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

Abstract

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.

Growth Retardation in Silver Carp (Hypophthalmichthys molitrix) in the Middle Reaches of the Yangtze River and its Possible Causal Agents

“…For example, exposure to environmentally relevant concentration of tris(1,3dichloro-2-propyl) phosphate could inhibit the growth of crucian carp and zebrafish by influencing the transcription of growth-related genes. 19 Moreover, an obvious growth inhibition was observed in zebrafish exposed to tris(2-butoxyethyl) phosphate for 90 days. 23 However, the actual impacts of OPEs at environmentally observed concentrations on the growth of wild fish are still largely unknown.…”

“…Furthermore, a total of 12 OPEs were detected in the fish samples from the Pearl River Delta, with concentrations of 2.3–30 ng/g wet weight . Extensive studies reported that OPEs induced various adverse health effects on nontarget organisms in laboratory-controlled experiments, including the developmental toxicity, hepatotoxicity, genotoxicity, and reproductive toxicity, − and developmental retardation was considered a major toxic effect. For example, exposure to environmentally relevant concentration of tris­(1,3-dichloro-2-propyl) phosphate could inhibit the growth of crucian carp and zebrafish by influencing the transcription of growth-related genes .…”

“…Extensive studies reported that OPEs induced various adverse health effects on nontarget organisms in laboratory-controlled experiments, including the developmental toxicity, hepatotoxicity, genotoxicity, and reproductive toxicity, − and developmental retardation was considered a major toxic effect. For example, exposure to environmentally relevant concentration of tris­(1,3-dichloro-2-propyl) phosphate could inhibit the growth of crucian carp and zebrafish by influencing the transcription of growth-related genes . Moreover, an obvious growth inhibition was observed in zebrafish exposed to tris­(2-butoxyethyl) phosphate for 90 days .…”

Environmentally Relevant Concentrations of Tris(1,3-dichloro-2-propyl) Phosphate Induced a Female-Biased Osteotoxicity in Crucian Carp (Carassius auratus)

“…During production and usage, nearly 10% of the added TDCIPP was released and escaped into the environment . Environmental monitoring data suggested that TDCIPP was distributed in the aquatic environments worldwide . For example, in natural waters, the concentrations of TDCIPP ranged from less than the detection limit to 2359 ng/L. − Relatively great concentrations of TDCIPP were also detected in the wild fish.…”

“…Crucian carp ( Carassius auratus ) has a wide distribution in the freshwater system in China and has been applied as a potential model organism to evaluate adverse effects of chemical pollutants in natural aquatic environments. , Compared with laboratory small fish, such as zebrafish or medaka ( Oryzias latipes ), crucian carp has a longer life span and would suffer a longer exposure period in natural contaminated water, which might suffer great environment hazards. A previous study showed that exposure to environmentally relevant concentrations of TDCIPP changed the expressions of skeleton-related genes in zebrafish, but no morphological changes in the skeleton were observed .…”