Liver MiRNA Expression Changes In Rat Exposed To PFOS

Perfluorooctane sulfonate(PFOS) is a new type of persistent organic pollutants(POPs), and it is one of the representative compounds of perfluorinated organic compounds (PFCs). Based on good biological recalcitrance, chemical and thermal stability for PFOS, it has been used in multiple industrial and civilian products. With substances including PFOS benefits to the human life, some bad influences happened. Environmental researchers found that these compounds have been detected in the living organisms and human medium of worldwide. In view of the potential threat of PFOS on the human and the whole ecological environment, PFOS has been officially added to the Stockholm Convention on Persistent Organic Pollutants (POPs) in2009.SD rats exposed to PFOS during pregnancy and lactation were used as a model, miRNA arrays were used to identify liver miRNAs expression changes. Bioinformatics and statistics approaches were employed to predict and analyze relative functions and interactions of the significantly changed miRNA for potential target genes, including pathways(PW), molecular function(MF), biological process(BP). The results indicated that PFOS affected the expression of related miRNAs, resulting in potential threat to the corresponding physiological and biochemical processes of the early development of rat pups liver. In addition. They provides the theoretical basis for the further study of the mechanisms of early developmental toxicity of PFOS. The main conclusions are as follows:(1) The effect of embryonic and breast-feeding early exposure to PFOS on miRNA expression in rat liver. Analysis result indicates that387matured miRNAs have been measured in the chip,201were detected in pups liver by using miRNA microarray and Statistical analysis. Kernal density curves showed that PFOS exposure significantly affected the expression of miRNA-density distribution at the first day(PND1) or seventh day(PND7) after births, which indicated that miRNA expression were more sensitive between PNDs1and7in pups liver. Compared with the control group, there are46and9significantly changed micoRNAs on both PND1and PND7respectively, the significantly down-regulated miRNAs were11and1, the significantly up-regulated miRNAs were35and8. Of all the miRNAs, miR-125a-3p, miR-23a*, miR-25and miR-494were down regulated on PND1, while up regulated on PND7.41and5miRNAs become specific expressed at PNDs1and7respectively. The above results suggest early PFOS exposure during embryonic and breast-feeding may affect the expression profile of related miRNAs in the rat pups liver. In additon, bioinformatics analysis for four significant changed miRNAs(miR-125a-3p, miR-23a*, miR-25, miR-494) on both PND1and PND7. Analysis results suggested that PFOS exposure potentially altered the biological process(BP) associated with the neurotransmitter and impulse transmission, synaptic vesicle transport, protein transport, response to endogenous stimulus; the potential molecular function(MF) included passive transmembrane transporter activity, channel activity, protein dimerization activity, solute: cation symporter activity, cytoskeletal protein binding, protein kinase binding; the potential biological pathways(PW) related to cancer pathways, neuroactive ligand receptor interaction, Calcium signaling pathway, long term potentiation. These results indicate that PFOS through these four miRNAs potentially affect the developing nervous system, immune system development, glucose and lipid metabolism and cancer and other life processes.(2) The effects of embryo and early breast-feeding exposure to PFOS on fatty acid metabolism in rat liver. Bioinformatics analysis for significantly changed miRNAs on both PND1and PND7found:Toxic effects of PFOS during the embryonic period was stronger than the early breast-feeding. In the early development of rat pups liver PFOS affected glucose and lipid metabolism and cell apoptotic process. During embryonic and early breast-feeding period, low dose of PFOS exposure also affected β and ω oxidative metabolism involved in liver fatty acid metabolic process. Some key enzyme of fatty acid metabolism like acyl-CoA synthetase, acyl CoA dehydrogenase and enoyl CoA hydrated enzymes, were the potential target molecules of significantly changed miRNAs of PFOS exposure. These results suggest that PFOS has a variety of early liver developmental toxicities. the significantly changed miRNA can regulate the expression of target genes involed in liver fatty acid metabolism at low dose of PFOS(3.2mg/kg Food). In addition, the expression of the key enzyme in fatty acid metabolic process are still in need for further experiments to confirm on toxicity differences between the vivo and vitro experiments at different doses.In this study, we found that PFOS exposure during early development can change expression profile in rat pups liver. Significantly expressed miRNAs can potentially affect the developing nervous system, immune system development, glucose and lipid metabolism, cancer and other life processes. Accordingly, we speculated that PFOS may regulat the toxic process through the induction of related miRNA expression. PFOS can affect miRNA expression related to fatty acid metabolism by entering the cell membrane or nuclear membrane directly, changing the permeability of cell membranes and induce mRNA expression of fatty acid metabolism, or forming a promoter or repressor through binding to the miRNA transcription factors of mRNA upstream. This finding provides the theoretical basis for the further study of the mechanism for PFOS early developmental toxicity. and brings great significance to the health and safety risk assessment.