Binding specificities of estrogen receptor with perfluorinated compounds: A cross species comparison

Background: Perfluorinated compounds (PFCs) were reported to result in the endocrine disruption by activating the estrogen receptor (ER) and inducing ER-mediated transcriptions. Objective: The aim of the present work was to perform cross-species comparisons on the characteristics of eight PFCs binding to humans ER alpha and to rats ER alpha. Methods: In the present work, in vivo tests, including serum estradiol level assay and immunohistochemical staining, fluorescence assay and molecular models were applied. Results: Based on the in vivo experiments, the exposure of PFOA and PFOS to female rats was proved to increase the ER alpha expression in the terus, suggesting that PFCs may act as estrogenic compounds to activate ER alpha in vivo. The further fluorescence assay presented that these eight PFCs have stronger binding abilities to human ER alpha than to rat ER alpha. In addition, the differences in binding specificities between human ER alpha and rat ER alpha were identified in the process of molecular dynamics modeling with the term of helix position and the ability of coregulator recruitment. It can be found that more and stronger charge clamps could form between PFCs with human ER alpha than with rat ER alpha. Also, the eight PFCs presented lower binding energies in human ER alpha systems, which proved that eight PFCs presented much stronger binding abilities with human ER alpha. Discussion: In all, it can be concluded that PFCs might be more sensitive to human ER alpha than to that of rats, which also suggested the greater susceptibility to adverse effects on humans. The present work was a beginning assessment of a cross-species comparison, providing important information on health impacts of PFCs in humans.