Zika Virus Reduces Male Fertility in Mice

The Zika virus is known to influence developing fetuses and pregnant women, and now researchers are turning their attention to the possible effects on men. There is growing evidence that Zika can be sexually transmitted from an infected man to another partner, and studies show that the virus can remain in semen and sperm for months. Does the virus have long-term effects on the male reproductive tract and on male fertility?

Dr. Michael Diamond, professor of medicine, molecular microbiology, pathology and immunology at Washington University School of Medicine in St. Louis, and his team explored that question in mice. In a paper published in Nature, they report on how Zika affected the reproductive health of male mice, and the findings suggest more extensive damage to fertility than previously thought.

Diamond conducted extensive studies of the reproductive organs of male mice and found the virus damaged key sperm-making organs, as well as the stem cells that sire the sperm in a male. The testes in infected mice were also smaller compared to those in uninfected animals. Zika’s effect on male mice is two-fold, he says: first on the architecture, including the early sperm cells and the Sertoli cells in the testes, as well as the seminiferous tubules, which serve as the conveyer belt through which immature sperm cells pass as they receive the proper hormones to develop and mature. The virus also affects the sperm stem cells, which are the grandfather cells that produce all sperm. In essence, Zika hampers the sperm-making process by producing fewer sperm, as well as interfering with the development of the few sperm that do get released.

“In mice, the damage caused by Zika leads to not just loss of architecture but decreases in sperm count, loss of hormones and ultimately decreased fertility,” says Diamond. When the Zika-infected male mice mated, they were less likely to sire pups than uninfected males.

Whether similar damage is occurring in the testes of men infected with Zika isn’t clear yet. But the results do raise concern for the need to study men as well as women and babies infected with the virus. “These results suggest that if the same [effects] happen in men, we may need to be treating men much more aggressively than we probably thought,” he says. Up until now, the management of Zika in men focused mostly on preventing transmission of the virus. But it’s possible, says Diamond, that “if it turns out that Zika is causing more damage [to male reproduction], then we need to be more aggressive about treatment in men not just to interrupt sexual transmission but to prevent damage to their reproductive organs.”

Much more research is also needed to better understand how Zika affects male fertility. For one, related viruses like West Nile or dengue do not seem to cause the same damage to the testes in the mice that Diamond tested as Zika. His group is collaborating with researchers in South and Central America, where Zika is endemic, to start investigating how the infection affects male fertility. The scientists are planning to track things like sperm count, motility and testosterone levels to see if the changes they found in mice are also occurring in men.