Impacts of di(2-ethylhexyl) terephthalate on multi-generational fitness of Caenorhabditis elegans via lipid metabolism and neural regulation

Di(2-ethylhexyl) terephthalate (DEHTP) is a substitutive plasticizer with various industrial applications. However, its wide occurrence in environmental matrices and human tissues is urging concerns on its toxicities. Presently, the effects of DEHTP on the fitness of Caenorhabditis elegans were explored with a consecutive exposure from F1 to F4 generations. The fitness was represented by reproduction, lifespan and behavior. Effects of DEHTP on reproduction showed an oscillation pattern with alteration from stimulation to inhibition and backwards. Influences of DEHTP on reproduction and lifespan showed trade-off relationships. Regarding behavior, DEHTP inhibited satiety quiescence duration, body bending and head swing, while stimulated reverse and Omega turns. At the biochemical level, DEHTP disturbed the lipid metabolites and lipid metabolism enzymes. Moreover, positive correlations were found between the effects on reproduction and with those on fatty acid synthase (FAS) and acyl-CoA (FA-CoA). DEHTP also disturbed the neural regulations including neural transmitters and the expressions of related genes. Out of expectation, the effects on neural regulations were positively correlated with those on lipid metabolism, but not with locomotion behavior. Hierarchical clustering analysis (HCA) results also indicated oscillatory changes underlying multi-generational effects of DEHTP, e.g., serotonin was more connected with other neural regulations than other indicators in F1 and F3, while it was more connected with behavior than others in F2 and F4.