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.

中文翻译：

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镉暴露和睾丸易感性：小鼠模型的系统评价。

众所周知，镉会导致睾丸损伤。然而，镉对睾丸结构的显着影响以及该过程中涉及的机制尚不清楚。此外，剂量、途径和接触时间与伤害之间的关系仍然知之甚少。因此，我们旨在评估任何剂量、途径和时间的镉暴露是否会导致小鼠模型睾丸组织的显着改变，以及所涉及的主要机制。我们对 Medline/PubMed 和 Scopus 数据库进行了结构化搜索，以检索 2018 年 9 月之前发表的研究。结果被组织到一个不良结局途径 (AOP) 框架中。此外，对纳入研究进行了偏倚分析。我们纳入了 37 项研究，并且他们中的大多数以剂量和时间依赖性方式确定了小管和小管间有关途径的重要组织病理学。在暴露的最初几个小时后观察到损伤，主要是血管损伤，表明脉管系统衰竭是主要机制。AOP 表明，潜在的分子启动事件可能会模拟和干扰破坏蛋白质（结构和抗氧化剂）、氧化磷酸化酶活性变化和基因表达改变的基本元素，从而导致生殖失败（不利结果）。方法学质量分析表明，当前证据存在高偏倚风险。尽管存在较高的偏倚风险，但镉会以剂量和时间依赖性方式在小鼠模型的睾丸中引发显着病变，关于途径，主要是由于血管变化。因此，镉是男性生殖健康的危险因素。