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题名: Mechanistic study of chlordecone-induced endocrine disruption: Based on an adverse outcome pathway network
作者: Yang, Lihua; Zhou, Bingsheng; Zha, Jinmiao; Wang, Zijian
刊名: CHEMOSPHERE
出版日期: 2016-10
卷号: 161, 期号:0, 页码:372-381
关键词: Chlordecone ; Chinese rare minnow (Gobiocypris rams) ; Endocrine disruption ; Adverse outcome pathway (AOP)
DOI: 10.1016/j.chemosphere.2016.07.034
部门归属: 中国科学院饮用水科学与技术重点实验室
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.
收录类别: SCI
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内容类型: 期刊论文
URI标识: http://ir.rcees.ac.cn/handle/311016/36198
Appears in Collections:中国科学院饮用水科学与技术重点实验室_期刊论文

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Recommended Citation:
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(0):372-381.
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