Abstract
Zika virus (ZIKV) has been reported by several groups as an important virus causing pathological damage in the male reproductive tract. ZIKV can infect and persist in testicular somatic and germ cells, as well as spermatozoa, leading to cell death and testicular atrophy. ZIKV has also been detected in semen samples from ZIKV-infected patients. This has huge implications for human reproduction. Global scientific efforts are being applied to understand the mechanisms related to arboviruses persistency, pathogenesis, and host cellular response to suggest a potential target to develop robust antiviral therapeutics and vaccines. Here, we discuss the cellular modulation of the immunologic and physiologic properties of the male reproductive tract environment caused by arboviruses infection, focusing on ZIKV. We also present an overview of the current vaccine effects and therapeutic targets against ZIKV infection that may impact the testis and male fertility.
Highlights
The testis is a reproductive gland that is part of the internal structures of the male reproductive tract (MRT) and is involved in spermatogenesis and steroidogenesis
The integrity and infectivity of the viral particles were accessed and confirmed in the report. This strongly suggests that this virus can be sexually transmitted once it is capable of maintaining infective parameters, no data are available confirming the capability of Yellow Fever virus (YFV) persistence and impact in the MRT, or sexual transmission associated with the infection
DNA-based vaccination and/or live attenuated Zika virus (ZIKV) vaccines showed high efficacy against MRT damage induced by ZIKV and are a very prominent therapeutic tool to prevent male infertility caused by ZIKV
Summary
The testis is a reproductive gland that is part of the internal structures of the male reproductive tract (MRT) and is involved in spermatogenesis and steroidogenesis. Of pro-inflammatory cytokines, such as interleukin-1β and tumoral necrosis factor-α, and present a higher expression of nitric oxide synthase (iNOS), demonstrating a pro-inflammatory profile, a key characteristic of type 1 macrophage (M1) [32] The communication of these cells with LCs, SCs, and germ cells seems to be important in the development process that leads to sperm production. It was reported that the production of intense pro-inflammatory cytokines is related to loss of BTB integrity and loss of viable sperm, leading to infertility [30,41] Avoiding this massive activation, the testis presents a unique tolerogenic microenvironment, making the organ immune-privileged, and protecting mature gametes against the immune-cell-induced death and inflammation. Many pathogens have been shown to cause male infertility by many mechanisms, induced inflammation being the key for most of them
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