Effects of long-term exposure to TDCPP in zebrafish( Danio rerio )–Alternations of hormone balance and gene transcriptions along hypothalamus-pituitary axes

Background : TDCPP is one of the major chemical of organophosphate flame retardants(OPFRs) that has been detected ubiquitously in both the environment and biota. Previously we observed that it influenced the concentrations of sex and thyroid hormones in a sex-dependent pattern, leading to reproductive impairments after short-term exposure in zebrafish. Here we investigate the consequences of longerterm exposure to TDCPP on the hypothalamic-pituitary-gonad(HPG), hypothalamicpituitary-i nterrenal(HPI), and hypothalamic-pituitary-thyroid(HPT) axes of zebrafish( Danio rerio).Methods : A 120-day exposure test to 0.005, 0.05 and 0.5 mg/L TDCPP was initiated with fertilized eggs. Sex steroid hormones in the treated fishes were measured and transcriptional changes were analyzed.Results : In female fish, exposure to TDCPP resulted in increases in plasma cortisol,follicle stimulating hormone(FSH), luteinizing hormone(LH), 17β-estradiol(E2), cortisol, thyroxine(T4), and triiodothyronine(T3). Transcription of most target genes along HPG, HPI and HPT axes were increased by the exposure. While in male fish the exposure led to decreases in cortisol, FSH, LH, T4, T3, testosterone(T), and 11-ketotestosterone(11-KT). Transcription of genes along HPG, HPI and HPT axes,especially steroidogenic genes, were inhibited in male zebrafish. While, E2/T or E2/11-KT ratio was increased in both female and females. The sex-dependent changes in hormones might be due to differential responses to TDCPP induced stresses. An increase in cortisol level coincided with increases in E2 and THs in female fish, while in males decreases in cortisol as well as T, 11-KT and THs were observed. Long-term exposure to TDCPP at very low(μg/L) concentrations could disrupt hormone balances in a sex dependent way.Conclusion : This study revealed that TDCPP could affect endocrine axes – HPG, HPI and HPT – in zebrafish, and impair zebrafish development.