Potential effect of Zika virus infection on human male fertility?

Avelino‐Silva, Vivian Iida; Alvarenga, Conrado; Abreu, Ana Carolina; Tozetto‐Mendoza, Tânia Regina; Canto, Cynthia L.M.; Manuli, Erika R.; Mendes‐Correa, Maria Cássia; Sabino, Éster Cerdeira; Figueiredo, Walter Manso; Segurado, Aluísio Cotrim; Mayaud, Philippe

doi:10.1590/s1678-9946201860064

Cited by 23 publications

(12 citation statements)

References 13 publications

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“…In addition, infection with ZIKV leads to impaired human spermatozoa production demonstrated by decreased sperm count in the early stage of ZIKV infection (Joguet et al, 2017). And even 1 year after ZIKV infection, abnormal spermogram results could still be observed (Avelino-Silva et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Montelukast, an Anti-asthmatic Drug, Inhibits Zika Virus Infection by Disrupting Viral Integrity

Chen

Wang

et al. 2020

Front. Microbiol.

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The association of Zika virus (ZIKV) infection and severe complications including neurological sequelae especially fetal microcephaly has aroused global attentions since its outbreak in 2015. Currently, there are no vaccines or therapeutic drugs clinically approved for treatments of ZIKV infection, however. And the drugs used for treating ZIKV in pregnant women require a higher safety profile. Here, we identified an anti-asthmatic drug, montelukast, which is of safety profile for pregnant women and exhibited antiviral efficacy against ZIKV infection in vitro and in vivo. And we showed that montelukast could disrupt the integrity of the virions to release the viral genomic RNA, hence irreversibly inhibiting viral infectivity. In consideration of the neuro-protective activity that montelukast possessed, which was previously reported, it is promising that montelukast could be used for patients with ZIKV infection, particularly for pregnant women.

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Section: Introductionmentioning

confidence: 99%

Montelukast, an Anti-asthmatic Drug, Inhibits Zika Virus Infection by Disrupting Viral Integrity

Chen

Wang

et al. 2020

Front. Microbiol.

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“…This carrier status in males may make men more likely to sexually transmit ZIKV to females than vice versa [1]. Whether or not male ZIKV infection negatively affects male fertility has yet to be answered [31,32]. Only immunodeficient mice have been developed as models of male ZIKV infection; however, because of the confounding immune status of these animals, this model does not recapitulate infection in men.…”

mentioning

confidence: 99%

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Schwarz

Oliveira

Bonfante

et al. 2020

Viruses

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Zika virus (ZIKV) is an arbovirus that causes birth defects, persistent male infection, and sexual transmission in humans. The purpose of this study was to continue the development of an ovine ZIKV infection model; thus, two experiments were undertaken. In the first experiment, we built on previous pregnant sheep experiments by developing a mid-gestation model of ZIKV infection. Four pregnant sheep were challenged with ZIKV at 57-64 days gestation; two animals served as controls. After 13-15 days (corresponding with 70-79 days of gestation), one control and two infected animals were euthanized; the remaining animals were euthanized at 20-22 days post-infection (corresponding with 77-86 days of gestation). In the second experiment, six sexually mature, intact, male sheep were challenged with ZIKV and two animals served as controls. Infected animals were serially euthanized on days 2-6 and day 9 post-infection with the goal of isolating ZIKV from the male reproductive tract. In the mid-gestation study, virus was detected in maternal placenta and spleen, and in fetal organs, including the brains, spleens/liver, and umbilicus of infected fetuses. Fetuses from infected animals had visibly misshapen heads and morphometrics revealed significantly smaller head sizes in infected fetuses when compared to controls. Placental pathology was evident in infected dams. In the male experiment, ZIKV was detected in the spleen, liver, testes/epididymides, and accessory sex glands of infected animals. Results from both experiments indicate that mid-gestation ewes can be infected with ZIKV with subsequent disruption of fetal development and that intact male sheep are susceptible to ZIKV infection and viral dissemination and replication occurs in highly vascular tissues (including those of the male reproductive tract).Viruses 2020, 12, 291 2 of 23 and negative gestational outcomes when infection occurs during pregnancy. In humans, ZIKV is believed to result in trimester-specific effects to the fetus [2][3][4][5][6][7]. Established animal models of ZIKV infection during pregnancy that result in vertical transmission include non-human primates (NHP) and type-1 interferon/interferon receptor deficient mice. In NHP models, first trimester infection most frequently results in fetal demise and reduced fetal development even in asymptomatic mothers, while second trimester infections tend to produce fetuses with higher viral loads but greater fetal viability [8][9][10]. In all NHP models, fetal pathology ranges from mild to severe manifestations, consistent with Congenital Zika Syndrome (CZS) seen in humans [11][12][13][14][15][16]. While NHP models of ZIKV infection during pregnancy recapitulate human infection, other outbred host models can serve as surrogates when ethical and economic constraints create obstacles to the use of NHP.Sheep offer a unique animal model for translational biomedical research, and have long been used as a model for human pregnancy and fetal development due to longer gestation and comparably staged rates of fetal d...

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“…Results also reflected an early increase of follicle-stimulating hormone and inhibin B, which recovered over time. By contrast, in a cross-sectional study after the 2016 epidemic in Brazil, Avelino-Silva et al 38 examined serum hormones and semen samples in 6 patients 1 year after symptoms. In all patients, serum hormones were normal, and semen RT-PCR RNA was negative, but impaired motility was seen in all 3 samples tested and low count was noted in 1 of 5 patients.…”

Section: Methodsmentioning

confidence: 96%

Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men

Payne

Kenny

Scovell

et al. 2020

Sexual Medicine Reviews

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Introduction The 21st century has seen a series of viral pandemics that have collectively infected millions of individuals. To understand factors that may contribute to viral spread and address long-term health sequelae for survivors, it is important to review evidence regarding viral presence in semen, sexual transmission potential, and possible effects on fertility. Aim To review the current literature regarding the sexual transmissibility of recent viral pandemics and their effects on semen parameters and fertility. We review evidence for the following viruses: Ebola, Zika, West Nile, pandemic influenza, severe acute respiratory syndrome (SARS), and SARS-corona virus-2 (SARS-CoV-2). Methods A literature search was conducted to identify relevant studies. Titles and abstracts were reviewed for relevance. References from identified articles were searched and included, if appropriate. Main Outcome Measures The main outcome measure of this study was reviewing of peer-reviewed literature. Results Both the Ebola virus and Zika virus are present in semen, but only the Zika virus shows consistent evidence of sexual transmission. Current evidence does not support the presence of the West Nile virus, pandemic influenza, SARS, and SARS-CoV-2 in semen. The Zika virus appears to alter semen parameters in a way that diminishes fertility, but the effect is likely time limited. The West Nile virus and SARS have been associated with orchitis in a small number of case reports. Viruses that cause febrile illness, such as pandemic influenza, SARS, and SARS-CoV-2, are associated with decreased sperm count and motility and abnormal morphology. SARS and SARS-CoV-2 may interact with angiotensin-converting enzyme 2 receptors present in the testes, which could impact spermatogenesis. Conclusions We have reported the presence in semen, sexual transmission potential, and fertility side effects of recent viral pandemics. Overall, semen studies and fertility effects are highly understudied in viral pandemics, and rigorous study on these topics should be undertaken as novel pandemics emerge. Payne K, Kenny P, Scovell JM, et al. Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications for Men. Sex Med Rev 2020;XX:XXX–XXX.

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Potential effect of Zika virus infection on human male fertility?

Cited by 23 publications

References 13 publications

Montelukast, an Anti-asthmatic Drug, Inhibits Zika Virus Infection by Disrupting Viral Integrity

Montelukast, an Anti-asthmatic Drug, Inhibits Zika Virus Infection by Disrupting Viral Integrity

Experimental Infection of Mid-Gestation Pregnant Female and Intact Male Sheep with Zika Virus

Twenty-First Century Viral Pandemics: A Literature Review of Sexual Transmission and Fertility Implications in Men

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