Zika Infection Shrinks Testicles in Mice

Study authors unsure if virus can harm human fertility

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HealthDay Reporter

WEDNESDAY, Feb. 22, 2017 (HealthDay News) -- Zika virus can be sexually transmitted through semen, and a new mouse study could help explain why that occurs -- and how the virus might damage male fertility.

In lab research, Zika attacked the testicles of mice, targeting cells that produce the male hormone testosterone and ultimately causing testes to shrink, the researchers said.

These findings "explain the persistence of the virus in semen," said Dr. Amesh Adalja.

"If these findings hold in humans, the long-term consequences could include diminished fertility in males who were infected with Zika," said Adalja, an affiliated scholar at the Johns Hopkins Center for Health Security in Baltimore. He was not involved in the study.

Zika typically is transmitted via mosquito bites, but researchers have learned that the virus also can be transmitted through a man's semen. As a result, the U.S. Centers for Disease Control and Prevention advises male Zika patients to use a condom during sex for at least six months following infection.

The Zika epidemic began nearly two years ago in Brazil. It has since spread throughout South and Central America and the Caribbean, causing severe birth defects in thousands of babies born to women infected with the virus during pregnancy.

The most common birth defect has been microcephaly, which causes an abnormally small head and brain. More subtle sensory and neurological problems have surfaced as doctors study these babies for longer periods of time.

Because Zika can be transmitted through semen, researchers hypothesized that the virus might replicate in the testicles, said lead study author Ryuta Uraki. He's a postdoctoral associate with the Yale University School of Medicine in New Haven, Conn.

To test this, Uraki and his colleagues infected male mice with Zika and monitored the virus' presence in different cell types.

They found that even after Zika disappeared from the blood, the virus continued to replicate in testicular cells called Leydig cells, which produce testosterone.

The researchers also found high levels of Zika genetic material in the epididymis, a narrow tube that helps deliver freshly produced sperm into the male's seminal fluid.

"We found that Zika virus infection is able to replicate in the testes, and in doing so causes inflammation and decreases testosterone levels in infected mice," Uraki said.

After 21 days, the testicles of Zika-infected mice had become significantly smaller than those of uninfected control mice, indicating progressive testicular atrophy, the researchers reported.

The testicular atrophy could be explained a couple of ways, Uraki said.

Zika infection might produce an immune response that attacks the testicles and causes them to shrink, he said. Or, Zika's attack on Leydig cells could prompt such a reduction in testosterone levels that the testicles become smaller, he suggested.

In either case, it's likely that Zika infection harmed the fertility of these mice, Uraki said.

"Testicular atrophy indicates that cells in the testes have died after Zika virus infection, which could include sperm cells, leading to a decrease in the fertility of the mouse," he said.

Other studies have shown that Zika-affected sperm tend to display reduced movement, which affects fertility.

It's possible that Zika has the same effect on human males, Uraki said. However, results of animal studies aren't necessarily replicated in humans.

"It has been reported that Zika virus was detected in semen of infected men for prolonged periods of time, which does indicate that there is replication of the virus in the testes," Uraki said.

"It would be interesting to track the testosterone levels of men infected with [Zika] to determine if the virus affects humans similarly to our mouse model," he added.

Other questions remain unanswered, too, Uraki said. Among them: How is Zika virus capable of persisting in the testes?

"We are also interested in determining if the testicular atrophy we observed is reversible after the virus is finally cleared, and what the long-term implications might be on the fertility of these mice," he said.

Adalja said the mouse study "illustrates another new aspect" of this dangerous virus.

"It will be crucial to understand if this phenomenon occurs in humans and underscores the need for a Zika vaccine," Adalja concluded.

The study results appear in the Feb. 22 issue of the journal Science Advances.

More information

For more about sexual transmission of Zika, visit the U.S. Centers for Disease Control and Prevention.

SOURCES: Ryuta Uraki, Ph.D., postdoctoral associate, Yale University School of Medicine, New Haven, Conn.; Amesh Adalja, M.D., affiliated scholar, Johns Hopkins Center for Health Security, Baltimore; Science Advances, Feb. 22, 2017

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