Reproductive toxicity and underlying mechanisms of di(2-ethylhexyl) phthalate in nematode Caenorhabditis elegans

Abstract DEHP (di(2-ethylhexyl) phthalate) is an endocrine disruptor commonly found in plastic products that has been associated with reproduction alterations, but the effect of DEHP on toxicity is still widely unknown. Using DEHP concentrations of 10, 1, and 0.1 mg/L, we showed that DEHP reduced the reproductive capacity of Caenorhabditis elegans after 72 hr. of exposure. DEHP exposure reduced the reproductive capacity in terms of decreased brood sizes, egg hatchability (0.1, 1 and 10 mg/L), and egg-laying rate (1 and 10 mg/L), and increased numbers of fertilized eggs in the uterus (1 and 10 mg/L). DEHP also caused damage to gonad development. DEHP decreased the total number of germline cells, and decreased the relative area of the gonad arm of all exposure groups, with worms in the 1 mg/L DEHP exposure group having the minimum gonad arm area. Additionally, DEHP caused a significant concentration‐dependent increase in the expression of unc-86. Autophagy and ROS contributed to the enhancement of DEHP toxicity in reducing reproductive capacity, and glutathione peroxidase and superoxide dismutase were activated as the antioxidant defense in this study. Hence, we found that DEHP has a dual effect on nematodes. Higher concentration (10 mg/L) DEHP can inhibit the expression of autophagy genes (atg-18, atg-7, bec-1, lgg-1 and unc-51), and lower concentrations (0.1 and 1 mg/L) can promote the expression of autophagy genes. Our data highlight the potential environmental risk of DEHP in inducing reproductive toxicity toward the gonad development and reproductive capacity of environmental organisms.