The plasticizer di(2-ethylhexyl) phthalate (DEHP) is an emerging organic contaminant that has represented a risk for organisms present in the environment. However, there is still limited information regarding DEHP-induced multigenerational toxicity and the underlying mechanisms. In this study we investigated the multigenerational toxic effects including locomotive behaviors and reproduction upon prolonged DEHP exposure (from larval L1 to adult) and the underlying mechanisms in the nematode Caenorhabditis elegans. The multigenerational effects were examined over 6 generations (F0–F5) with only parental C. elegans (F0) was exposed to DEHP from larval L1 to adults (72 h), and the subsequent offsprings (F1–F5) were grown under DEHP-free conditions. The results showed that prolonged exposure (72 h) to various concentrations of DEHP caused dose-dependent locomotive impairments and reproduction defects in C. elegans and that a concentration of 0.2 mg/L DEHP was enough to cause such sublethal effects. The results showed that after prolonged exposure to DEHP in the F0 generation, abnormal locomotive behaviors such as reduced body bends and head thrashes were observed from generations F0 to F5. Additionally, prolonged exposure to DEHP (20 mg/L) in F0 significantly reduced total brood size in F0, and this parental exposure was sufficient to cause multigenerational reproductive toxicity in the offspring generations (F1–F5) as well. Furthermore, the expressions of reproduction-related genes such as vit-2 and vit-6 were down-regulated by about 20% until F3, and the expression of H3Kme2 demethylase, spr-5, was downregulated in F1 by about 40%. Results from this study demonstrate that prolonged exposure to DEHP only at F0 adversely affected reproduction and locomotive behaviors in C. elegans across generations and might be associated with inadequate vitellogenin production and malfunction of H3Kme2 demethylase. This study implies that parentally prolonged exposure to DEHP caused multigenerational defects in both reproduction and locomotive behaviors raising the potential health and ecological risk.

增塑剂邻苯二甲酸二（2-乙基己基）酯（DEHP）是一种新兴的有机污染物，对环境中存在的有机物构成了风险。但是，关于DEHP诱导的多代毒性及其潜在机制的信息仍然有限。在这项研究中，我们研究了多代毒性作用，包括长期DEHP暴露（从幼虫L1到成虫）的机车行为和繁殖，以及线虫秀丽隐杆线虫的潜在机制。仅通过亲代秀丽隐杆线虫检查了6代以上的多代效应（F0–F5）（F0）从幼虫L1暴露于成年幼虫（72 h），随后的后代（F1-F5）在无DEHP的条件下生长。结果表明，在不同浓度的DEHP中长时间暴露（72小时）会导致秀丽隐杆线虫的剂量依赖性机车损伤和繁殖缺陷。并且0.2 mg / L的DEHP浓度足以引起这种亚致死作用。结果表明，在F0代中长时间暴露于DEHP后，从F0到F5代观察到异常的机车行为，例如减少的身体弯曲和头部head打。此外，在F0中长期暴露于DEHP（20 mg / L）会显着降低F0中的总亲鱼大小，这种亲本暴露也足以在后代（F1-F5）中引起多代生殖毒性。此外，直到F3为止，与繁殖相关的基因如vit-2和vit-6的表达下调了约20％，而H3Kme2脱甲基酶spr-5的表达下调了。在F1中被下调了约40％。这项研究的结果表明，仅在F0长时间暴露于DEHP会对线虫的代代繁殖和机车行为产生不利影响，并且可能与卵黄蛋白原产量不足和H3Kme2脱甲基酶功能异常有关。这项研究表明，父母长期暴露于DEHP会导致繁殖和机车行为的多代缺陷，从而增加潜在的健康和生态风险。