College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.
Guangling College, Yangzhou University, Yangzhou 225000, China.
Int J Mol Sci. 2024 Oct 12;25(20):10996. doi: 10.3390/ijms252010996.
Maternal cadmium exposure during pregnancy has been demonstrated to have detrimental effects on offspring development. However, the impact of maternal cadmium exposure on offspring oocytes remains largely unknown, and the underlying mechanisms are not fully understood. In this study, we found that maternal cadmium exposure during pregnancy resulted in selective alteration in epigenetic modifications of mouse oocytes in offspring, including a decrease in H3K4me2 and H4K12ac, as well as an increase in DNA methylation of . Although ROS levels and mitochondrial activity remain at normal levels, the DNA damage marker γH2AX was significantly increased and the DNA repair marker DNA-PKcs was remarkably decreased in offspring oocytes from maternal cadmium exposure. These alterations are responsible for the decrease in the quality of mouse oocytes in offspring induced by maternal cadmium exposure. As a result, the meiotic maturation of oocytes and subsequent early embryonic development are influenced by maternal cadmium exposure. RNA-seq results showed that maternal cadmium exposure elicits modifications in the expression of genes associated with metabolism, signal transduction, and endocrine regulation in offspring ovaries, which also contribute to the disorders of oocyte maturation and failures in early embryonic development. Our research provides direct evidence of transgenerational epigenetic inheritance of cadmium reproductive toxicity in mouse germ cells.
母体妊娠期间的镉暴露已被证实对后代发育有不良影响。然而，母体镉暴露对子代卵母细胞的影响在很大程度上仍然未知，其潜在机制也尚未完全阐明。在本研究中，我们发现母体妊娠期间的镉暴露导致子代卵母细胞中表观遗传修饰的选择性改变，包括 H3K4me2 和 H4K12ac 的减少，以及 的 DNA 甲基化增加。尽管 ROS 水平和线粒体活性仍保持在正常水平，但γH2AX 的 DNA 损伤标志物显著增加，而 DNA-PKcs 的 DNA 修复标志物则明显减少。这些改变是母体镉暴露导致子代卵母细胞质量下降的原因。因此，母体镉暴露影响卵母细胞的减数分裂成熟和随后的早期胚胎发育。RNA-seq 结果表明，母体镉暴露引起子代卵巢中与代谢、信号转导和内分泌调节相关的基因表达发生改变，这也导致卵母细胞成熟障碍和早期胚胎发育失败。我们的研究为镉生殖毒性在小鼠生殖细胞中的跨代表观遗传遗传提供了直接证据。
