Time-course transcriptome analysis discloses PFDMO2OA (C8 HFPO-TA)-induced developmental malformations and cardiovascular toxicities in zebrafish

PFDMO2OA (C8 HFPO-TA), a novel substitute for perfluorooctanoic acid (PFOA), has been frequently detected in surface waters. However, information on its toxicity remains scarce. In the present study, zebrafish embryos were exposed to varying concentrations of PFDMO2OA, ranging from 80 to 800 mg/L, until 120 h post-fertilization (hpf) to explore its potential developmental toxicities. The LC50 value for mortality was 505.9 mg/L, comparable to that of PFOA (over 500 mg/L), suggesting a lack of safety of PFDMO2OA compared to PFOA. At 120 hpf, PFDMO2OA exposure led to various malformations in embryos, including uninflated swim bladder, yolk sac oedema, spinal deformation, and pigmentation changes, with pericardial oedema being prominent. Analysis using O-dianisidine stain indicated a decline in erythrocytes over time. Transcriptome analysis further revealed the cardiovascular toxicity caused by PFDMO2OA at the molecular level. Time-course differential analysis pointed to the apoptosis dependent on disrupted mitochondrial function as a significant contributor to erythrocyte disappearance, as confirmed by the TUNEL stain. Therefore, the present findings suggest that PFDMO2OA induces developmental malformations and cardiovascular toxicities in zebrafish embryos, demonstrating a toxic potency comparable to that of PFOA. The results further highlight the significance of evaluating the health risks associated with PFDMO2OA.