Oxygenated Polycyclic Aromatic Hydrocarbons Inducing Developmental Toxicity Of Zebrafish And Its Epigenetics Mechanisms

Oxygenated polycyclic aromatic hydrocarbons(OPAHs)are derivatives of PAHs prevalent in the environment,a kind of persistent organic pollutants.OPAHs have thus been proposed to be ‘ dead-end products ' of many biological and chemical degradation pathways owe to its stability and tendency to accumulation in environment.The toxic effects of PAHs have been the subject of many studies;however,less is known about the toxicity of OPAHs.Zebrafish were used as a model organism to explore development toxicity of OPAHs by acute exposure of both embryos and adult zebrafish in this study.We explained development toxicity from both embryonic and transgenerational toxicity.We also analysis intestinal damage and folic acid concentration in adult zebrafish.In embryo acute exposure,9-FLO exposure reduced total body length,eye length and heart rate,decreased insulin generation,interfered with glucose metabolism,and altered the expression of pancreatic organogenesis-related genes pdx-1,foxa2,isl1 and ptf1 a.In particular,low-dose embryonic 9-FLO exposure significantly decreased ?-cell differentiation marker gene pdx-1 m RNA levels,indicating that pancreatic endocrine is a more sensitive target response to embryonic low-dose OPAH exposure.Additionally,we found that DNA methyltransferases dnmt1 and dnmt3 were elevated and the DNA methylation at promoter regions of pdx-1was increased at an early stage of development.In the acute exposure test of adult zebrafish,OPAHs exposure caused the intestinal damage,decreased expression of TJP2 and Muc2.1 in the exposed group.The expression of aryl hydrocarbon receptor was significantly up-regulated in all zebrafish,while the expression of ER was significantly decreased.After 7 days' exposure of zebrafish pairing for spawning,the parental exposure to 9-FLO resulted in decreased mortality,hatching rate and heart rate,abnormal rate and heart defects of offspring.The supplementation of folic acid remitted the developmental delay and protect the heart development.Overall,low-dose OPAHs restricted the early development of embryos but not enough to kill the zebrafish.The OPAH embryonic exposure can impair pancreatic endocrine development by increasing DNA methylation at the promoter regions of pdx-1 that are essential for ?-cell differentiation.Adult zebrafish exposed to 9-FLO may cause intestinal damage by disrupting the intestinal barrier function,thereby interfering with the normal production of folic acid in gut,resulting in low expression of DNA methylation,which increased risk of colorectal adenomas.The negative effects of parental exposure to 9-FLO on offspring may be greater than that of offspring exposure.The supplementation of folic acid may rescue partly the adverse outcomes caused by parental exposure,especially cardiac development.