Multigenerational exposure to silver ions and silver nanoparticles reveals heightened sensitivity and epigenetic memory in Caenorhabditis elegans

The effects from multigenerational exposures to engineered nanoparticles (ENPs) in their pristine and transformed states are currently unknown despite such exposures being an increasingly common scenario in natural environments. Here, we examine how exposure over 10 generations affects the sensitivity of the nematode Caenorhabditis elegans to pristine and sulfidized Ag ENPs and AgNO3. We also include populations that were initially exposed over six generations but kept unexposed for subsequent four generations to allow recovery from exposure. Toxicity of the different silver forms decreased in the order AgNO3, Ag ENPs and Ag2S ENPs. Continuous exposure to Ag ENPs and AgNO3 caused pronounced sensitization (approx. 10-fold) in the F2 generation, which was sustained until F10. This sensitization was less pronounced for Ag2S ENP exposures, indicating different toxicity mechanisms. Subtle changes in size and lifespan were also measured. In the recovery populations, the sensitivity to Ag ENPs and AgNO3 resulting from the initial multigenerational exposure persisted. Their response sensitivity for all endpoints was most closely related to the last ancestral exposed generation (F5), rather than unexposed controls. The mechanisms of transgenerational transfer of sensitivity are probably organized through the epigenome, and we encourage others to investigate such effects as a priority for mechanistic toxicology.

尽管工程纳米颗粒（engineered nanoparticles, ENPs）在自然环境中的暴露场景愈发普遍，但其原始态与转化态所引发的多代生物暴露效应目前仍未明确。本研究以秀丽隐杆线虫（Caenorhabditis elegans）为模型，探究10代持续暴露对其暴露于原始态银工程纳米颗粒、硫化态银工程纳米颗粒以及硝酸银（AgNO3）时的敏感性影响。此外，本研究设置了初始暴露6代后暂停暴露4代以实现暴露清除的恢复种群作为对照群体。不同银基制剂的毒性强弱依次为硝酸银、银工程纳米颗粒与硫化态银工程纳米颗粒（Ag₂S ENPs）。持续暴露于银工程纳米颗粒与硝酸银会使F2代线虫产生约10倍的敏感性升高，且该效应可持续至F10代；而硫化态银工程纳米颗粒暴露引发的敏感性升高效应相对较弱，提示二者的毒性机制存在差异。本研究同时检测到线虫体型与寿命的细微变化。在恢复种群中，初始多代暴露所导致的线虫对银工程纳米颗粒与硝酸银的敏感性依然保留，其各项检测终点的响应敏感性与末次祖先暴露代（F5）最为接近，而非未暴露的对照组。这种敏感性跨代传递的机制可能通过表观基因组（epigenome）调控，我们呼吁学界优先开展相关机制毒理学研究以阐明该现象。