Abstract
Objective: To investigate the impact of direct Zika virus infection on male fertility and the body development of mouse offspring. Methods: Adult BALB/C mice were divided into three experimental groups: placebo, immunosuppressed, and immunosuppressed/infected. Immunosuppressed males received dexamethasone (50 mg/kg), and the infected group was inoculated with 200 µl (1x10⁴) of ZIKV. After 35 days, the males were mated. Fertility assessments included the number of pregnant females, fetal viability, losses, and biometric measurements. Fetal body morphometry and analysis of skeletal ossification centers were also performed. Results: The infected group exhibited an 85% reduction in the ossification centers of the sternum. No significant differences were observed in other somatic, fertility, or placental parameters. Infection was confirmed by RT-PCR. Conclusion: Non-viable spermatozoa may be numerically insignificant or potentially reabsorbed by the epididymis, as no changes in fertility were observed. In terms of offspring development, the ZIKV-infected group exhibited skeletal alterations, suggesting a possible delay in locomotor system development.
References
BROGUEIRA P, MIRANDA AC. Vírus Zika: Emergência de um Velho Conhecido Zika Virus. Revista de Sociedade Portuguesa de Medicina Interna, 2017.
BUSNELLI A, et al. Sperm DNA fragmentation and idiopathic recurrent pregnancy loss: results from a multicenter case–control study. Andrology, 2023; 11(8).
CAETANO CCS, et al. Mechanistic insights into bone remodelling dysregulation by human viral pathogens.
Nature Microbiology, 2024; 9: 322–335.
CALVET GA, et al. Study on the persistence of Zika virus (ZIKV) in body fluids of patients with ZIKV infection in Brazil. BMC infectious diseases, 2018; 18.
CHAN, JFW, et al. 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 – 122.
DIAS FCR, et al. How bad is brazilian ginseng extract for reproductive parameters in mice? Histol Histopathol, 2020; 35(10).
DIAS FCR, et al. Pfaffia glomerata polyploid accession compromises male fertility and fetal development. J Ethnopharmacol, 2023; 314.
DIMASUAY KG, et al. Placental Responses to Changes in the Maternal Environment Determine Fetal Growth. Front Physiol, 2016; 7(12).
DOMINGO, E. Mechanisms of viral mutation. Cell and Molecular Life Sciences, 2016; 73(23): 4433–4448.
DUARTE G, et al. Zika virus infection in pregnant womanand microcephaly. Rev. Bras. Ginecol.Obst. 2017; 39(5).
FAISAL K, AKBARSHA MA. Control of sperm quality in the epididymis by disintegration and removal–A transmission electron microscopy study of abnormal sperm of aflatoxin-treated rat. Journal of Reproductive Healthcare and Medicine, 2024; 5(4).
GOVERO J, et al. Zika virus infection damages the testes in mice. Nature, 2016; 540: 438–442.
GUO Y, et al. Correlation between viral infections in male semen and infertility: a literature review. Virology Journal, 2024; 21(167).
Herring SW. Musculoskeletal system development. In: Knobil and Neill's Physiology of Reproduction. 2008
HEBLING MN, et al. Zika virus infection in BALB/c mice causes transient subclinical testicular damage. Animal Reproduction, 2024; 21(1): e20230124.
HIRASAWA T, KURATANI S. Evolution and development of the vertebrate sternum. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, 2015; 324(4): 287-297.
International Comitee on Taxonomy of Viruses. Disponível em: https://ictv.global/. Acesso em: 28 de maio de 2025.
LAPORTA GZ, et al. Global Distribution of Aedes aegypti and Aedes albopictus in a Climate Change Scenario of Regional Rivalry. Insects, 2023; 14(49).
LI G. et al. Characterization of cytopathic factors through genome-wide analysis of the Zika viral proteins in fission yeast. Proc Natl Acad Sci, 2017; 114.
MA W, et al. Zika Virus Causes Testis Damage and Leads to Male Infertility in Mice. Cell, 2017; 168: 542.
MCLEOD MJ. Differential staining of cartilage and bone in whole mouse fetuses by alcian blue and alizarin red S. Teratology, 1980 Dec;22(3):299-301.
MENDES, CF. Efeito do extrato de Mikania glomerata Sprengel (Guaco) sobre a implantação e o desenvolvimento embrionário e placentário em camundongos. Dissertação (Mestrado em Biologia Celular e Tecidual). Instituto de Ciências Biomédicas, Universidade de São Paulo, 2012.
MUMTAZ N. et al. Zika virus infects human osteoclasts and blocks differentiation and bone resorption.
Emerging Microbes & Infections, 2022; 11(1): 1621–1634.
OLIVEIRA TRDP, et al. Consequences of the modulation of gestational resistance training intensity for placental cell composition and nutrient transporter expression. Placenta, 2025.
ORGANIZAÇÃO MUNDIAL DA SAÚDE (OMS). Manual para análise e processamento de sêmen humano. 6. ed. Genebra: OMS, 2021.
ORTEGA N, et al. Osteoblast-specific overexpression of TGF-β1 blocks bone formation and causes osteopenia by a non-cell-autonomous mechanism. Developmental Cell, 2004; 6(1): 109–120.
RAY P, et al. Transcriptional signatures throughout development: the effects of mouse embryo manipulation in vitro. Reproduction, 2017; 153(1): 107–118.
RUGG-GUNN PJ, et al. Early human development and stem cell-based human embryo models. Development, Cambridge, 2023; (150): 201797.
SANTOS J, MENESES BM. An integrated approach for the assessment of the Aedes aegypti and Aedes albopictus global spatial distribution, and determination of the zones susceptible to the development of Zika virus. Acta Trop, 2017; 168.
SILVA AA. A infecção pelo vírus Zika causa alterações morfológicas testiculares e espermáticas em camundongos balb/c adultos. Dissertação (Mestrado em Biologia Aplicada à Saúde) - Instituto Keizo Asami. Universidade Federal de Pernambuco, Recife, 2020.
SHENG ZY, et al. Sertoli cells are susceptible to ZIKV infection in mouse testis. Frontiers in Cellular and Infection Microbiology, 2017; 7.
STORONI S, et al. Pathophysiology of respiratory failure in patients with osteogenesis imperfecta: a systematic review. Annals of Medicine, 2021; 53(1): 1676–1687.
URAKI R, et al. Zika virus causes testicular atrophy. Sci. Adv, 2017; (3).
VERNET P, et al. Antioxidant strategies in the epididymis. Mol Cell Endocrinology, 2004; 216.
WAI-SUN O, et al. Male genital tract antioxidant enzymes-Their ability to preserve sperm DNA integrity. Molecular and Cellular Endocrinology, 2006; 250(2).
WATANABE S, VASUDEVAN SG. Clinical and experimental evidence for transplacental vertical transmission of flaviviruses. Antiviral research, 2023; 210.
Wu KY, et al. Vertical transmission of Zika virus targeting the radial glial cells affects cortex development of offspring mice. Cell research, 2016; 26(6): 645-654.
YEKELER E, et al. Pseudomass of the sternal manubrium in osteogenesis imperfecta.
Skeletal Radiology, 2003; 32(6): 371–373.
ZHANG Y, et al. Zika Virus Infection in the Ovary Induces a Continuously Elevated Progesterone Level and Compromises Conception in Interferon Alpha/Beta Receptor-Deficient Mice. J Virol., 2022; 96: e01189-21.
ZHOU W, et al. Mean number of DNA breakpoints: Illuminating sperm DNA integrity and in vitro fertilization outcomes. Fertility and Sterility, 2024; 121(2): 264-270.
