Disruption Of The Thyroid Endocrine In Zebrafish Exposure To Penta-polybrominated Biphenyl Ethers (BDE-99)

Polybrominated diphenyl ethers(PBDEs)belongs to a family of man-made compounds widely used as brominated flame retardants due to their unique physical and chemical nature.2,2',4,4',5-Pentabromodiphenyl ether(BDE-99)is main domain congeners of PBDE and were detected in human being blood and breast milk.zebrafish embryos model was tested.In order to reveal these mechanisms',zebrafish(Danio rerio)were exposed to different concentrations of BDE-99.1.2,2',4,4',5-Pentabromodiphenyl ether(BDE-99)causes thyroid disruption and neurotoxicity,but the underlying mechanisms for this remain unclear in fish.To explore the potential mechanism of thyroid dysfunction and neurotoxicity caused by BDE-99,and zebrafish embryos model was tested,and thyroid hormone contents,acetylcholinesterase(ache)activity and related of genes expression were examined in zebrafish larvae.Zebrafish embryos/larvae were exposed to BDE-99(0,0.8,4,20,and 100 ?g/L)for 10 days.Reduced survival rates and body length and increased malformation rates were recorded.Increased whole-body tetraiodothyronine(T4)content accompanied by down-regulated corticotropin-releasing hormone(crh)and thyroid-stimulating-hormone subunit beta(tsh?)mRNA levels in larvae were detected.While lowered whole-body triiodothyronine(T3)contents,accompanied by downregulated deio2 mRNA levels were examined.BDE-99 induced neurotoxicity the ache activity was significantly increased,accompanied by down-regulated syn2?,mbp,and shh mRNA levels.Our results showed that zebrafish embryos/larvae exposed to BDE-99 causes thyroid disruption and neurotoxicity and developmental toxicity.2.Although polybrominated diphenyl ethers(PBDEs)are known to disturb thyroid hormone signaling,the mechanisms underlying the effects of 2,2',4,4'5-pentain polybrominated diphenyl ethers(BDE-99)in fish remain unclear.In order to reveal these mechanisms',adult zebrafish(Danio rerio)were exposed to different concentrations of BDE-99(0,0.5,5,or 50 ?g/L)for 28 days and spawn by mating naturally in clean water(without BDE-99).Females exposed to BDE-99 showed significantly lowered thyroxine(T4)levels.Expression of transthyretin(ttr)and uridine diphosphate glucuronosyl transferase(ugt1ab)was down-regulated and up-regulated,respectively.Triiodothyronine(T3)levels in the 0.5 ?g/L BDE-99 exposure group was significantly increased.Males showed significantly increased T3 levels,and lowered T4 levels,which were associated with up-regulated and down-regulated expression of deiodinase 2(deio2)and ugt1 ab,respectively.Exposure of adult zebrafish to BDE-99 lead to significantly increased T4 in the 0.5 ?g/L BDE-99 exposure group,but in the 50 ?g/L BDE-99 exposure group there was significantly reduced T4 in F1 larvae and altered mRNA transcription in the hypothalamic-pituitary-thyroid-liver(HPTL)axis.The offspring also showed reduced survival rates,and body length and elevated malformation rates.This study is the first in zebrafish to show that parental zebrafish exposure to BDE-99 can lead to developmental toxicity and thyroid disruption in the offspring.