TY - JOUR
T1 - Fluroxypyr-1-methylheptyl ester interferes with the normal embryogenesis of zebrafish by inducing apoptosis, inflammation, and neurovascular toxicity
AU - An, Garam
AU - Park, Hahyun
AU - Lim, Whasun
AU - Song, Gwonhwa
N1 - Funding Information:
This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Ministry of Science and ICT (MSIT) (grant numbers: 2021R1A2C2005841 and 2021R1C1C1009807 ).
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/9
Y1 - 2021/9
N2 - Fluroxypyr-1-methylheptyl ester (FPMH) is a synthetic auxin herbicide used to regulate the growth of post-emergence broad-leaved weeds. Although acute exposure to FPMH increases the mortality of several fish species in the juvenile stage, the developmental toxicity of FPMH in aquatic vertebrates has not yet been investigated. In the present study, we assessed the developmental toxicity of FPMH using zebrafish models that offer many advantages for studying toxicology. During embryogenesis, survival rates gradually decreased with increasing FPMH concentrations and exposure times. At 120 h post-fertilization, FPMH-exposed zebrafish larvae showed various abnormalities such as small eye size, heart defects, enlarged yolk sac, and shortened body length. The study results confirmed the induction of apoptosis in the anterior body of zebrafish and upregulation of inflammatory gene expression. Further, defects in vascular networks, especially the loss of central arteries and abnormal aortic arch structures, were seen in the fli1:eGFP transgenic zebrafish model. Neurotoxicity of FPMH was examined using mbp:eGFP zebrafish and which displayed compromised myelination following FPMH administration. Our study has demonstrated the mechanisms underlying FPMH toxicity in developing zebrafish that is a representative model of vertebrates.
AB - Fluroxypyr-1-methylheptyl ester (FPMH) is a synthetic auxin herbicide used to regulate the growth of post-emergence broad-leaved weeds. Although acute exposure to FPMH increases the mortality of several fish species in the juvenile stage, the developmental toxicity of FPMH in aquatic vertebrates has not yet been investigated. In the present study, we assessed the developmental toxicity of FPMH using zebrafish models that offer many advantages for studying toxicology. During embryogenesis, survival rates gradually decreased with increasing FPMH concentrations and exposure times. At 120 h post-fertilization, FPMH-exposed zebrafish larvae showed various abnormalities such as small eye size, heart defects, enlarged yolk sac, and shortened body length. The study results confirmed the induction of apoptosis in the anterior body of zebrafish and upregulation of inflammatory gene expression. Further, defects in vascular networks, especially the loss of central arteries and abnormal aortic arch structures, were seen in the fli1:eGFP transgenic zebrafish model. Neurotoxicity of FPMH was examined using mbp:eGFP zebrafish and which displayed compromised myelination following FPMH administration. Our study has demonstrated the mechanisms underlying FPMH toxicity in developing zebrafish that is a representative model of vertebrates.
KW - Angiogenesis
KW - Embryo development
KW - Fluroxypyr-1-methylheptyl ester
KW - Neurotoxicity
KW - Zebrafish model
UR - http://www.scopus.com/inward/record.url?scp=85104913390&partnerID=8YFLogxK
U2 - 10.1016/j.cbpc.2021.109069
DO - 10.1016/j.cbpc.2021.109069
M3 - Article
C2 - 33930526
AN - SCOPUS:85104913390
SN - 1532-0456
VL - 247
JO - Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
JF - Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
M1 - 109069
ER -