Abstract：
As a member of biodegradable plastics, exposure risk of polylactic acid microplastic (PLA-MP) has received attention recently. Toxicity of PLA-MP at parental generation (P0-G) has been observed in some organisms; however, its possible transgenerational toxicity and underlying mechanisms remain unclear. In Caenorhabditis elegans, 10 and 100 μg/L PLA-MP resulted in transgenerational inhibition in reproductive capacity and transgenerational damage on gonad development. Meanwhile, transgenerational increase in germline apoptosis was detected after PLA-MP exposure at P0-G, which was associated with transgenerational dysregulation in expressions of genes governing apoptosis (ced-3, ced-4, egl-1, and ced-9) and DNA damage related genes (cep-1, mrt-2, hus-1, and clk-2). Among secreted ligand genes, PLA-MP exposure induced transgenerational increase in expression of ins-39 and wrt-3, and RNAi of ins-39 and wrt-3 inhibited germline apoptosis in PLA-MP exposed nematodes. Additionally, PLA-MP caused transgenerational increase in expression of met-2 and set-6 encoding histone methylation transferases, and germline apoptosis induced by PLA-MP could be suppressed by RNAi of met-2 and set-6. Dysregulated expressions of some apoptosis and DNA damage related genes caused by PLA-MP were reversed by RNAi of ins-39, wrt-3, met-2, and set-6. Moreover, in PLA-MP exposed animals, expression of ins-39 and wrt-3 could be further inhibited by RNAi of met-2 and set-6. Therefore, PLA-MP potentially induced reproductive toxicity across multiple generations, which was under the control of MET-2 and SET-6 activated ligands of INS-39 and WRT-3.
摘要：
作为生物降解塑料的一员,聚乳酸微塑料（PLA-MP）的暴露风险最近受到关注。在某些生物体中观察到了亲代（P0-G）时PLA-MP的毒性；然而，其可能的跨代毒性和潜在机制尚不清楚.在秀丽隐杆线虫中,10和100μg/LPLA-MP导致生殖能力的跨代抑制和性腺发育的跨代损伤。同时,在P0-G暴露于PLA-MP后检测到种系凋亡的代际增加，这与控制凋亡的基因（ced-3，ced-4，egl-1和ced-9）和DNA损伤相关基因（cep-1，mrt-2，hus-1和clk-2）的跨代表达失调有关。在分泌的配体基因中，PLA-MP暴露诱导ins-39和wrt-3表达的跨代增加，而ins-39和wrt-3的RNAi抑制PLA-MP暴露线虫的种系凋亡。此外,PLA-MP引起编码组蛋白甲基化转移酶的met-2和set-6表达的跨代增加，PLA-MP诱导的种系凋亡可被met-2和set-6的RNAi抑制。由PLA-MP引起的某些凋亡和DNA损伤相关基因的表达失调被ins-39，wrt-3，met-2和set-6的RNAi逆转。此外，在PLA-MP暴露的动物中，met-2和set-6的RNAi可以进一步抑制ins-39和wrt-3的表达。因此,PLA-MP可能在多代中诱导生殖毒性，在INS-39和WRT-3的MET-2和SET-6激活的配体的控制下。
