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

Kaifeng Rao¹  Xinyan Li²  Zijian Wang²  Na Li³  Jingfeng Wang⁴  Kongrui Zhu⁵  Mei Ma⁵  Xiaoya Ji⁵  Yanjun Fang⁵ 

[1] 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.;School of Public Health, Qingdao University, Qingdao 266000, China;Institute of Environmental and Ecological Engineering, Guangdong University of Technology, Guangzhou 510006, China;Key Laboratory of Drinking Water Science and Technology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China;

关键词: 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;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown