In vitro and in vivo Estrogenic Effects of Fluorotelomer Alcohols in Medaka (Oryzias latipes)

The present study demonstrates the estrogenic effects of two fluorotelomer alcohols, such as 1H,1H,2H,2H-perfluorooctan-1-ol (6:2 FTOH) and 1H,1H,2H,2H-perfluorodecan-1-ol (8:2 FTOH), in medaka (Oryzias latipes). An in vitro yeast two-hybrid assay indicated a significant, dosedependent interaction between medaka estrogen receptor α (ERα) and coactivator TIF2 upon treatment with 6:2 FTOH or 8:2 FTOH. In contrast, no interaction with the ERα was observed upon treatment with perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorododecanoic acid (PFDA) or perfluoroundecanoic acid (PFUnDA). Expression analysis of hepatic vitellogenin (VTG) protein showed estrogenic potentials with, 6:2 FTOH and 8:2 FTOH, indicative of the induction of VTG synthesis in the livers of male medaka. We also investigated mRNA expression levels of two ER subtypes and two VTGs in the livers of male medaka following exposure to FTOHs. Quantitative real-time PCR analyses revealed that hepatic ERα, VTG I, and VTG II mRNA responded rapidly to FTOHs such as 6:2 FTOH and 8:2 FTOH after 8-h exposure, whereas no effects of these compounds on ERβ mRNA transcription were observed. These results strongly suggest that certain FTOHs, such as 6:2 FTOH and 8:2 FTOH, induce hepatic VTG through activation of ERα in male medaka.