Effects of di-(2-ethylhexyl) terephthalate on hypothalamus-pituitary-gonad axis in adult zebrafish.

Di-(2-ethylhexyl) terephthalate (DEHTP) is frequently used in food packaging and medical devices as an alternative to di-(2-ethylhexyl) phthalate (DEHP). In this study, zebrafish pairs were exposed to DEHTP for 21 d and the effects on fertility, sex hormone levels, vitellogenin levels, and transcription of genes along the hypothalamic-pituitary-gonad axis were evaluated. Results showed that mean egg numbers were significantly reduced in the 30 and 300 μg/L DEHTP groups. The adverse effects of DEHTP on hormones and gene transcripts were more prominent in males than in females. In male fish, the gonadosomatic index, hepatosomatic index, and vitellogenin concentration were significantly increased. The results of a significant decrease in testosterone (T) and an increase in the 17β-estradiol (E2)/T ratio in males exposed to 3-300 μg/L DEHTP suggest that the endocrine potential of DEHTP is similar that of DEHP. In females, genes related to gonadotropin-releasing hormone and gonadotropin were up-regulated while E2 was significantly down-regulated. These findings suggest that positive E2 feedback mechanisms in the hypothalamus and pituitary gland are activated to balance sex hormones. The effects of chronic exposure to DEHTP on the neuroendocrine system require further investigation.