4-Vinylcyclohexene diepoxide induces ovarian toxicity and oocyte damage in mice: mechanisms involving m6A/IGF2BP3-mediated meiotic mRNA stability regulation

This study investigates the role of m6A RNA methylation and IGF2BP3 in VCD-induced ovarian toxicity in mice. VCD exposure caused follicular depletion, oxidative stress, DNA damage, and meiotic defects in oocytes. Mechanistically, VCD altered m6A modifiers (METTL3, FTO, ALKBH5) and destabilized key meiotic mRNAs (e.g., Cenpa, Bub1, Polq) via IGF2BP3 downregulation, leading to spindle defects and chromosomal missegregation. Our findings reveal an m6A/IGF2BP3 axis as a critical mediator of environmental ovotoxicity.本研究探讨了N6-甲基腺嘌呤RNA甲基化（m6A RNA methylation）与胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）在VCD诱导的小鼠卵巢毒性模型中的作用。VCD暴露可导致小鼠卵母细胞出现卵泡耗竭、氧化应激、DNA损伤以及减数分裂缺陷。从机制层面分析，VCD可调控m6A修饰因子（METTL3、FTO、ALKBH5）的表达，并通过下调IGF2BP3破坏关键减数分裂相关mRNA（如Cenpa、Bub1、Polq）的稳定性，进而引发纺锤体缺陷与染色体分离错误。本研究结果揭示，m6A/IGF2BP3信号轴是环境性卵巢毒性的关键介导因子。