Tris(1,3-dichloro-2-propyl)phosphate Reduces Growth Hormone Expression via Binding to Growth Hormone Releasing Hormone Receptors and Inhibits the Growth of Crucian Carp

Tris(1,3-dichloro-2-propyl)phosphate (TDCIPP) has commonly been used as an additive flame retardant and frequently detected in the aquatic environment and in biological samples worldwide. Recently, it was found that exposure to TDCIPP inhibited the growth of zebrafish, but the relevant molecular mechanisms remained unclear. In this study, 5 day-old crucian carp (Carassius auratus) larvae were treated with 0.5, 5, or 50 μg/L TDCIPP for 90 days; the effect on growth was evaluated; and related molecular mechanisms were explored. Results demonstrated that 5 or 50 μg/L TDCIPP treatment significantly inhibited the growth of crucian carp and downregulated the expression of growth Hormones (ghs), growth hormone receptor (ghr), and insulin-like growth factor 1 (igf1). Molecular docking, dual-luciferase reporter gene assay, and in vitro experiments demonstrated that TDCIPP could bind to the growth hormone releasing hormone receptor protein of crucian carp and disturb the stimulation of growth hormone releasing hormone to the expression of ghs, resulting in the decrease of the mRNA level of gh1 and gh2 in pituitary cells. Our findings provide new perceptions into the molecular mechanisms of developmental toxicity of TDCIPP in fish.