The Thyroid-disrupting Effects Of PFDoA And PFHxA On Zebrafish Larvae

In our research,zebrafish were used as a model organism to explore the two widely used kinds of perfluorination,perfluorinated acid(Perfluorododecanoic twelve acid,PFDoA)and perfluorinated caproic acid(Undecafluorohexanoic Acid,PFHxA)on the endocrine disrupting effects of toxicity and their potential mechanism.We first studied the developmental toxicity and mechanism of PFDoA and PFHxA from the perspective of endocrine disruption,and revealed their effects on the expression of genes and protein within the hypothalamus-pituitary-thyroid axis and thyroid hormone content in zebrafish.Furthermore,the toxic effects of PFDoA and PFHxA on the thyroid system and its mechanism were studied.Finally,from the perspective of developmental toxicity,variations on gene and protein expression and THs level,we further compared the differences and similarities between the long chain PFDoA and the short chain PFHxA on the developmental toxicity and endocrine disrupting effects of zebrafish embryos.The main results are as follows:(1)After fertilization,the zebrafish embryos were exposed to different concentrations of PFDoA(0,0.24,1.2 and 6 mg/L).The results demonstrated that the growth of the zebrafish was inhibited.The body length,heart rate and hatching rate decreased significantly,while the malformation and mortality rate obviously increased after 96 h.Beside,the teratogenicity of the chorda oedema and the chord bending could be found in the zebrafish.The exposure group significantly inhibited the secretion of triiodothyronine(T3)and tetraiodothyronine(T4)levels in the young fish.At the same time,the expressions of gene and protein related to the hypothalamus pituitary thyroid axis(HPT)also changed remarkably.Hence,PFDoA may interfere with the secretion of thyroid hormones by regulating the expression of important genes on the HPT axis,thereby affecting the early development of zebrafish embryos and juveniles.And there is a significant dose-effect relationship for different exposure concentrations.(2)After fertilization,the zebrafish embryos were exposed to different concentrations of PFHxA(0,0.48,2.4 and 12 mg/L).The results showed that the growth of zebrafish was inhibited and the length of body decreased significantly after 96 h.In addition,the teratogenicity of the juvenile fish could be caused by the oedema of the heart cyst and the deformation of the tail.The exposure group significantly inhibited the content of T4 in the young fish,but increasd T3 content.At the same time,the expression genes related to the HPT axis also changed significantly.The present study integrated morphological,biochemical and gene expression analyses that have revealed the endocrine toxicity caused by PFDoA during zebrafish embryo development.Our data suggested that PFHxA exposure resulted in abnormal TH levels,increased percentage of deformities and decreased body length of zebrafish larvae,demonstrating that the thyroid endocrine disturbance induced by PFHxA might lead to growth inhibition in the early stages of zebrafish development.Furthermore,PFHxA modulated the expression of a process of genes involved in the HPT axis,demonstrating the clear endocrine disrupting toxicity.And there is also a significant dose-effect relationship for different exposure concentrations.(3)The results showed that PFDoA had a much more significant effect on the body length and malformation rate of the zebrafish.Hence,the acute toxicity of PFDoA was stronger than that of PFHxA.In addition,during the early development of zebrafish,the upregulations of crh,trh and tshβ,which were regarded as important regulator of HPT axis,is closely related to the secretion of thyroid hormone.Although the role of PFDoA and PFHxA is consistent with these three important regulatory factors,they can still lead to different thyroid hormone levels,and then produce different endocrine disrupting effects in different ways.