Toxic Effects Of Phthalates On Development And Glucose Metabolism In Zebrafish

Phthalates?Phthalate Esters,PAEs?belong to a class of chemicals that are extensively used as additives in the production of plastic,paints,lubricants and personal care products.In past years,its ubiquitous presence in the environment and deleterious health effects have drawn serious attention among the scientific community.Therefore,this study was aimed to evaluate the acute developmental toxicity,and the disturbance of glucose metabolism pathways including type 2 diabetes mellitus?T2DM?,after exposure to six priority PAEs using various zebrafish(mc3r^-/-,mc4r^-/-and AB-wild type)embryos.A novel alcian blue-alizarin red double staining was performed to determine the skeletal deformities,which was further confirmed with qRT-PCR.Among all chemicals,DBP,BBP and DEP showed significant developmental abnormalities in zebrafish larvae,including mortality,the inhibition of voluntary movement,and increased heart rate.Moreover,DBP and BBP also affected bone development even at low doses.After exposure to DBP and BBP,the significant down-regulation of sp7 and runx2b genes also showed the confirmation of the staining results.The homozygotes of mc3r^-/-and mc4r^-/-knockout zebrafish showed no phenotype of T2DM without treatment.However,after exposure to PAEs,it was found that both mc3r^-/-and mc4r^-/-zebrafish can be used as high-glucose metabolism-sensitive animal models for water monitoring.Besides,mc4r^-/-zebrafish was more sensitive to environmental pollution than mc3r^-/-zebrafish for glucose metabolism pathways.Compared to the knock-out fish,AB-wild type zebrafish also revealed the risk of glucose metabolism disorder after exposure to PAEs,particularly the high concentration of DEHP and DBP.In 200 mg/L DEHP and 0.05 mg/L DBP groups,AB-wild type adult zebrafish were not affected,while mc4r^-/-zebrafish showed significant T2DM symptoms,indicating that DEHP and DBP had a high risk of T2DM to the hypersensitive people.In short,PAEs can disrupt the normal growth and development of zebrafish and potentially lead to the risk of type2 diabetes.Therefore,the regulative authorities should take strict measures regarding PAEs pollution in the aquatic ecosystem.