PFAS compounds PFOA and Gen X are teratogenic to sea urchin embryos
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Abstract
Per-and polyfluorinated substances (PFAS) are synthetic chemicals that are used to make fluoropolymer coatings found in many products, such as non-stick pans, clothing, cosmetics, and food packaging. These highly persistent molecules are known as “forever chemicals,” since they neither degrade environmentally nor break down enzymatically within biological systems. PFAS compounds easily contaminate water sources, and as a result, PFAS molecules have bioaccumulated in all species including humans. The purpose of this study was to define the effect of two PFAS molecules, the more toxic perfluorooctanoic acid (PFOA) and the more recent, reportedly safer chemical hexafluoropropylene oxide dimer acid (Gen X) in Lytechinus variegatus embryos. We examined the effects of PFOA and Gen X on development and patterning using morphological analysis, immunostaining, and HCR-FISH. We find that both PFOA and Gen X are sufficient to perturb skeletal patterning and primary mesenchyme cell (PMC) migration in L. variegatus embryos, although at relatively high doses, likely reflecting the hydrophilic nature of PFAS compounds that limits their diffusive entry into cells. We find that zygotes are sensitive to PFOA at a lower dose than Gen X. We defined the temporal window of action for both agents by performing timed additions and removals of the chemicals. These results indicate that Gen X is functionally effective between 7 and 13 hpf (hours post-fertilization), which correspond with hatching and mesenchyme blastula stages. In contrast, PFOA is most effective between 21 and 36 hpf, which correspond to prism and early pluteus stages. Both chemicals mildly perturbed ciliary band restriction, as well as expression of Chordin and IxA, which are dorsal-ventral (DV) marker genes. In addition, both chemicals perturbed some PMC subset genes and ectodermal patterning cues, to varying degrees of severity. Together, these data show that PFAS compounds are teratogenic to sea urchin embryos and that PFOA and Gen X provoke distinct outcomes and function at different intervals during development. Though Gen X is thought to be a “safer” alternative to other PFAS like PFOA, our findings indicate that Gen X has an earlier and more severe effect on DV specification, albeit at a higher dose. However, because these chemicals are so stable and persistent in the environment and within biological systems, they will continue to accumulate and their concentrations will continue to increase if strategies to remediate them are not activated, even if their production were to cease. Thus, determining their effects on biological systems at relatively high doses is ecologically relevant; seeking methods for their removal is crucial for the prevention of widespread teratogenesis both environmentally and among humans.