Reproductive Toxicity Andgenotoxicity Of 4-bromodiphenyl Ether In Male Mice

Polybrominated diphenyl ethers(PBDEs)are a kind of common flame tetardants and widespread in the environment and the organism as a group of persistent organic pollutants.Epidemiological studies have found that it may have reproductive and developmental toxicity.But its toxic mechanism has not been clarified.Higher brominated diphenyl ethers can degrade in the environment to PBDEs with fewer bromines in the environment.And the latter is more volatile and bio-accumulative.Therefore,low brominated PBDEs may have a greater impact on human health and only a few research focused on it.Research purpose: In order to study the reproductive toxicity and genotoxicity of the low brominated PBDEs,we chose 4-Bromodiphenyl ether(BDE-3),which is the representative low brominated PBDEs,as test article to treat C57 male mice and performed metabolomics analyses for the testis,urine and serum samples after treatment.We tend to provide more evidence to better understand the mechanism of BDE-3-induced toxicity.Methods: Male mice were randomly allocated and treated intragastrically with BDE-3 for consecutive six weeks at different dosages of 0.0015,1.5,10 and 30 mg/kg/day.The mice were anesthetized.The blood samples,urine samples,testis,epididymis were collected.The peripheral blood reticulocyte micronucleus test and Phosphatidylinositol complementation group A(Pig-a)gene mutation test were used to investigate the genotoxicity of BDE-3.The reproductive toxicity was studied by sperm quality parameters and histopathological examination of the testis and epididymis.And using UPLC-Q-TOF/MS to analysis the contour to the testis,blood and urine sample to identify the differential metabolites and the metabolic pathway.Results:The sperm count decreased after the treatment of BDE-3 for 6 weeks at a very low dose(0.0015 mg/kg/day).At and above the dose of 1.5 mg/kg/day,the sperm count decreased with statistical significance.Microscopical changes of germ cell lossinseminiferous tubules and epididymides were clearly observed at the dose of 30 mg/kg/day.Pathway analysis revealed that several pathways were potentially related to BDE-3 induced toxicity including amino acids metabolism,purine metabolism,pentose and glucuronate interconversions,biotin metabolism,oxidative phosphorylation,riboflavin metabolism,and glycerophospholipid metabolism and etc.Conclusion: In this study,we successfully observed the reproductive toxicity induced by BDE-3 in male mice which may be caused by the abnormal metabolic process of the purine,amino acids,micronutrients and lipids.