Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid (PFOA), has been widely used and ubiquitously detected in aquatic environments. However, its potential effects on sex differentiation of aquatic organisms are not well known. Therefore, in this study, zebrafish were exposed to HFPO-TA at different development stages (0-21, 21-42, and 42-63 dpf) to investigate the effects on sex differentiation and its underlying mechanisms. All three exposures to HFPO-TA resulted in the feminization of zebrafish, and the impact of Stage II was most significant. The transcription levels of key genes related to female differentiation (bpm15, cyp19a1a, esr1, vtg1, and sox9b) were up-regulated, while those of key genes related to male differentiation (dmrt1, gata4, amh, and sox9a) were down-regulated, which could lead to the feminization. In addition, it was found that the dysregulations of these genes were prolonged in adult zebrafish even through a long recovery, which could cause sex imbalance in populations. Therefore, HFPO-TA might not be a safe alternative to PFOA, and more evidences from multi- and transgenerational toxicology are warranted.
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