Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP)
As the typical aryl-organophosphate flame retardants (OPFRs), triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to be estrogen disruptors. However, estrogen receptor α (ERα) binding experiments could not explain their biological effects. In this study, their...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651321011817 |
| _version_ | 1818573816897470464 |
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| author | Xiaoya Ji Na Li Mei Ma Xinyan Li Kongrui Zhu Kaifeng Rao Zijian Wang Jingfeng Wang Yanjun Fang |
| author_facet | Xiaoya Ji Na Li Mei Ma Xinyan Li Kongrui Zhu Kaifeng Rao Zijian Wang Jingfeng Wang Yanjun Fang |
| author_sort | Xiaoya Ji |
| collection | DOAJ |
| description | As the typical aryl-organophosphate flame retardants (OPFRs), triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to be estrogen disruptors. However, estrogen receptor α (ERα) binding experiments could not explain their biological effects. In this study, their action on ERα, G protein-coupled estrogen receptor (GPER) and the synthesis of 17β-estradiol (E2) were investigated using in vitro assays and molecular docking. The results showed that TPhP acted as an ERα agonist and recruited steroid receptor co-activator 1 (SRC1) and 3 (SRC3), which was found for the first time. Unlike TPhP, TDCIPP acted as an ERα antagonist. However, both TPhP and TDCIPP activated the estrogen pathway by GPER in SKBR3 cells which were lack of ERα. Although molecular docking results revealed that both TPhP and TDCIPP could dock into ERα and GPER, their substituent groups and combination mode might affect the receptor activation. In addition, by using estrogen biosynthesis assay in H295R cells, both of TPhP and TDCIPP were found to promote E2 synthesis and E2/T ratio involving their different alteration on levels of progesterone, testosterone and estrone, and expression of various key genes. Our data proposed estrogen-disrupting mechanism frameworks of TPhP and TDCIPP. Moreover, our results will contribute to future construction of adverse outcome pathway (AOP) framework of endocrine disruptors. |
| first_indexed | 2024-12-15T00:17:57Z |
| format | Article |
| id | doaj.art-d87cf5a7eb2f40d2b8be89c6f7affa55 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-12-15T00:17:57Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-d87cf5a7eb2f40d2b8be89c6f7affa552022-12-21T22:42:25ZengElsevierEcotoxicology and Environmental Safety0147-65132022-01-01229113069Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP)Xiaoya Ji0Na Li1Mei Ma2Xinyan Li3Kongrui Zhu4Kaifeng Rao5Zijian Wang6Jingfeng Wang7Yanjun Fang8Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; School of Public Health, Qingdao University, Qingdao 266000, ChinaKey Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; Correspondence to: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Haidian District, Beijing 100085, China.Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, China; Correspondence to: Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, 18 Shuangqing Road, Haidian District, Beijing 100085, China.Institute of Environmental and Ecological Engineering, Guangdong University of Technology, Guangzhou 510006, ChinaKey Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; College of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, ChinaKey Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, ChinaCollege of Resources and Environment, University of Chinese Academy of Sciences, Beijing 100049, ChinaTianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin 300050, ChinaTianjin Institute of Environmental and Operational Medicine, Key Laboratory of Risk Assessment and Control for Environment & Food Safety, Tianjin 300050, ChinaAs the typical aryl-organophosphate flame retardants (OPFRs), triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) were reported to be estrogen disruptors. However, estrogen receptor α (ERα) binding experiments could not explain their biological effects. In this study, their action on ERα, G protein-coupled estrogen receptor (GPER) and the synthesis of 17β-estradiol (E2) were investigated using in vitro assays and molecular docking. The results showed that TPhP acted as an ERα agonist and recruited steroid receptor co-activator 1 (SRC1) and 3 (SRC3), which was found for the first time. Unlike TPhP, TDCIPP acted as an ERα antagonist. However, both TPhP and TDCIPP activated the estrogen pathway by GPER in SKBR3 cells which were lack of ERα. Although molecular docking results revealed that both TPhP and TDCIPP could dock into ERα and GPER, their substituent groups and combination mode might affect the receptor activation. In addition, by using estrogen biosynthesis assay in H295R cells, both of TPhP and TDCIPP were found to promote E2 synthesis and E2/T ratio involving their different alteration on levels of progesterone, testosterone and estrone, and expression of various key genes. Our data proposed estrogen-disrupting mechanism frameworks of TPhP and TDCIPP. Moreover, our results will contribute to future construction of adverse outcome pathway (AOP) framework of endocrine disruptors.http://www.sciencedirect.com/science/article/pii/S0147651321011817Triphenyl phosphate (TPhP)Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP)Estrogen disrupting effectsEstrogen receptor α (ERα)G protein-coupled estrogen receptor (GPER)Estrogen biosynthesis |
| spellingShingle | Xiaoya Ji Na Li Mei Ma Xinyan Li Kongrui Zhu Kaifeng Rao Zijian Wang Jingfeng Wang Yanjun Fang Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) Ecotoxicology and Environmental Safety Triphenyl phosphate (TPhP) Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) Estrogen disrupting effects Estrogen receptor α (ERα) G protein-coupled estrogen receptor (GPER) Estrogen biosynthesis |
| title | Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) |
| title_full | Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) |
| title_fullStr | Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) |
| title_full_unstemmed | Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) |
| title_short | Comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate (TPhP) and tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) |
| title_sort | comparison of the mechanisms of estrogen disrupting effects between triphenyl phosphate tphp and tris 1 3 dichloro 2 propyl phosphate tdcipp |
| topic | Triphenyl phosphate (TPhP) Tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) Estrogen disrupting effects Estrogen receptor α (ERα) G protein-coupled estrogen receptor (GPER) Estrogen biosynthesis |
| url | http://www.sciencedirect.com/science/article/pii/S0147651321011817 |
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