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Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation

Authors :
Wei Yang
Li-Bo Liu
Feng-Liang Liu
Yan-Hua Wu
Zi-Da Zhen
Dong-Ying Fan
Zi-Yang Sheng
Zheng-Ran Song
Jia-Tong Chang
Yong-Tang Zheng
Jing An
Pei-Gang Wang
Source :
Nature Communications. 14
Publication Year :
2023
Publisher :
Springer Science and Business Media LLC, 2023.

Abstract

Zika virus (ZIKV) is a potential threat to male reproductive health but the mechanisms underlying its influence on testes during ZIKV infection remain obscure. To address this question, we perform single-cell RNA sequencing using testes from ZIKV-infected mice. The results reveal the fragility of spermatogenic cells, especially spermatogonia, to ZIKV infection and show that the genes of the complement system are significantly upregulated mainly in infiltrated S100A4 + monocytes/macrophages. Complement activation and its contribution to testicular damage are validated by ELISA, RT‒qPCR and IFA and further verify in ZIKV-infected northern pigtailed macaques by RNA genome sequencing and IFA, suggesting that this might be the common response to ZIKV infection in primates. On this basis, we test the complement inhibitor C1INH and S100A4 inhibitors sulindac and niclosamide for their effects on testis protection. C1INH alleviates the pathological change in the testis but deteriorates ZIKV infection in general. In contrast, niclosamide effectively reduces S100A4 + monocyte/macrophage infiltration, inhibits complement activation, alleviates testicular damage, and rescues the fertility of male mice from ZIKV infection. This discovery therefore encourages male reproductive health protection during the next ZIKV epidemic.

Details

ISSN :
20411723
Volume :
14
Database :
OpenAIRE
Journal :
Nature Communications
Accession number :
edsair.doi...........adced47f9c3a5b8e2add0c2199a2fae7
Full Text :
https://doi.org/10.1038/s41467-023-38223-z