Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China; Guangdong Provincial Key Laboratory of Tumor Interventional Diagnosis and Treatment, Zhuhai Institute of Translational Medicine, Zhuhai People's Hospital Affiliated with Jinan University, Jinan University, Zhuhai 519000, Guangdong, China; The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou 510632, Guangdong, China.
Department of Pathogen Biology, School of Medicine, Jinan University, Guangzhou 510632, Guangdong, China; The Biomedical Translational Research Institute, Faculty of Medical Science, Jinan University, Guangzhou 510632, Guangdong, China.
Environ Int. 2024 Sep;191:108952. doi: 10.1016/j.envint.2024.108952. Epub 2024 Aug 14.
Cadmium is a significant environmental pollutant that poses a substantial health hazard to humans due to its propensity to accumulate in the body and resist excretion. We have a comprehensive understanding of the damage caused by Cd exposure and the mechanisms of tolerance, however, the intricate mechanisms underlying multigenerational effects resulting from Cd exposure remain poorly understood. In this study, Caenorhabditis elegans were used as a model organism to investigate Cd-induced multigenerational effects and its association with epigenetic modifications. The results showed that Cd exposure leads to an increase in germ cell apoptosis and a decrease in fertility, which can be passed down to subsequent generations. Further analysis revealed that transcription factors DAF-16/FOXO and SKN-1/Nrf2 play essential roles in responding to Cd exposure and in the transgenerational induction of germ cell apoptosis. Additionally, histone H3K4 trimethylation (H3K4me3) marks stress-responsive genes and enhances their transcription, ultimately triggering multigenerational germ cell apoptosis. This study provides compelling evidence that the detrimental effects of Cd on the reproductive system can be inherited across generations. These findings enhance our understanding of the multigenerational effects of environmental pollutants and may inform strategies for the prevention and control of such pollutants.
镉是一种重要的环境污染物,由于其在体内积累和不易排出的特性,对人类健康构成了重大威胁。我们对镉暴露造成的损害以及耐受机制有了全面的了解,但对于镉暴露导致的多代效应的复杂机制仍知之甚少。在这项研究中,秀丽隐杆线虫被用作模型生物来研究镉诱导的多代效应及其与表观遗传修饰的关系。结果表明,镉暴露会导致生殖细胞凋亡增加和生育力下降,这些效应可以传递给后代。进一步的分析表明,转录因子 DAF-16/FOXO 和 SKN-1/Nrf2 在应对镉暴露和跨代诱导生殖细胞凋亡中发挥着重要作用。此外,组蛋白 H3K4 三甲基化(H3K4me3)标记应激反应基因并增强其转录,最终引发多代生殖细胞凋亡。这项研究提供了确凿的证据,表明镉对生殖系统的有害影响可以在几代人之间遗传。这些发现加深了我们对环境污染物多代效应的理解,并可能为预防和控制此类污染物提供策略。