Perfluorooctanesulfonamide-induced epiboly delay is associated with decreased ATP production within zebrafish embryos.

Per- and polyfluoroalkyl substances (PFAS) persistence within environmental media has led to ubiquitous exposure within humans and wildlife. We previously found that exposure of zebrafish embryos to perfluorooctanesulfonamide (PFOSA) from 0.75 to 6 h post-fertilization (hpf) resulted in a concentration-dependent delay in epiboly - a critical developmental landmark in fish and amphibian species. Therefore, for this study, we explored whether 1) similar mechanisms underlie epiboly delays induced by PFOSA or Cytochalasin B (CCB), a potent inhibitor of actin polymerization that disrupts normal epiboly progression, and 2) PFOSA-induced epiboly delay is associated with a decrease in embryonic ATP, as PFOSA is a potent uncoupler of oxidative phosphorylation in vitro. Although PFOSA and CCB induced a similar magnitude of epiboly delay beginning at 4 hpf following initiation of exposure at 0.75 hpf, PFOSA did not, contrary to CCB, significantly decrease yolk-associated actin within embryos. Using mRNA-sequencing, we also found that, consistent with chemical-specific differences in effects on actin polymerization, PFOSA-exposed embryos were also transcriptionally different from CCB-exposed embryos. Moreover, phenotypically matched, PFOSA-exposed embryos at 6 hpf were transcriptionally similar to vehicle-exposed embryos at 5 hpf, and PFOSA delayed the maternal-to-zygotic transition (MZT) beginning at 5 hpf. Finally, PFOSA-induced delayed epiboly was associated with decreased ATP concentrations, an effect that was partially mitigated by co-exposure to exogenous ATP. Overall, our findings suggest that PFOSA exposure during early embryonic development decreases ATP production in the absence of effects on actin polymerization in vivo, an effect that is associated with PFOSA-induced delays in epiboly and the MZT.