Could Zika Virus Have Lasting Impact on Male Fertility?

Posted on November 8th, 2016 by Dr. Francis Collins

Recent research has shown that the mosquito-borne Zika virus has the potential to cause serious health problems, including severe birth defects in humans. But the damaging effects of Zika might not end there: results of a new mouse study show that the virus may also have an unexpected negative—and possibly long-lasting—impact on male fertility.

In work published in the journal Nature, an NIH-funded research team found that Zika infections can persist for many weeks in the reproductive systems of male mice [1]. As a result of this infection, levels of testosterone and other sex hormones drop, sperm counts fall, and, in some animals, the testicles shrink to 1/10th of their normal size, possibly irreversibly. All of this adds up to Zika-infected male mice that are significantly less fertile than their healthy counterparts—producing about a quarter as many viable offspring as normal when mated with female mice. While mice are certainly not humans, the results underscore the urgent need for additional research to examine the full spectrum of Zika’s health effects in men, women, and children of both sexes.

There are a few things that are already known about Zika virus and men. One is that the virus can be sexually transmitted. Another is Zika has been detected in the semen of men months after they were infected.

The latter finding recently became even more disturbing when a mouse study, led by Michael Diamond of the Washington University School of Medicine, St. Louis, found Zika infections spread rapidly to the reproductive systems of adult male mice and turned out to have long term consequences [2].

To look for long term health effects, the team infected male mice in the lab with two strains of Zika virus, one from the Pacific nation of French Polynesia and the other from the African nation of Senegal. For comparison, the researchers infected another group of male mice with a different virus: the mosquito-borne dengue virus.

The researchers detected Zika virus in the testicles and other parts of the male reproductive system within a week of infection with either of the two strains. Evidence of the Zika virus turned up in mature sperm cells and also three cell types (spermatogonia, primary spermatocytes, and Sertoli cells) involved in sperm production. In contrast, male mice infected with dengue virus showed no evidence of infection in their reproductive systems.

A week after infection with Zika, the testicles of the mice still looked normal. But by week two, they showed a noticeable decrease in size as infected cells in the reproductive tissues died. By week three, the internal tissue structure of the animals’ testicles was essentially destroyed.

While the mice cleared the virus several weeks later, the damage to spermatogenesis was done. Diamond says he and his colleagues doubt that the mice could ever fully recover from that level of injury. However, additional long-term studies will be needed to confirm the long-term effects.

Not surprisingly, the physical damage to the animals’ reproductive systems also compromised their ability to produce two important sex hormones, including testosterone and inhibin B, both of which are important in sperm production. This made their sperm counts plummet and greatly reduced their fertility. When the researchers mated their Zika-infected male mice with healthy females, only about 20 percent became pregnant. That’s compared to an 80 percent success rate in pairings of healthy males and females.

Plenty of questions remain, most especially whether the findings in mice will hold true in people. One question that must be asked is whether the viral dose delivered to the mice is similar to what a human male would experience after being bitten by a Zika-infected mosquito. Diamond and his colleagues are now beginning to examine whether men who have been infected show evidence of similar damage and, if so, to what extent. They also hope to better understand why Zika specifically targets cells of the male reproductive system and whether the immune system contributes to causing the tissue damage.

If Zika turns out to affect male fertility in humans, the good news is that animal studies can speed the search for potential treatments. In fact, Diamond and his colleagues have already begun experiments in their male mice to test whether treatment with highly neutralizing antibodies could help to fend off Zika before tissue damage and infertility occurs.

References:

[1] Zika virus infection damages the testes in mice. Govero J, Esakky P, Scheaffer SM, Fernandez E, Drury A, Platt DJ, Gorman MJ, Richner JM, Caine EA, Salazar V, Moley KH, Diamond MS. Nature. 2016 Oct 31. [Epub ahead of print]

[2] A Mouse Model of Zika Virus Pathogenesis. Lazear HM, Govero J, Smith AM, Platt DJ, Fernandez E, Miner JJ, Diamond MS. Cell Host Microbe. 2016 May 11;19(5):720-730.

Links:

Zika Virus (National Institute for Allergy and Infectious Diseases/NIH)

Zika and Sexual Transmission (Centers for Disease Control and Prevention)

Michael Diamond (Washington University School of Medicine, St. Louis)

NIH Support: National Institute for Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Center for Advancing Translational Sciences; National Institute of General Medical Sciences