Metabolomics Coupled with Pathway Analysis Characterizes Metabolic Changes in Response to BDE-3 Induced Reproductive Toxicity in Mice

Overview

Journal Sci Rep

Specialty Science

Date 2018 Apr 5

PMID 29615664

Citations 12

Authors

Ziheng Wei

Jing Xi

Songyan Gao

Xinyue You

Na Li

Yiyi Cao

Liupeng Wang

Yang Luan

Xin Dong

Affiliations

Soon will be listed here.

Abstract

Polybrominated diphenyl ethers (PBDEs) may affect male reproductive function. 4-bromodiphenyl ether (BDE-3), the photodegradation products of higher brominated PBDEs, is the most fundamental mono-BDE in environment but is less studied. The purpose of this study was to investigate the reproductive toxicity induced by BDE-3 and explore the mechanism by metabolomics approach. In this study, mice were treated intragastrically with BDE-3 for consecutive six weeks at the dosages of 0.0015, 1.5, 10 and 30 mg/kg. The reproductive toxicity was evaluated by sperm analysis and histopathology examinations. UPLC-Q-TOF/MS was applied to profile the metabolites of testis tissue, urine and serum samples in the control and BDE-3 treated mice. Results showed the sperm count was dose-dependently decreased and percentage of abnormal sperms increased by the treatment of BDE-3. Histopathology examination also revealed changes in seminiferous tubules and epididymides in BDE-3 treated mice. Metabolomics analysis revealed that different BDE-3 groups showed metabolic disturbances to varying degrees. We identified 76, 38 and 31 differential metabolites in testis tissue, urine and serum respectively. Pathway analysis revealed several pathways including Tyrosine metabolism, Purine metabolism and Riboflavin metabolism, which may give a possible explanation for the toxic mechanism of BDE-3. This study indicates that UHPLC-Q-TOFMS-based metabolomics approach provided a better understanding of PBDEs-induced toxicity dynamically.

Citing Articles

Teratogenicity, cardiac toxicity, neurotoxicity and genotoxicity in zebrafish embryo-larvae exposed to 4-bromodiphenyl ether.

Kumar S, Chadha P Toxicol Res (Camb). 2025; 14(1):tfae228.

PMID: 39781281 PMC: 11705087. DOI: 10.1093/toxres/tfae228.

Investigation of Metabolic and Inflammatory Disorder in the Aging FGF21 Knockout Mouse.

Cai L, Li X, Wang Y, Chen Y, Zhu X, Zuo Z Inflammation. 2024; 47(6):2173-2195.

PMID: 38653921 PMC: 11607023. DOI: 10.1007/s10753-024-02032-3.

Update of the risk assessment of polybrominated diphenyl ethers (PBDEs) in food.

Schrenk D, Bignami M, Bodin L, Chipman J, Del Mazo J, Grasl-Kraupp B EFSA J. 2024; 22(1):e8497.

PMID: 38269035 PMC: 10807361. DOI: 10.2903/j.efsa.2024.8497.

Streamlined identification of strain engineering targets for bioprocess improvement using metabolic pathway enrichment analysis.

Cortada-Garcia J, Daly R, Arnold S, Burgess K Sci Rep. 2023; 13(1):12990.

PMID: 37563133 PMC: 10415327. DOI: 10.1038/s41598-023-39661-x.

Recent Review on Selected Xenobiotics and Their Impacts on Gut Microbiome and Metabolome.

Jin Y, Chi J, LoMonaco K, Boon A, Gu H Trends Analyt Chem. 2023; 166.

PMID: 37484879 PMC: 10361410. DOI: 10.1016/j.trac.2023.117155.

References

Akutsu K, Takatori S, Nozawa S, Yoshiike M, Nakazawa H, Hayakawa K . Polybrominated diphenyl ethers in human serum and sperm quality. Bull Environ Contam Toxicol. 2008; 80(4):345-50. DOI: 10.1007/s00128-008-9370-4. View

Gao S, Yang R, Peng Z, Lu H, Li N, Ding J . Metabolomics analysis for hydroxy-L-proline-induced calcium oxalate nephrolithiasis in rats based on ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry. Sci Rep. 2016; 6:30142. PMC: 4957101. DOI: 10.1038/srep30142. View

Lu C, Wang Y, Sheng Z, Liu G, Fu Z, Zhao J . NMR-based metabonomic analysis of the hepatotoxicity induced by combined exposure to PCBs and TCDD in rats. Toxicol Appl Pharmacol. 2010; 248(3):178-84. DOI: 10.1016/j.taap.2010.07.020. View

Zhuang Y, Ahn S, Luthy R . Debromination of polybrominated diphenyl ethers by nanoscale zerovalent iron: pathways, kinetics, and reactivity. Environ Sci Technol. 2010; 44(21):8236-42. PMC: 2969174. DOI: 10.1021/es101601s. View

Wang Y, Shi J, Li L, Liu D, Li L, Tang C . Adverse effects of 2,2',4,4'-tetrabromodiphenyl ether on semen quality and spermatogenesis in male mice. Bull Environ Contam Toxicol. 2012; 90(1):51-4. DOI: 10.1007/s00128-012-0867-5. View

Helleday T, Tuominen K, Bergman A, Jenssen D . Brominated flame retardants induce intragenic recombination in mammalian cells. Mutat Res. 1999; 439(2):137-47. DOI: 10.1016/s1383-5718(98)00186-7. View

Kanehisa M, Goto S . KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res. 1999; 28(1):27-30. PMC: 102409. DOI: 10.1093/nar/28.1.27. View

Naughton C, Nangia A, Agarwal A . Pathophysiology of varicoceles in male infertility. Hum Reprod Update. 2001; 7(5):473-81. DOI: 10.1093/humupd/7.5.473. View

Selle H, Chapman B, Kuchel P . Glycerophosphocholine release in human erythrocytes. 1H spin-echo and 31P-NMR evidence for lysophospholipase. Eur J Biochem. 1993; 212(2):411-6. DOI: 10.1111/j.1432-1033.1993.tb17676.x. View

10.

Ji C, Wu H, Wei L, Zhao J, Yu J . Proteomic and metabolomic analysis reveal gender-specific responses of mussel Mytilus galloprovincialis to 2,2',4,4'-tetrabromodiphenyl ether (BDE 47). Aquat Toxicol. 2013; 140-141:449-57. DOI: 10.1016/j.aquatox.2013.07.009. View

11.

Nakata H . A1 adenosine receptor of rat testis membranes. Purification and partial characterization. J Biol Chem. 1990; 265(2):671-7. View

12.

Nagato E, Simpson A, Simpson M . Metabolomics reveals energetic impairments in Daphnia magna exposed to diazinon, malathion and bisphenol-A. Aquat Toxicol. 2015; 170:175-186. DOI: 10.1016/j.aquatox.2015.11.023. View

13.

Horvath C, DRUGA A . Action of the phenothiazine derivative methophenazine on prenatal development in rats. Teratology. 1975; 11(3):325-9. DOI: 10.1002/tera.1420110312. View

14.

Lawton L, Donaldson W . Lead-induced tissue fatty acid alterations and lipid peroxidation. Biol Trace Elem Res. 1991; 28(2):83-97. DOI: 10.1007/BF02863075. View

15.

Zhang Z, Zhang X, Sun Z, Dong H, Qiu L, Gu J . Cytochrome P450 3A1 mediates 2,2',4,4'-tetrabromodiphenyl ether-induced reduction of spermatogenesis in adult rats. PLoS One. 2013; 8(6):e66301. PMC: 3676375. DOI: 10.1371/journal.pone.0066301. View

16.

Eguchi A, Miyaso H, Mori C . The effects of early postnatal exposure to a low dose of decabromodiphenyl ether (BDE-209) on serum metabolites in male mice. J Toxicol Sci. 2016; 41(5):667-75. DOI: 10.2131/jts.41.667. View

17.

Kato R, Maeda T, Akaike T, Tamai I . Characterization of novel Na+-dependent nucleobase transport systems at the blood-testis barrier. Am J Physiol Endocrinol Metab. 2005; 290(5):E968-75. DOI: 10.1152/ajpendo.00160.2005. View

18.

Zhang J, Shen H, Xu W, Xia Y, Barr D, Mu X . Urinary metabolomics revealed arsenic internal dose-related metabolic alterations: a proof-of-concept study in a Chinese male cohort. Environ Sci Technol. 2014; 48(20):12265-74. PMC: 4204897. DOI: 10.1021/es503659w. View

19.

Facciotti F, Ramanjaneyulu G, Lepore M, Sansano S, Cavallari M, Kistowska M . Peroxisome-derived lipids are self antigens that stimulate invariant natural killer T cells in the thymus. Nat Immunol. 2012; 13(5):474-80. DOI: 10.1038/ni.2245. View

20.

You X, Xi J, Cao Y, Zhang J, Luan Y . 4-Bromodiphenyl Ether Induces Germ Cell Apoptosis by Induction of ROS and DNA Damage in Caenorhabditis elegans. Toxicol Sci. 2017; 157(2):510-518. DOI: 10.1093/toxsci/kfx064. View