Zika shrinks testicles in mice, study finds

Zika virus not only hangs around in testicles for months after it disappears from the bloodstream, it also shrinks them, new research has found.

The fact that the virus can persist in the reproductive system long after its acute phase has passed has been known since 2015, when it was found in the semen of a man who had been infected during an outbreak in French Polynesia.

To better understand the mechanisms involved, a team led Ryuta Uraki and Jesse Hwang from Yale University’s School of Medicine injected mice with a non-lethal strain of the disease. Their study is published in Science Advances.

The mice all became ill five days after being infected. After nine days, the virus was found to be fast disappearing from the bloodstream, and by 21 it was undetectable. However, in what the researchers termed an unexpected outcome, by 21 days after being infected the mice had testicles “significantly smaller” than healthy controls, and were experiencing “progressive testicular atrophy”.

Further investigation revealed that Zika antigens were present in the testes’ Leydig cells – a type that supports sperm production by generating testosterone. There was also an “overwhelming amount” of antigen in the epididymal duct, an area associated with sperm storage.

The findings suggest that the infected Leydig cells were unable to produce normal amounts of testosterone, leading to organ shrinkage. Indeed, at 21 days some of the mice had testosterone levels so low that they were undetectable by conventional assay.

Simultaneously, the concentration of the virus in the epididymal duct suggests a clear mechanism for male-to-female sexual transmission.

Uraki, Hwang and colleagues suggest that the atrophied testes may also indicate a loss of fertility, and speculate that a similar effect might be found in infected humans.

If so, it represents another unpleasant aspect to this emerging tropical disease, which has now been shown to be transmitted not only by mosquitos, but also between mothers and children, and between sexual partners.

The linkage of Zika with testicular atrophy, say the researchers, underlines “an urgent need to develop vaccines and antiviral therapeutics”.