Institute of Food Safety and Health, College of Public Health, National Taiwan University, Taipei 10055, Taiwan.
Institute of Food Safety and Health, College of Public Health, National Taiwan University, Taipei 10055, Taiwan; Department of Public Health, College of Public Health, National Taiwan University, Taipei, 10055, Taiwan.
Environ Pollut. 2024 Nov 15;361:124787. doi: 10.1016/j.envpol.2024.124787. Epub 2024 Aug 23.
Zearalenone (ZEN), an endocrine-disrupting mycotoxin, is prevalent and persists in the environment. ZEN has the potential to cause adverse health impacts extending over generations, yet there is a lack of relevant research. Therefore, we explored the ZEN-induced multi-/trans-generational locomotive and reproductive toxicities, as well as the underlying epigenetic mechanisms in Caenorhabditis elegans. In multi-generational analysis, the evolution tendency and toxicity latency were observed under sustained exposure to 0.1 and 1 μM ZEN across five generations (P0-F4). The toxic effects were found in filial generations even if the initial parental exposure showed no apparent effects. Trans-generational results indicated the toxic inheritance phenomenon of 10 and 50 μM ZEN, where a single generation of ZEN exposure was sufficient to affect subsequent generations (F1-F3). Additionally, the pattern of locomotion was relatively sensitive in both generational studies, indicating varying sensitivity between indicators. Regarding epigenetic mechanism of toxicity transmission, ZEN significantly decreased the parental expression of histone methyltransferase encoded genes set-2, mes-2, and mes-4. Notably, the downregulation of mes-4 persisted in the unexposed F1 and F2 generations under trans-generational exposure. Furthermore, the mes-4 binding and reproduction-related rme-2 also decreased across generations. Moreover, parental germline specific knockdown of mes-4 eliminated the inherited locomotive and reproductive toxic effects in offspring, showing that mes-4 acted as transmitter in ZEN-induced generational toxicities. These findings suggest that ZEN is an epigenetic environmental pollutant, with a possible genetic biomarker mes-4 mediating the germline dependent transmission of ZEN-triggered toxicity over generations. This study provides significant insights into ZEN-induced epigenotoxicity.
玉米赤霉烯酮（ZEN）是一种内分泌干扰霉菌毒素，普遍存在于环境中并能长期存在。ZEN 有可能对代际健康产生不利影响，但目前相关研究还很缺乏。因此，我们在秀丽隐杆线虫中探索了 ZEN 引起的多/跨代运动和生殖毒性，以及潜在的表观遗传机制。在多代分析中，我们观察到在持续暴露于 0.1 和 1 μM ZEN 时，跨五代（P0-F4）的进化趋势和毒性潜伏期。即使初始亲代暴露没有明显影响，也会在子代中发现毒性作用。跨代结果表明，10 和 50 μM ZEN 存在毒性遗传现象，单次 ZEN 暴露足以影响后续几代（F1-F3）。此外，在两代研究中，运动模式相对敏感，表明不同指标的敏感性存在差异。关于毒性传递的表观遗传机制，ZEN 显著降低了组蛋白甲基转移酶编码基因 set-2、mes-2 和 mes-4 的亲代表达。值得注意的是，在跨代暴露下，未暴露的 F1 和 F2 代中 mes-4 的下调持续存在。此外，mes-4 与生殖相关的 rme-2 也在各代中减少。此外，亲代生殖细胞特异性敲低 mes-4 可消除后代中遗传的运动和生殖毒性作用，表明 mes-4 作为 ZEN 诱导的代际毒性的传递者发挥作用。这些发现表明，ZEN 是一种表观遗传环境污染物，其遗传生物标志物 mes-4 可能介导 ZEN 引发的毒性通过生殖系在代际间的传递。本研究为 ZEN 诱导的表观遗传毒性提供了重要的见解。
