Abstract
It is known that cadmium induces damage to the testis. However, the significant cadmium impact on the testicular architecture and the mechanisms involved in this process are not clear. Besides, the relationship between dose, route, and time of exposure and injuries remains poorly understood. Thus, we aimed to assess whether cadmium exposure in any dose, route, and time of exposure causes significant alteration in the testicular tissue of murine models, as well as the main mechanisms involved. We performed a structured search on the Medline/PubMed and Scopus databases to retrieve studies published until September 2018. The results were organized into an Adverse Outcome Pathway (AOP) framework. Also, a bias analysis of included studies was performed. We included 37 studies, and most of them identified significant histopathologies in both tubule and intertubule regarding routes, in a dose- and time-dependent manner. The damages were observed after the first hours of exposure, mainly vascular damages suggesting that vasculature failure is the primary mechanism. The AOP showed that potential molecular initiating events may mimic and interfere with essential elements disrupting proteins (structural and antioxidants), change in the oxidative phosphorylation enzyme activities, and gene expression alteration, which lead to reproductive failure (adverse outcome). Analysis of methodological quality showed that the current evidence is at high risk of bias. Despite the high risk of bias, cadmium triggers significant lesions in the testis of murine models, regarding routes, in a dose- and time-dependent manner, mainly due to vascular changes. Therefore, cadmium is a risk factor for male reproductive health.
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Acknowledgments
The authors would like to thank Amanda Alves de Melo for English assistance, the support provided by Fundação do Amparo à Pesquisa do Estado de Minas Gerais (FAPEMIG, processes PPM-00687-17 and PPM-00077-18), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, processes 303972/2017-3, 423594/2018-4, 305093/2017-7, and MCTIC 408503/2018-1), and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, finance code 001). Also, we thank CAPES for the PhD scholarship provided to Silva J.
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da Silva, J., Gonçalves, R.V., de Melo, F.C.S.A. et al. Cadmium Exposure and Testis Susceptibility: a Systematic Review in Murine Models. Biol Trace Elem Res 199, 2663–2676 (2021). https://doi.org/10.1007/s12011-020-02389-0
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DOI: https://doi.org/10.1007/s12011-020-02389-0