the symptoms of Zika.

In addition to being nerve-loving, or neurotropic, the Zika virus also seems to gravitate to the reproductive tract. Researchers have documented that the infection can be passed sexually, as well as through the bite of an infected mosquito.

Sharp’s team reported just last week that Zika persists in the semen of some men for months.

Sharp says that so far, he has not heard any case reports from Brazil or other countries with widespread Zika outbreaks of reproductive effects or shrinkage of the testes in men. He says he is skeptical that what’s happening in mice is also happening to people.

He says typically, when scientists use mice to study disease, it’s because they see an effect in humans and want to study it more closely in an animal model.

“What appears to have happened now is the opposite of that. We have [observable effects] in a mouse model, and now we’re seeing if we can find it in humans. That doesn’t mean that it doesn’t exist, but typically it’s the opposite order,” he says.

Moley agrees with Sharp that her findings need to be confirmed in men.

“I think it needs to be studied at a population level, and I think that’s what the CDC is trying to do,” she says.

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Moley and her colleagues watched what happened to the male reproductive systems in mice in the weeks after infection with the Zika virus. They found that the virus attacks cells that are responsible for building a barrier between sperm and blood. This barrier is critical because it hides the sperm from attack by the body’s own immune system. When the barrier is breached, the immune system comes in, and by about 21 days after infection, Moley says, very little of the internal architecture of the testes is left.

The mice in her study, which was published last October, had lowered sperm counts, lower testosterone, and were far less likely to impregnate female mice.

The study out Wednesday found the same outcome, though the researchers think the testes shrink because Zika makes a direct attack on Leydig cells, slashing the production of testosterone.

Ryuta Uraki, PhD, a postdoctoral researcher at Yale, says other questions remain, like whether the testes can recover after a Zika infection.

“We want to examine whether damage in the testes can be reversed after the virus is cleared and fertility can be restored,” he says.

Sources

SOURCES:

Kelle H. Moley, MD, co-director of the Institute of Clinical and Translational Sciences at Washington University in St. Louis, Mo.

Tyler Sharp, PhD, chief epidemiologist at the CDC’s Dengue Branch in San Juan, Puerto Rico

Ryuta Uraki, PhD, post doctoral researcher, Yale University, New Haven, Conn.

Science Advances, Feb. 22, 2017

Nature, Oct. 31, 2017

The Canadian Journal of Hospital Pharmacy: “Zika Virus: Facts, Prevention Strategies, and an Informed Tourist Perspective.”


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