As alternatives to traditional per- and polyfluoroalkyl
substances,
perfluoroalkyl phosphonic acids (PFPiAs) are widely present in aquatic
environments and can potentially harm aquatic organisms. Pigmentation
affects the probability of aquatic organisms being preyed on and serves
as an important toxic endpoint of development, but little is known
about the impacts of PFPiAs on the development of aquatic organisms.
In this study, Xenopus laevis embryos
were exposed to 6:6 PFPiA (1, 10, and 100 nM) for 14 days. The developed
tadpoles exhibited evident pigmentation with increased melanin particle
size and density on the skin. Pathological and behavioral experiments
revealed that the retinal layers became thinner, reducing the photosensitivity
and disturbing the circadian rhythm of the tadpoles. Compared to the
control group, the exposed tadpoles showed higher levels but less
changes of melanin throughout the light/dark cycle, as well as distinct
oxidative damage. Consequently, the expression level of microphthalmia-associated
transcription factor (MITF), a key factor inducing melanin synthesis,
increased significantly. Molecular docking analysis suggested that
6:6 PFPiA forms strong interactions in the binding pocket of MITF,
implying that it could activate MITF directly. The activation of MITF
ultimately promotes melanin synthesis, resulting in pigmentation on
tadpoles.