Research finds effects of Zika virus on male reproductive system in mice

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.

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.

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.

Citation: Zika virus infection damages the testes in mice. Authors: Jennifer Govero, Prabagaran Esakky, Suzanne M. Scheaffer, Estefania Fernandez, Andrea Drury, Derek J. Platt, Matthew J. Gorman, Justin M. Richner, Elizabeth A. Caine, Vanessa Salazar, Kelle H. Moley & Michael S. Diamond
DOI: http://dx.doi.org/10.1038/nature20556
Journal: Nature
Research Funding: NIH/National Institute of Allergy and Infectious Diseases
Adapted from press release by Washington University in St Louis