Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network

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	Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network
	Yang, Lihua 1; Zhou, Bingsheng 1; Zha, Jinmiao 2,3; Wang, Zijian 4
刊名	CHEMOSPHERE
	2016-10-01
卷号	161 页码:372-381
关键词	Chlordecone Chinese rare minnow (Gobiocypris rams) Endocrine disruption Adverse outcome pathway (AOP)
ISSN号	0045-6535
英文摘要	The adverse outcome pathway (AOP) framework could be helpful for chemical risk assessment and mechanistic research. The aim of the present study was to unravel the mechanism of chlordecone-induced endocrine disruption by illustrating the main molecular initiating event (MIE)/perturbations responsible for the observed effects. In silico simulations were performed to predict the MIE(s), and the results pointed to agonistic interaction with estrogen receptors (ER alpha, ER beta), androgen receptor (AR), cytochrome P450 (CYP19A) by chlordecone. In vivo endocrine disruptions were evaluated in rare minnow (Gobiocypris rarus) exposed to 0.01, 0.1, 1 and 10 mu g L-1 chlordecone from 2 h post-fertilization until sexually mature. In the females, increases of vitellogenin (vtg) mRNA levels in liver and gonad, plasma estradiol (E2), testosterone (T) and E2/T, and renalsomatic index confirmed the role of agonism of ER and CYP19A as MIEs, but the decreased gonadosomatic index, degenerated ovaries as well as the feed forward response pointed to other potential but important MIEs and corresponding AOPs. In the males, increased E2/T ratio, increased testis vtg mRNA levels and occurrence of intersex confirmed the roles of agonism of ERa and CYP19A as main MIEs in chlordecone-induced endocrine disruptions. Our results also fetches out the limit of AOPs in predicting the adverse outcomes and explaining the mechanism of chemicals at present, thus reflected a critical need for expanding AOPs and AOP network before using it in chemical risk assessment. (C) 2016 Published by Elsevier Ltd.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Environmental Sciences
研究领域[WOS]	Environmental Sciences & Ecology
关键词[WOS]	MEDAKA ORYZIAS-LATIPES ; MINNOW PIMEPHALES-PROMELAS ; GENE-EXPRESSION ; GOBIOCYPRIS-RARUS ; DMRT1 EXPRESSION ; RISK-ASSESSMENT ; DANIO-RERIO ; BISPHENOL-A ; TESTIS-OVA ; RECEPTOR
收录类别	SCI
语种	英语
WOS记录号	WOS:000382409200045
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/28376]
专题	水生生物研究所_淡水生态学研究中心_学位论文
作者单位	1.Chinese Acad Sci, Inst Hydrobiol, State Key Lab Freshwater Ecol & Biotechnol, Wuhan 430072, Peoples R China 2.Chinese Acad Sci, Ecoenvironm Sci Res Ctr, State Key Lab Drinking Water Sci & Technol, POB 2871,Shuangqing Rd 18, Beijing 100085, Peoples R China 3.Chinese Acad Sci, Ecoenvironm Sci Res Ctr, Beijing Key Lab Ind Wastewater Treatment & Reuse, Beijing 100085, Peoples R China 4.Chinese Acad Sci, Ecoenvironm Sci Res Ctr, State Key Lab Environm Aquat Chem, POB 2871, Beijing 100085, Peoples R China
推荐引用方式 GB/T 7714	Yang, Lihua,Zhou, Bingsheng,Zha, Jinmiao,et al. Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network[J]. CHEMOSPHERE,2016,161:372-381.
APA	Yang, Lihua,Zhou, Bingsheng,Zha, Jinmiao,&Wang, Zijian.(2016).Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network.CHEMOSPHERE,161,372-381.
MLA	Yang, Lihua,et al."Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network".CHEMOSPHERE 161(2016):372-381.