Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice
Wenqiang Ma1, Shihua Li2, Shuoqian Ma1
1State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing 100193, China.
Abstract:
Zika virus (ZIKV) persists in the semen of male patients, a first for flavivirus infection. Here, we demonstrate that ZIKV can induce inflammation in the testis and epididymidis, but not in the prostate or seminal vesicle, and can lead to damaged testes after 60 days post-infection in mice. ZIKV induces innate immune responses in Leydig, Sertoli, and epididymal epithelial cells, resulting in the production of pro-inflammatory cytokines/chemokines. However, ZIKV does not induce a rapid and abundant cytokine production in peritubular cell and spermatogonia, suggesting that these cells are vulnerable for ZIKV infection and could be the potential repositories for ZIKV. Our study demonstrates a correlation between ZIKV and testis infection/damage and suggests that ZIKV infection, under certain circumstances, can eventually lead to male infertility.
Insights
Zika virus (ZIKV) infects male mice testes, causing inflammation and damage. This flavivirus persistence in semen may lead to male infertility.
Area of Science:
- Virology
- Immunology
- Reproductive Biology
Background:
- Zika virus (ZIKV) is known to persist in human semen, a unique characteristic among flaviviruses.
- The impact of ZIKV on male reproductive organs and the potential for long-term consequences like infertility remain incompletely understood.
Purpose of the Study:
- To investigate the effects of ZIKV infection on the male reproductive system in a mouse model.
- To identify specific cell types within the testes and epididymis that are susceptible to ZIKV infection and contribute to the immune response.
Main Methods:
- Adult male mice were infected with ZIKV.
- Histopathological analysis of testes, epididymis, prostate, and seminal vesicles was performed at 60 days post-infection.
- Immunohistochemistry and cytokine/chemokine profiling were used to assess innate immune responses in different testicular cell types.
Main Results:
- ZIKV infection induced inflammation in the testes and epididymis, but not in the prostate or seminal vesicles.
- Significant testicular damage was observed 60 days post-infection.
- Leydig cells, Sertoli cells, and epididymal epithelial cells mounted an innate immune response with pro-inflammatory cytokine/chemokine production.
- Peritubular cells and spermatogonia showed limited cytokine production, suggesting they may serve as viral reservoirs.
Conclusions:
- ZIKV infection can cause significant inflammation and damage to the testes in mice.
- Specific testicular cell populations are vulnerable to ZIKV, potentially serving as viral reservoirs.
- These findings suggest a correlation between ZIKV infection and male reproductive damage, potentially leading to infertility.
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