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. Overall design: 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.