The Adverse Effect Of TCIPP And TCEP On Neurodevelopment Of Zebrafish Embryos/larvae

Objective : Organophosphorus flame retardants(OPFRs)are mass produced chemicals,mainly used as replacements for brominated flame retardants.TCEP and TCIPP were two kinds of typical chlorinated OPFRs,which were commonly detected in various environmental medium.Here,TCEP and TCIPP were seltected to investigate the adverse effects on the early neural development of zebrafish.Methods:Zebrafish embryos(within 2 hours post fertilization [hpf])were exposed to different concentrations of TCEP and TCIPP(0,100,500 or 2500 ?g/L)until 120 h.The typical neurotoxic substance chlorpyrifos(CPF,100 ?g/L)was used as a positive control.The growth and developmental index,such as 72 hpf hatching rate,96 h mortality rate and deformity rate were determined,and the motility behavior,acetylcholine content and acetylcholinesterase activity,central nervous system development related genes(such as: ?1-tubulin,mbp,syn2?,gfap,shha,ache and gap43)and proteins of zebrafish larvae were also measured to comprehensively evaluate the effects of TCEP and TCIPP on the early neurodevelopment of zebrafish,and also compared with CPF.Result:The results showed that CPF(positive control)induced developmental toxicity(including inhibition of growth,reduction of hatching rate and surival rate,and increase in malformation).At the same time,it also caused inhibition of locomotor activity in dark stimulation.Comparative studies found that low and medium concentrations of TCIPP and TCEP had no significant effect on the development and locomotor activity in zebrafish larvae,but high concentrations of TCIPP and TCEP caused developmental toxicity.Besides,TCEP and TCIPP also inhibition the locomotor activity in dark period.Our results showed that TCEP and TCIPP caused developmental toxicity and inhibition the locomotor activity in dark periods,but the potentiation is less than CPF.Further,our results also showed that TCIPP and TCEP had no effect on acetylcholine content and AChE activity,but CPF significantly increased acetylcholine content and inhibited AChE activity.Finally,the detection of key genes and proteins related to central nervous system development showed that TCIPP,TCEP and CPF all significantly inhibited the expression of genes and proteins involved in neurodevelopment(such as mbp,syn2 a and ?1-tubulin).In addition,TCIPP and TCEP can also affect the transcription of shha and gap43,but CPF has no effect on shha and gap43.Conclusion:Our results indicated that TCIPP and TCEP may have adverse effects on the neurodevelopment of zebrafish embryos/larvae,mainly affect the expression of genes and proteins related to central nervous development.The underlying mechanism maybe different from typical neurotoxic(CPF),which is not related to acetylcholinesterase inhibition.