Photo-aged polylactic acid microplastics causes severe transgenerational decline in reproductive capacity in C. elegans: Insight into activation of DNA damage checkpoints affected by multiple germline histone methyltransferases

At parental generation (P0-G), photo-aged polylactic acid microplastics (PLA-MPs) could cause severe toxicity on nematodes. However, their transgenerational toxicity and underlying mechanism remain largely unknown. Severe transgenerational decline in reproductive capacity was observed in nematodes after exposure to 1-100 μg/L photo-aged PLA-MPs. This transgenerational reproductive toxicity was not related to leachates of photo-aged PLA-MPs, and only partially related to their transgenerational accumulation. The photo-aged PLA-MPs caused transgenerational decline in reproductive capacity was associated with transgenerational reduction in mitotic cell number in gonads and germline apoptosis induction. As upregulators of genes governing germline apoptosis, transgenerational activation of DNA damage checkpoint was induced by photo-aged PLA-MPs. Moreover, after photo-aged PLA-MPs exposure, 9 germline histone methyltransferase (HMTs) genes were identified to exhibit transgenerational change of their expressions. Among them, photo-aged PLA-MPs induced germline apoptosis and DNA damage checkpoint activation were strengthened by mes-2, set-27, set-24, set-28, set-31, and set-2 RNAi, and suppressed by met-2, set-3, and set-6 RNAi. Therefore, our results suggested exposure risk of photo-aged PLA-MPs in the range of μg/L in inducing severe transgenerational toxicity on reproductive capacity, which was driven by germline HMTs controlled DNA damage checkpoints activation.