Zika Now Implicated in Male Infertility Too

Virus caused testes to shrink by up to 80%, sperm count to fall - and the damage may be irreversible, mouse study shows.

A health ministry worker fumigates a house to kill mosquitoes during a campaign against dengue and chikungunya and to prevent Zika infection in Managua, Nicaragua October 27,2016.
Oswaldo Rivas, Reuters

The Zika virus may be causing adult male infertility, not only nervous system damage in newborns and adults. Infecting male mice with the virus caused severe testicular shrinkage and damage in most cases, and reduced sperm levels too, scientists warn in a paper published in Nature.

Moreover, the damage caused by the virus to the adult male reproductive system may be irreversible.

The finding reinforces warnings to avoid Zika-infested locations when planning pregnancy, insofar as possible – a rule that applies to both sexes.

Zika damage

The aftermath of Zika infection is becoming clearer and the news is all bad. The virus has been categorically associated with causing microcephaly and other birth defects in newborns by damaging nervous and brain tissue in utero. It has also turned out that Zika can cause nervous damage in adults as well: Most infected adults are either asymptomatic or develop mild flu-like symptoms, but a fast-growing number has been developing Guillain-Barré syndrome, which can cause paralysis that usually, but not always, passes.

Usually Zika is transmitted by mosquito. The discovery that in rare cases, it can be sexually transmitted spurred Dr. Michael Diamond of the Washington University School of Medicine, Missouri and his team to look for traces of the virus in testicle tissue. And indeed, earlier this year, they reported finding it.

These and other findings impelled the Centers for Disease Control to issue an unprecedented guideline earlier this year, urging people trying to conceive to wait six months after the man's confirmed or suspected infection with Zika. The latest discoveries show the damage the virus causes to males, at least in mice.

In mice and men

Mice are not by nature susceptible to Zika: the findings may not apply to humans. That said, the murine study, using a strain of the virus engineered to attack mice, shows serious damage to mouse testes, which may be small, but the problem is not.

About 80% of the mice involved in their model experienced extensive injury to their male tissue, Diamond told Haaretz.

Man wearing a homemade mosquito costume protests the lack of U.S. Congressional approval to fund a federal response to the Zika virus, on Capitol Hill, Washington. Sept. 15, 2016.
Jacquelyn Martin, AP

By three weeks after infection, the team saw up to about 80% reduction in murine testicle size, he clarified. "Zika injures the cells which are key for maintaining the architecture of the seminiferous tubules," Diamond explains. "We believe that damage to the cells and tissues ultimately results in loss of the ability to maintain the normal structure/size."

The mouse-adapted Zika also caused the male mice to suffer reduced levels of two sex hormones, testosterone and inhibin B, and sperm cells in the seminal fluid. Which in turn was found to contain zika particles.

"In the new study, we show that Zika virus infects spermatogonia and Sertoli cells in the testis," Diamond told Haaretz by email – those being stages in sperm cell development. "In the epididymis, we can see extensive amounts of viral RNA in the spermatocytes."

The Zika virus did more than just squat there: it caused damage to the semen-producing tubules and epididymis.

Viral presence in these areas was evident within seven days of infection. After 14 days, the virus was present at high levels throughout the reproductive system of most of the mice.

Preliminary fertility studies revealed reduced rates of pregnancy and viable fetuses from females mated with Zika-infected male mice compared to uninfected male mice, the scientists stated.

Whether an infected male's fertility will be affected in the long run remains to be seen. "Based on the extent and nature of damage, it is not likely to be reversible," Diamond hypothesizes.

The extent of the damage is clear. Its duration is not: "We detected high levels of viral RNA through day 42 (the latest we looked)," Diamond told Haaretz. "However, further studies beyond 42 days are needed."

So are studies on humans. Nobody's yet tested the concentration of zika in the reproductive system of infected men, though it has been known for months that the virus and viral RNA persist in human sperm and/or semen, Diamond says: "This is indeed why we did this study in the first place. To learn more about possible consequences of persistent infection in males."