Zika virus destroys testicles in mice

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As Zika infection lingers in male mice, the internal structure of the testes breaks down. In an uninfected mouse on the left, the cells in the testicle appear healthy, while in an infected mouse on the right, the internal structure of the testicle has collapsed and few developing sperm (pink) are present.
Credit: Prabagaran Esakky

Zika virus infection causes testicular shrinking, lower testosterone and fewer sperm in mice.

Jennifer Govero and Prabagaran Esakky and colleagues from Washington University infected male mice with two strains of the Zika virus and found the rodents ended up with lower hormone levels and testicle tissue loss after just two weeks.

Writing in Nature, the researchers stress how these observations translate to humans is unclear, but long-term studies of sperm viability in men are warranted.

Much research into the Zika virus, a strain of which most recently reared its head in Brazil in October, has been into the effects on pregnant women and foetuses.

Mouse studies this year showed the virus also works its way into testes tissue. But no one had tracked the virus’ long-term effects on sperm, hormones and offspring.

Govero, Esakky and their crew infected groups of mice with the Zika virus – one strain from Africa and another from Asia – and dengue fever.

After seven days, the African Zika virus had made its way into mouse testes and epididymis, a tube that carries and stores sperm.

After another week, high levels of the virus was found throughout the reproductive organs of most mice, including the mature sperm.

By this time, there was a noticeable decrease in testis size and weight, with most of the infected mouse testicles around half the weight of those of healthy counterparts. In particular, the seminiferous epithelium, where sperm developed, was almost completely destroyed.

After another week – at 21 days – Zika-infected testes in all but one mouse had shrunk to less than a fifth of the uninfected mouse testes. Damage to the reproductive architecture continued.

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The testicles of male mice showed cellular damage and shrinkage three weeks after Zika infection. On the left is a healthy mouse testicle; on the right, a testicle following Zika infection.
Credit: Prabagaran Esakky

This deterioration appeared to be partly inflicted by the Zika virus particles and partly by the body’s immune response. Inflammatory cells, infiltrating the injured areas, exacerbated the damage.

While testosterone levels were raised at day seven after infection – perhaps because the inflammatory environment kicked the hormone-producing cells into higher gear – levels dropped markedly at day 14 and stayed low.

Female mice, mating with infected males, had fewer pregnancies with fewer healthy young compared to non-infected males.

The Asian strain also inflicted damage, but not to the same extent as the African. And dengue didn’t make it into the testes at all.

But it’s worthwhile to note two massive caveats to this study.

The first, which the authors freely acknowledge, is all their subjects were mice, and mouse models of disease aren’t perfect approximations for humans. How a disease courses through us could be very different to its actions on a mouse’s body.

And the second is while the African strain was more pathogenic in mice than the Asian, so wreaked more damage, we don’t know what the Brazilian strain would do – the one currently making the rounds in the Americas.

Still, the researchers write, “genitourinary signs and symptoms in [Zika virus]-infected humans have been reported” such as blood in semen and painful urination and monitoring the reproductive health of infected men in the long-term is needed.

“If testosterone levels drop in men like they did in the mice, I think we’ll start to see men coming forward saying, ‘I don’t feel like myself,’ and we’ll find out about it that way,” Kelle Moley, co-author of the said.

“You might also ask, ‘Wouldn’t a man notice if his testicles shrank?’ Well, probably. But we don’t really know how the severity in men might compare with the severity in mice. I assume that something is happening to the testes of men, but whether it’s as dramatic as in the mice is hard to say.”

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