Immunotoxicity And Mechanism Of Action Of The Endocrine Disrupting Chemicals Bisphenol S And Bisphenol F In Zebrafish During Early Developmental Stages

Bisphenol A(BPA)has been recognized as an endocrine disrupting chemical which can simulate the estrogenic effects of endogenous estrogens.Bisphenol A has a wide range of environmental distribution,mainly because BPA belongs to one of the mostly used industrial raw materials.It is mainly used in the synthesis of precursors of polycarbonate,epoxy resin,plasticizer,etc.As much of industrial sewage disperses into the water body,BPA can be detected in the common water environment including water,silt and sediment in rivers or lakes.A lot of plastic raw materials which contain BPA can be found in our daily life,including some of the most common ones like baby bottles and all kinds of baby products.BPA attracts broad attention for its toxic potential and the fact that bisphenol A has been widespread in the environment.To find an approach that both the economic benefit results from BPA and environmental quality can be guaranteed,bisphenol S(BPS)and bisphenol F(BPF),regarded as safe substitutes for BPA,are presented.These two kinds of chemicls have similar chemical structures as BPA and have been considered as ideal substitutes for BPA widely implied in inductrusty.The thesis mainly aims to evaluate the feasibility of BPS and BPF as safe substitues for BPA in the industrial production to avoid adverse impacts on creatures in the environment.Using zebrafish embryos and larvae as models,a short term exposure experiments were performed during the every early developmental stages of zebrafish embryos to environmentally relavant concentrations of BPS and BPF.The growth,oxidative stress and immune related indicators were examined to evaluate the toxicity of BPS and BPF.The main results are as follows:(1)A 120 hpf short-term exposure of zebrafish embryos was performed under the concentrations of BPS and BPF at 0.1,1,10,100,1000 ?g/L.The impacts on growth of zebrafish larvae during the early developmental stages were as follows: Compared to the control group,the short-term exposure of 120 hpf resulted in the early hatching time of zebrafish embryos.In the high concentration exposure group,the body length of zebrafish larvae was significantly inhibited.(2)The impacst of BPS and BPF exposure on the antioxidant system in zebrafish larvae during the early developmental stages were as follows: The relatively high concentrations of chemical exposure significantly increased reactive oxygen species(ROS)content and the activities of oxidative stress parameters.The high concentration exposure significantly induced the NO content in vivo and enhanced the activity of induce nitric oxide synthase and total nitric oxide synthase,which would affect the antioxidant system function in zebrafish larvae.(3)The impacts of BPS and BPF exposure on the expression of immune related genes in zebrafish's during the early developmental stages were as follows: The expression levels of genes interleukin-1,interleukin-6,interleukin-10,interleukin-11,interleukin-12,Tumour necrosis factor-?,CC-chemokine,Interferon ? in zebrafish larvae were significantly increased under high concentration chemical exposure,similar to the immune toxicity of BPA.(4)In addition,the BPS and BPF exposure induced the expression of estrogen receptor ?(ER?)and the nuclear factor-?B(NF-?B)in zebrafish larvae.However,the coexposure of BPS and BPF with addition of the inhibitors of er? and NF-?B significantly restrained the induction of expression of immune related genes IL-1b,IL-6,TNF-a,IFNg caused by BPS and BPF exposure,indicating that the ER? and NF-?B signalling pathways play important roles in mediating the actions of BPS and BPF on fish immune response and functions,similar to the effects and mechanism of action of BPA.In conclusion,our results revealed that a short term exposure to BPS and BPF during the very early developmental stages could signicantly affect the growth,oxidant defense system and immune ralted parameters in zebrafish larvae.Therefore,BPS and BPF are not absolutrely safer substitues for BPA,and these two chemicals should not be widely used without any restriction and protection measures.