Effects of tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and triphenyl phosphate (TPP) on sex-dependent alterations of thyroid hormones in adult zebrafish

Organophosphate flame retardants (OPFRs) have been widely used as alternatives to polybrominated diphenyl ethers for fire prevention. OPFRs are suspected of causing potential thyroid disruption in humans. In fish, their thyroid hormone modulation is reported but the mechanisms of this modulation are less understood. Thyroid-disturbing effects of OPFRs were evaluated using adult zebrafish (Danio rerio) following 14d exposure to tris(1,3-dichloro-2-propyl) phosphate (TDCPP) or triphenyl phosphate (TPP). Plasma concentrations of thyroid hormones were measured and transcriptions of several genes involved in thyroid function were quantified in brain, thyroid, and liver. Exposure to TDCPP or TPP led to significant decreases in plasma triiodothyronine (T3) and thyroxine (T4) concentrations in the male fish, while the increases were observed in the female fish. Exposure to the OPFRs also altered the transcription of regulatory genes and receptors in hypothalamus, pituitary, and thyroid of the fish in sex-dependent manner. In the male fish, transcriptions of corticotropin-releasing hormone (crh) and thyroid-stimulating hormone (tsh) in the brain were significantly up-regulated, probably as a compensation for hypothyroidism, but thyroglobulin (tg) and deiodinase 2 (dio2) were down-regulated in thyroid or liver. In contrast, in the females, transcriptions of crh and tsh genes were significantly down-regulated. These observations show that TDCPP and TPP exposure can lead to sex-dependent disruptions of thyroid hormone balances in the adult zebrafish through alterations of the hypothalamus-pituitary-thyroid (HPT) axis.