Animal Reproduction (AR)
https://animal-reproduction.org/article/doi/10.1590/1984-3143-AR2023-0124
Animal Reproduction (AR)
ORIGINAL ARTICLE

Testicular damage without clinical manifestations in BALB/c mice experimentally infected with Zika virus

Derick Mendes Bandeira; Arthur da Costa Rasinhas; Raphael Leonardo; Marcos Alexandre Nunes da Silva; Eduarda Lima Araujo; Gisela Freitas Trindade; Renata Tourinho Santos; Ygara da Silva Mendes; Ortrud Monika Barth; Debora Ferreira Barreto-Vieira

Downloads: 1
Views: 57

Abstract

In 2015-2016, the Zika virus (ZIKV) caused a major epidemic in the Americas, increasing cases of microcephaly and Guillain-Barré syndrome. During this period, the discovery of ZIKV sexual transmission intensified studies on the impact of this virus on the reproductive organs. For this study, 2-month-old male BALB/c mice were infected with 1.26 x 106 PFU/mL of ZIKV in solution via the intravenous route. After three, seven, and fourteen days post-infection (DPI), blood and testicle samples were obtained to detect ZIKV RNA. The authors observed that the infected animals had slower weight gain than the control group. Viremia occurred only at 3DPI, and the ZIKV RNA was detected in one testis sample at 7DPI. The histopathological analysis of this organ revealed intense disorganization of the seminiferous tubules' structure, inflammatory infiltrate, necrosis, hemorrhage, fluid accumulation, congestion of blood vessels, and reduced sperm count. Ultrastructural analysis showed nuclear changes in tubule cells, activation of interstitial cells, and morphological changes in spermatozoa, in addition to fragmentation and decreased electron density of the genetic material of these cells. Thus, despite causing predominantly asymptomatic infections, ZIKV can cause significant subclinical and transient damage, including to male reproductive organs.

Keywords

Zika virus, Inbred BALB/c mice, testis

References

Araujo LM, Ferreira ML, Nascimento OJ. Guillain-Barré syndrome associated with the Zika virus outbreak in Brazil. Arq Neuropsiquiatr. 2016;74(3):253-5. http://doi.org/10.1590/0004-282X20160035. PMid:27050856.

Bandeira DM, Almeida ALT, Caldas GC, Barreto-Vieira DF. Modelos animais para infecção experimental pelo vírus Zika: uma revisão sistemática. REAS. 2023;23(5):e13209. http://doi.org/10.25248/reas.e13209.2023.

Barreto-Vieira DF, Schatzmayr OMB, Schatzmayr HG. Modelo Animal Experimental Para o Estudo da Patogênese dos Vírus Dengue Sorotipos 1 e 2: Manual de Técnicas. Rio de Janeiro: Editora Interciência; 2010.

Chan JF, Zhang AJ, Chan CC, Yip CC, Mak WW, Zhu H, Poon VK, Tee KM, Zhu Z, Cai JP, Tsang JO, Chik KK, Yin F, Chan KH, Kok KH, Jin DY, Au-Yeung RK, Yuen KY. Zika virus infection in dexamethasone-immunosuppressed mice demonstrating disseminated infection with multi-organ involvement including orchitis effectively treated by recombinant type I interferons. EBioMedicine. 2016;14:112-22. http://doi.org/10.1016/j.ebiom.2016.11.017. PMid:27884655.

Chiu CY, Sánchez-San Martín C, Bouquet J, Li T, Yagi S, Tamhankar M, Hodara VL, Parodi LM, Somasekar S, Yu G, Giavedoni LD, Tardif S, Patterson J. Experimental Zika virus inoculation in a New World monkey model reproduces key features of the human infection. Sci Rep. 2017;7(1):17126. http://doi.org/10.1038/s41598-017-17067-w. PMid:29215081.

Clancy CS, Van Wettere AJ, Morrey JD, Julander JG. Zika virus associated pathology and antigen presence in the testicle in the absence of sexual transmission during subacute to chronic infection in a mouse model. Sci Rep. 2019;9(1):1-0. http://doi.org/10.1038/s41598-019-44582-9. PMid:31171800.

D’Ortenzio E, Matheron S, de Lamballerie X, Hubert B, Piorkowski G, Maquart M, Descamps D, Damond F, Yazdanpanah Y, Leparc-Goffart I. Evidence of sexual transmission of Zika virus. N Engl J Med. 2016;374(22):2195-8. http://doi.org/10.1056/NEJMc1604449. PMid:27074370.

De La Vega MA, Piret J, Griffin BD, Rhéaume C, Venable MC, Carbonneau J, Couture C, das Neves Almeida R, Tremblay RR, Magalhães KG, Park YK, Roberts CC, Maslow JN, Sardesai NY, Kim JJ, Muthumani K, Weiner DB, Kobinger GP, Boivin G. Zika-induced male infertility in mice is potentially reversible and preventable by deoxyribonucleic acid immunization. J Infect Dis. 2019;219(3):365-74. http://doi.org/10.1093/infdis/jiy336. PMid:30053014.

Dick GW, Kitchen SF, Haddow AJ. Zika virus (I). Isolations and serological specificity. Trans R Soc Trop Med Hyg. 1952;46(5):509-20. http://doi.org/10.1016/0035-9203(52)90042-4. PMid:12995440.

Dowall SD, Graham VA, Rayner E, Hunter L, Atkinson B, Pearson G, Dennis M, Hewson R. Lineage-dependent differences in the disease progression of Zika virus infection in type-I interferon receptor knockout (A129) mice. PLoS Negl Trop Dis. 2017;11(7):e0005704. http://doi.org/10.1371/journal.pntd.0005704. PMid:28672028.

Hirsch AJ, Roberts VH, Grigsby PL, Haese N, Schabel MC, Wang X, Lo JO, Liu Z, Kroenke CD, Smith JL, Kelleher M, Broeckel R, Kreklywich CN, Parkins CJ, Denton M, Smith P, DeFilippis V, Messer W, Nelson JA, Hennebold JD, Grafe M, Colgin L, Lewis A, Ducore R, Swanson T, Legasse AW, Axthelm MK, MacAllister R, Moses AV, Morgan TK, Frias AE, Streblow DN. Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology. Nat Commun. 2018;9(1):263. http://doi.org/10.1038/s41467-017-02499-9. PMid:29343712.

Johnsen SG. Testicular biopsy score count–a method for registration of spermatogenesis in human testes: normal values and results in 335 hypogonadal males. Hormones. 1970;1(1):2-5. http://doi.org/10.1159/000178170. PMid:5527187.

Lanciotti RS, Kosoy OL, Laven JJ, Velez JO, Lambert AJ, Johnson AJ, Stanfield SM, Duffy MR. Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis. 2008;14(8):1232-9. http://doi.org/10.3201/eid1408.080287. PMid:18680646.

Mallet HP, Vial AL, Musso D. Bilan de l’epidemie a virus Zika en Polynesie Francaise, 2013–2014. Bulletin D’information Sanitaires, Épidémiologiques et Statistiques. 2015 May:20-1.

Martines RB, Bhatnagar J, de Oliveira Ramos AM, Davi HP, Iglezias SD, Kanamura CT, Keating MK, Hale G, Silva-Flannery L, Muehlenbachs A, Ritter J, Gary J, Rollin D, Goldsmith CS, Reagan-Steiner S, Ermias Y, Suzuki T, Luz KG, de Oliveira WK, Lanciotti R, Lambert A, Shieh WJ, Zaki SR. Pathology of congenital Zika syndrome in Brazil: a case series. Lancet. 2016;388(10047):898-904. http://doi.org/10.1016/S0140-6736(16)30883-2. PMid:27372395.

Miner JJ, Diamond MS. Zika virus pathogenesis and tissue tropism. Cell Host Microbe. 2017;21(2):134-42. http://doi.org/10.1016/j.chom.2017.01.004. PMid:28182948.

Muratori M, Tamburrino L, Marchiani S, Cambi M, Olivito B, Azzari C, Forti G, Baldi E. Investigation on the origin of sperm DNA fragmentation: role of apoptosis, immaturity and oxidative stress. Mol Med. 2015;21(1):109-22. http://doi.org/10.2119/molmed.2014.00158. PMid:25786204.

Peregrine J, Gurung S, Lindgren MC, Husain S, Zavy MT, Myers DA, Papin JF. Zika virus infection, reproductive organ targeting, and semen transmission in the male olive baboon. J Virol. 2019;94(1):e01434-19. http://doi.org/10.1128/JVI.01434-19. PMid:31597777.

Santa Rita TH, Barra RB, Peixoto GP, Mesquita PG, Barra GB. Association between suspected Zika virus disease during pregnancy and giving birth to a newborn with congenital microcephaly: a matched case–control study. BMC Res Notes. 2017;10(1):457. http://doi.org/10.1186/s13104-017-2796-1. PMid:28877754.

Schuler-Faccini L, Ribeiro EM, Feitosa IM, Horovitz DD, Cavalcanti DP, Pessoa A, Doriqui MJ, Neri JI, de Pina JM No, Wanderley HY, Cernach M. Possible association between Zika virus infection and microcephaly: Brazil, 2015. MMWR Morb Mortal Wkly Rep. 2016;65(3):59-62. http://doi.org/10.15585/mmwr.mm6503e2. PMid:26820244.

Sharma V, Sharma M, Dhull D, Sharma Y, Kaushik S, Kaushik S. Zika virus: an emerging challenge to public health worldwide. Can J Microbiol. 2020;66(2):87-98. http://doi.org/10.1139/cjm-2019-0331. PMid:31682478.

Wang HW, Li HH, Wu SC, Tang CK, Yu HY, Chang YC, Sung PS, Liu WL, Su MP, Yu GY, Huang LR, Chen CH, Hsieh SL. CLEC5A mediates Zika virus-induced testicular damage. J Biomed Sci. 2023;30(1):12. http://doi.org/10.1186/s12929-023-00906-6. PMid:36803804.

Wikan N, Smith DR. Zika virus: history of a newly emerging arbovirus. Lancet Infect Dis. 2016;16(7):e119-26. http://doi.org/10.1016/S1473-3099(16)30010-X. PMid:27282424.

Yu J, Liu X, Ke C, Wu Q, Lu W, Qin Z, He X, Liu Y, Deng J, Xu S, Li Y, Zhu L, Wan C, Zhang Q, Xiao W, Xie Q, Zhang B, Zhao W. Effective suckling C57BL/6, Kunming, and BALB/c mouse models with remarkable neurological manifestation for Zika virus infection. Viruses. 2017;9(7):165. http://doi.org/10.3390/v9070165. PMid:28661429.

Zhang NN, Zhang L, Deng YQ, Feng Y, Ma F, Wang Q, Ye Q, Han Y, Sun X, Zhang FC, Qi X, Wang G, Dai J, Xia X, Qin CF. Zika virus infection in Tupaia belangeri causes dermatological manifestations and confers protection against secondary infection. J Virol. 2019;93(8):e01982-18. http://doi.org/10.1128/JVI.01982-18. PMid:30728253.
 


Submitted date:
09/06/2023

6682b1b4a953952916325a42 animreprod Articles
Links & Downloads

Anim Reprod

Share this page
Page Sections