Zika Virus Infections Lead to Male Infertility in Mice

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A joint study carried out by teams from China Agricultural University and the Institute of Microbiology of Chinese Academy of Sciences and lead by Prof Li Xiangdong and Prof George Gao Fu respectively, have shown that Zika virus can cross the blood-testes-barrier under certain conditions such as immunodeficiency, and infect the reproductive tract in male mice.

In humans, Zika virus infections have been associated with microcephaly in newborns and Guillain-Barré Syndrome. The recent study findings, published online in the journal Cell and entitled “Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice” provide new insights into the pathogenic mechanisms of Zika virus disease.

Their study has revealed how infection with Zika virus infection in mice can lead to acute and chronic testicular damage, eventually leading to infertility. Acute inflammation of the testes was observed eight days post-infection(Acute orchitis/epididymis) along with decreased levels of testosterone, with symptoms persisting 16 days after infection.

At 30 days after infection, a breakdown in the morphology of the testes and disruption of the seminal vesicles can be observed, resulting in completely atrophied testes and seminal vesicles by 60 days after infection.

Further studies show that Zika virus can infect the testes and epididymis, but not the prostates or seminal vesicles in the male reproductive tract. Specifically, Sertoli, Leydig, and epididymal epithelia cells secrete large quantities of cytokines/chemokines after Zika virus infection, which may have contributed to the observed damage in the testes/epididymis. In contrast, peritubular cells and spermatogonia did not secrete cytokines/chemokines after Zika virus infection, suggesting that these cells may harbour Zika virus, allowing the virus to persist in the male genital tract.

Zika virus is closely related to Dengue virus, Japanese encephalitis virus, and West Nile virus, all of which are transmitted primarily via mosquito bites. However, the observation that Zika virus can also persist in the semen of convalescent male patients suggest that this pathogen can also be sexually transmitted. This study supports this hypothesis, and highlights the fact that more studies are needed in order to completely understand all mechanisms of Zika virus pathogenesis.

Figure: Zika virus infection damages testis and potentially results in male infertility in mice. (Image by Professor George Fu Gao's group)
Figure: Zika virus infection damages testes and potentially results in male infertility in mice. (Image by Professor George Fu Gao’s group)