Yale School of Medicine researchers have linked Zika virus to testicular dystrophy in mice, a discovery with potential consequences for the management of the virus in humans.

Zika virus is primarily transmitted through the bite of the Aedes mosquito, though it can also be transmitted through sexual intercourse and from a pregnant woman to her fetus. The virus gained international attention during a widespread outbreak in 2016, causing the World Health Organization to declare a public health emergency of international concern.

The researchers studied Dengue virus for a number of years before shifting to Zika after the outbreak, according to Andrew Hastings, a postdoctoral fellow at the Yale School of Medicine and a co-author of the study. He said the lab has been working on developing a mouse model for the virus, to help scientists develop a potential vaccine or treatment.

In order to do this, researchers inject mice with Zika and observe the effects of the virus on various organs. These mice lack components of their immune system, so they are especially susceptible to the virus, Yockey said.

One result was found in the reproductive organs of male mice 21 days post-infection. The testes of the Zika-infected mice were notably smaller than those of the non-infected control group, said Ryuta Uraki, a postdoctoral fellow at the Yale School of Medicine and the lead author of the study.

“These results may be very relevant for human men who have been infected with Zika virus, especially those trying to have children,” Yockey said. “They might have fertility problems later in life due to low sperm count.”

With Zika virus still an issue of international concern, labs across the world have been conducting similar research, reaching similar conclusions, Hastings said.

Previous research on human subjects has shown that the virus persists in semen after the symptomatic phase of the virus has passed, said Laura Yockey GRD ’19, co-author of the study.

So far, the consensus among these papers is that Zika reproduction in the tubules where sperm production takes place negatively affects fertility, Uraki said. He added, however, that this paper is the only one to study the presence of Zika in the interstitial tissue of the testes, where testosterone is produced.

“Our paper shows that the virus is able to replicate in the testes of the mouse,” Hastings said. “And that reproduction is what leads to smaller testes and lower testosterone production.”

Identifying causation presented the researchers with a challenge. On one hand, the virus may affect testosterone-producing cells, which leads to lower testosterone production, causing shrinkage of the testes. On the other hand, the virus may kill other cells in the testes, affecting the testosterone-producing cells and lowering testosterone production, Hastings said. The direction of causation remains to be discovered by future research.

It has been widely reported that Zika virus can affect the reproductive system of human females, and that the virus is sexually transmittable even after it is not detectable in most parts of the body, Uraki said. However, there is less information regarding the effects of the virus on the reproductive organs of human males.

“Now that we have looked at the effects of [Zika] in immune deficient mice, it is important that we study the effect of Zika virus on testicular atrophy in humans,” Uraki said.

Zika virus was first identified in monkeys in Uganda in 1947 by researchers studying yellow fever.