Transcriptomic Analysis Based Toxic Effects Of Lanthanides On Zebrafish

With the exploration of the functions of rare earth elements,more and more types and doses of rare earth elements enter the market.Continued exploitation and utilization is increasing the spread of lanthanides from mines to the ecological environment.The surface runoff and infiltration of mining wastewater,the disposal of commodities,and the discharge of industrial sewage lead to the entry of lanthanide elements into the atmosphere,hydrosphere and biosphere.The exposure risk of lanthanide elements in ecological environment increases,which threatens life and health.In recent years,the negative effects of lanthanides have been increasingly reported.The hazards of rare earth elements on organisms is attracting our attention with its increasing background concentration levels in the living environment.However,due to different exposure methods,different studied species,different measured toxicological endpoints,and lack of data,the available studies is insufficient to elucidate the toxic effects,mechanisms,and whether there exists toxicity commonality across lanthanides.In addition,the conventional toxicological tests are generally based on growth inhibition,oxidative stress,embryo aberration,and lethality,which can only give a limited picture of toxicity characteristics.Traditional methods are generally not sensitive enough to distinguish the differences in molecular expression levels between analogues and need high exposure concentrations as well as a long exposure time.Transcriptome analysis has been increasingly applied to the risk assessment of pollutants because of its high efficiency in exploring the toxicity mechanisms of pollutants at the molecular level and distinguishing the toxicity differences between chemical analogues.In addition,transcriptome methods can systematically analyze the response of an organism to external stress at the overall level.In this study,we conducted the acute toxicity test and transcriptome analysis of zebrafish following exposure to La(Ⅲ),Ce(Ⅲ),and Nd(Ⅲ).The acute toxicity tests and response of DEGs showed that the three lanthanides had great similarities as regards the toxic patterns across the three lanthanides.The lethality of the three lanthanides were all at the micro-molar level.Differently expressed genes and functional group network enrichment analysis indicated that the three lanthanides might affect the reproductive system of zebrafish by interfering with some key biomolecules such as steroid,cyclin B and cyclin-dependent kinase(cdk1).Both Ce and Nd also altered gene expression of insulin-like growth factor(igf1),an important molecule in oocyte meiosis.Nd uniquely affects the expression of genes involved in piRNA metabolism process.They also exerted significant effect on the metabolism of xenobiotics through affecting a lot of enzymes(gstp1,alsh3b1)in the four phases of endo-or xenobiotics metabolism process.Some basic biological processes,such as DNA replication,cell cycle,and the p53 signaling pathway are also significantly enriched.In addition,Ce may uniquely perturbed the chemokine-mediated signaling pathway.This work illustrated the toxicity characteristics and modes of action of lanthanum,cerium and neodymium,compared the toxicity order and mode of action of the three elements,which facilitated the ecological and environmental risk assessment of lanthanides.The analytical methods of combining multiple transcriptomic analyses adopted here are worthy of reference in comparing the toxicity patterns between analogs.