Putative adverse outcome pathways for silver nanoparticle toxicity on mammalian male reproductive system: a literature review

Abstract

Background 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). Methods 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. Results 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). Conclusion 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.

Histological Effect of Green Synthesized Silver Nanoparticles Agnps on Albino Rat Testis

“…Ag-NPs' toxicity may act at these stages to cause the apoptosis of germ cells in the testis, which would result in lower testosterone levels (33) . The loss of spermatogenic cell that noticed in our sections may explained by the ability of Ag-NPs to pass the blood testicular barrier, and travel to the seminiferous tubules, where they might influence sperm production and quality (34)(35)(36) . The histopathologic alterations that observed in individual that treated with Ag NPs may related to Sertoli cell disfunctions and Leydig cells inhibiting testosterone synthesis efficiency.…”

Physicochemical Transformations of Silver Nanoparticles in the Oro-Gastrointestinal Tract Mildly Affect Their Toxicity to Intestinal Cells In Vitro: An AOP-Oriented Testing Approach

“…This AOP ends with AO lung tissue damage. Finally, we recently described a putative AOP linking the MIE Impairment of intracellular SH-containing biomolecules to impaired fertility in human males [ 41 ]. This AOP includes eight KEs, the earliest being mitochondrial damage, ROS accumulation, oxidative stress, lipid peroxidation, DNA damage, apoptosis in Leydig cells and the latest being related to damage to the male reproductive system and therefore not relevant to the present work.…”

“… AOPs reporting Ag NPs as a potential stressor. Four AOPs showing Ag NPs as stressors were analyzed in terms of their molecular initiating events (MIE, green boxes), key events (KE, yellow boxes) and adverse outcomes (AO, orange boxes) [ 38 , 39 , 40 , 41 ]. This led to the identification of several pathways that are shared among these AOPs (highlighted in grey), focusing on oxidative stress, DNA damage and repair, and apoptosis.…”

Gold and silver nanoparticles in Alzheimer's and Parkinson's diagnostics and treatments

“…In fact, AgNPs tend to ionize upon internalization, causing the release of silver ions within the cell cytoplasm, activating the production of ROS, and causing mitochondrial damage. These pathways can then lead to cell death by apoptotic processes or necrosis 97–99 . AgNPs have been demonstrated to reach the brain thanks to their intrinsic ability to cross the BBB, 100 while their adsorption in the body usually happens through environmental exposure (like inhalation or skin contact) 101 …”

“…These pathways can then lead to cell death by apoptotic processes or necrosis. [97][98][99] AgNPs have been demonstrated to reach the brain thanks to their intrinsic ability to cross the BBB, 100 while their adsorption in the body usually happens through environmental exposure (like inhalation or skin contact). 101 In addition to astrocytes, the brain is equipped with microglia, namely tissue-resident macrophages that orchestrate the active immune defense against invading pathogens in the central nervous system.…”