Novel Insights on 6:6 Perfluoroalkyl Phosphonic Acid-Induced Melanin Synthesis Disorders Leading to Pigmentation in Tadpoles

Abstract

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.

Underlying Mechanisms for the Sex- and Chemical-Specific Hepatotoxicity of Perfluoroalkyl Phosphinic Acids in Common Carp (Cyprinus carpio)

“…Common carp (25.4 ± 3.3 g wet weight) used for the experiments were purchased from a local aquarium (Tianjin, China) and allowed to acclimate in the laboratory for 2 weeks before exposure. Two exposure concentrations of 20 and 200 nM for both 6:6 and 8:8 PFPiAs (i.e., 14.5 and 145 μg/L for 6:6 PFPiA and 18.5 and 185 μg/L for 8:8 PFPiA) were tested in this study based on the toxicity threshold (LC 50 of 96 h zebrafish test is between 10 and 100 mg/L) and previous investigations. − Details about the stock solution preparation and fish exposure procedures according to OECD Test Guideline 305 are provided in Text S2. The measured concentrations of 6:6 and 8:8 PFPiAs in the exposure solutions were very close to the nominal concentrations (20 and 200 nM) and remained stable during the exposure period (Table S2).…”