Abstract：
Adverse outcome pathways (AOPs) are conceptual frameworks that organize knowledge about biological interactions and toxicity mechanisms. They present a sequence of events commencing with initial interaction(s) of a stressor, which defines the perturbation in a biological system (molecular initiating event, MIE), and a dependent series of key events (KEs), ending with an adverse outcome (AO). AOPs have recently become the subject of intense studies in a view to better understand the mechanisms of nanomaterial (NM) toxicity. Silver nanoparticles (Ag NPs) are one of the most explored nanostructures and are extensively used in various application. This, in turn, has increased the potential for interactions of Ag NPs with environments, and toxicity to human health. The aim of this study was to construct a putative AOPs (pAOP) related to reproductive toxicity of Ag NPs, in order to lay the groundwork for a better comprehension of mechanisms affecting both undesired toxicity (against human cell) and expected toxicity (against microorganisms).
PubMed and Scopus were systematically searched for peer-reviewed studies examining reproductive toxicity potential of Ag NPs. The quality of selected studies was assessed through ToxRTool. Eventually, forty-eight studies published between 2005 and 2022 were selected to identify the mechanisms of Ag NPs impact on reproductive function in human male. The biological endpoints, measurements, and results were extracted from these studies. Where possible, endpoints were assigned to a potential KE and an AO using expert judgment. Then, KEs were classified at each major level of biological organization.
We identified the impairment of intracellular SH-containing biomolecules, which are major cellular antioxidants, as a putative MIE, with subsequent KEs defined as ROS accumulation, mitochondrial damage, DNA damage and lipid peroxidation, apoptosis, reduced production of reproductive hormones and reduced quality of sperm. These successive KEs may result in impaired male fertility (AO).
This research recapitulates and schematically represents complex literature data gathered from different biological levels and propose a pAOP related to the reproductive toxicity induced by AgNPs. The development of AOPs specific to NMs should be encouraged in order to provide new insights to gain a better understanding of NP toxicity.
PubMed and Scopus were systematically searched for peer-reviewed studies examining reproductive toxicity potential of Ag NPs. The quality of selected studies was assessed through ToxRTool. Eventually, forty-eight studies published between 2005 and 2022 were selected to identify the mechanisms of Ag NPs impact on reproductive function in human male. The biological endpoints, measurements, and results were extracted from these studies. Where possible, endpoints were assigned to a potential KE and an AO using expert judgment. Then, KEs were classified at each major level of biological organization.
We identified the impairment of intracellular SH-containing biomolecules, which are major cellular antioxidants, as a putative MIE, with subsequent KEs defined as ROS accumulation, mitochondrial damage, DNA damage and lipid peroxidation, apoptosis, reduced production of reproductive hormones and reduced quality of sperm. These successive KEs may result in impaired male fertility (AO).
This research recapitulates and schematically represents complex literature data gathered from different biological levels and propose a pAOP related to the reproductive toxicity induced by AgNPs. The development of AOPs specific to NMs should be encouraged in order to provide new insights to gain a better understanding of NP toxicity.
摘要：
背景：不良结果途径（AOP）是组织有关生物相互作用和毒性机制知识的概念框架。他们提出了一系列事件，从压力源的初始相互作用开始，它定义了生物系统中的扰动(分子启动事件，MIE),和一系列依赖的关键事件(KEs)，以不良结果（AO）结束。为了更好地理解纳米材料（NM）毒性的机制，AOP最近已成为深入研究的主题。银纳米粒子(AgNPs)是探索最多的纳米结构之一,并且广泛用于各种应用中。这个,反过来,增加了AgNPs与环境相互作用的潜力，和对人体健康的毒性。本研究的目的是构建与AgNP生殖毒性相关的推定AOPs（pAOP），以便为更好地理解影响不希望的毒性（针对人类细胞）和预期毒性（针对微生物）的机制奠定基础。
方法：对PubMed和Scopus进行了系统搜索，以进行同行评审的研究，以检查AgNP的生殖毒性潜力。通过ToxRTool评估选定研究的质量。最终,选择了2005年至2022年之间发表的48项研究，以确定AgNP对人类男性生殖功能的影响机制。生物学终点，测量,并从这些研究中提取结果。在可能的情况下,使用专家判断将终点分配给潜在的KE和AO。然后，KEs在生物组织的每个主要级别进行分类。
结果：我们确定了细胞内含SH的生物分子的损伤，它们是主要的细胞抗氧化剂，作为推定的MIE,随后的KEs定义为ROS积累，线粒体损伤，DNA损伤和脂质过氧化，凋亡，减少生殖激素的产生和降低精子质量。这些连续的KE可能导致男性生育能力受损(AO)。
结论：这项研究概括并代表了从不同生物学水平收集的复杂文献数据，并提出了与AgNP诱导的生殖毒性相关的pAOP。应鼓励开发针对NM的AOP，以提供新的见解，以更好地了解NP毒性。
方法：对PubMed和Scopus进行了系统搜索，以进行同行评审的研究，以检查AgNP的生殖毒性潜力。通过ToxRTool评估选定研究的质量。最终,选择了2005年至2022年之间发表的48项研究，以确定AgNP对人类男性生殖功能的影响机制。生物学终点，测量,并从这些研究中提取结果。在可能的情况下,使用专家判断将终点分配给潜在的KE和AO。然后，KEs在生物组织的每个主要级别进行分类。
结果：我们确定了细胞内含SH的生物分子的损伤，它们是主要的细胞抗氧化剂，作为推定的MIE,随后的KEs定义为ROS积累，线粒体损伤，DNA损伤和脂质过氧化，凋亡，减少生殖激素的产生和降低精子质量。这些连续的KE可能导致男性生育能力受损(AO)。
结论：这项研究概括并代表了从不同生物学水平收集的复杂文献数据，并提出了与AgNP诱导的生殖毒性相关的pAOP。应鼓励开发针对NM的AOP，以提供新的见解，以更好地了解NP毒性。
