Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice

A representative congener of polybrominated diphenyl ethers in the environment, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), is associated with male reproductive toxicity, yet the underlying mechanisms remain largely unclear. In this study, mice were administered environmentally relevant concentrati...

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Autores principales: Xu, Liang, Gao, Songyan, Zhao, Hongxia, Wang, Liupeng, Cao, Yiyi, Xi, Jing, Zhang, Xinyu, Dong, Xin, Luan, Yang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229108/
https://www.ncbi.nlm.nih.gov/pubmed/34072909
http://dx.doi.org/10.3390/biom11060821
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author Xu, Liang
Gao, Songyan
Zhao, Hongxia
Wang, Liupeng
Cao, Yiyi
Xi, Jing
Zhang, Xinyu
Dong, Xin
Luan, Yang
author_facet Xu, Liang
Gao, Songyan
Zhao, Hongxia
Wang, Liupeng
Cao, Yiyi
Xi, Jing
Zhang, Xinyu
Dong, Xin
Luan, Yang
author_sort Xu, Liang
collection PubMed
description A representative congener of polybrominated diphenyl ethers in the environment, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), is associated with male reproductive toxicity, yet the underlying mechanisms remain largely unclear. In this study, mice were administered environmentally relevant concentrations of BDE-47 for six weeks. Histopathological observations showed that BDE-47 induced inflammatory reactions and damaged the testes. By conducting an integrated proteomic and metabolomic analysis coupled with a bioinformatic analysis using ingenuity pathway analysis (IPA) methods, we found that BDE-47 mainly affected the molecules involved in free radical scavenging, cell death and survival, neurological disease, and inflammatory response. IPA canonical pathways showed inflammatory and apoptosis pathways, including hepatic fibrosis/hepatic stellate cell activation, the GP6 signaling pathway, tight junction signaling, acute phase response signaling, LXR/RXR activation, unfolded protein response, and FXR/RXR activation, which are related to male reproductive toxicity. Key transcriptional regulator networks were activated via a focus on upstream regulator analysis. The expression of MYC and Clu as the core transcriptional factor and targeted protein, respectively, was verified. It is further proposed that MYC may contribute to the etiology of male reproductive toxicity. These findings will improve our understanding of the mechanisms responsible for BDE-47-induced male reproductive toxicity, which may promote the discovery of useful biomarkers indicative of BDE-47 exposure.
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spelling pubmed-82291082021-06-26 Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice Xu, Liang Gao, Songyan Zhao, Hongxia Wang, Liupeng Cao, Yiyi Xi, Jing Zhang, Xinyu Dong, Xin Luan, Yang Biomolecules Article A representative congener of polybrominated diphenyl ethers in the environment, 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47), is associated with male reproductive toxicity, yet the underlying mechanisms remain largely unclear. In this study, mice were administered environmentally relevant concentrations of BDE-47 for six weeks. Histopathological observations showed that BDE-47 induced inflammatory reactions and damaged the testes. By conducting an integrated proteomic and metabolomic analysis coupled with a bioinformatic analysis using ingenuity pathway analysis (IPA) methods, we found that BDE-47 mainly affected the molecules involved in free radical scavenging, cell death and survival, neurological disease, and inflammatory response. IPA canonical pathways showed inflammatory and apoptosis pathways, including hepatic fibrosis/hepatic stellate cell activation, the GP6 signaling pathway, tight junction signaling, acute phase response signaling, LXR/RXR activation, unfolded protein response, and FXR/RXR activation, which are related to male reproductive toxicity. Key transcriptional regulator networks were activated via a focus on upstream regulator analysis. The expression of MYC and Clu as the core transcriptional factor and targeted protein, respectively, was verified. It is further proposed that MYC may contribute to the etiology of male reproductive toxicity. These findings will improve our understanding of the mechanisms responsible for BDE-47-induced male reproductive toxicity, which may promote the discovery of useful biomarkers indicative of BDE-47 exposure. MDPI 2021-05-31 /pmc/articles/PMC8229108/ /pubmed/34072909 http://dx.doi.org/10.3390/biom11060821 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Xu, Liang
Gao, Songyan
Zhao, Hongxia
Wang, Liupeng
Cao, Yiyi
Xi, Jing
Zhang, Xinyu
Dong, Xin
Luan, Yang
Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice
title Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice
title_full Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice
title_fullStr Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice
title_full_unstemmed Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice
title_short Integrated Proteomic and Metabolomic Analysis of the Testes Characterizes BDE-47-Induced Reproductive Toxicity in Mice
title_sort integrated proteomic and metabolomic analysis of the testes characterizes bde-47-induced reproductive toxicity in mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229108/
https://www.ncbi.nlm.nih.gov/pubmed/34072909
http://dx.doi.org/10.3390/biom11060821
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