Insight into the mechanisms of neuroendocrine toxicity induced by 6:2FTCA via thyroid hormone disruption

• Published in: Chemosphere (Oxford) 2023-11, Vol.341, p.140031-140031, Article 140031
• Main Authors: Wu, Linlin, Gu, Jie, Duan, Xinjie, Ge, Feng, Ye, Heyong, Kong, Lingcan, Liu, Wenwei, Gao, Rong, Jiao, Jiandong, Chen, Huanhuan, Ji, Guixiang
• Format: Article
• Language: English
• Subjects: 6:2 FTCA; carboxylic acids; Danio rerio; endocrine-disrupting chemicals; energy; Neuroendocrine toxicity; neurotransmitters; perfluorooctanoic acid; public health; risk; therapeutics; Thyroid hormone disruption; thyroid hormone receptors; thyroid hormones; toxicity; tryptophan; tyrosine; Zebrafish
• ISSN: 0045-6535; 1879-1298
• DOI: 10.1016/j.chemosphere.2023.140031

6:2 fluorotonic carboxylic acid (6:2 FTCA), a novel substitute for perfluorooctanoic acid (PFOA), is being used gradually in industrial production such as coatings or processing aids, and its detection rate in the aqueous environment is increasing year by year, posing a potential safety risk to aquatic systems and public health. However, limited information is available on the effects and mechanism of 6:2 FTCA. Therefore, this study was conducted to understand better the neuroendocrine effects of early exposure to 6:2 FTCA and the underlying mechanisms on zebrafish. In this study, zebrafish embryos were treated to varied doses of 6:2 FTCA (0, 0.08 μg/mL, 0.8 μg/mL and 8 μg/mL) at 4 h post-fertilization (hpf) for a duration of six days, which exhibited a pronounced inhibition of early growth and induced a disorganized swim pattern characterized by reduced total swim distance and average swim speed. Simultaneously, the thyroid development of zebrafish larvae was partially hindered, accompanied by decreased T3 levels, altered genes associated with the expression of thyroid hormone synthesis, transformation and transportation and neurotransmitters associated with tryptophan and tyrosine metabolic pathways. Molecular docking results showed that 6:2 FTCA has a robust binding energy with the thyroid hormone receptor (TRβ). Moreover, exogenous T3 supplementation can partially restore the adverse outcomes. Our findings indicated that 6:2 FTCA acts as a thyroid endocrine disruptor and can induce neuroendocrine toxic effects. Furthermore, our results show that targeting TRβ may be a potentially therapeutic strategy for 6:2 FTCA-induced neuroendocrine disrupting effects. [Display omitted] •6:2 FTCA exposure affected zebrafish development.•6:2 FTCA exposure caused abnormalities in thyroid function and motor neuron development in zebrafish.•Thyroid development is impaired in zebrafish larvae and partially restored by exogenous T3 supplementation.•The molecular docking and rescue assays indicated that TRβ could be the potential targets of 6:2 FTCA induced neuroendocrine disrupting effects.