Photoperiod perturbations impact PFNA induced developmental toxicity [PFNA-5day]

ABSTRACT: Background and Purpose: Perfluoronanoic acid (PFNA) is a synthetic long chain (C  8) homologue of per and polyfluoroalkyl substances (PFAS) which is frequently detected in environment as an emerging contaminant with potential threats to living organisms. It has broad applications in industrial and consumer products including adhesives, water and paint repellent surfaces, non-sticky coatings and lubricants. PFNA is very stable and persistent in the environment due to high energy carbon-fluorine bonds and anti-degradation (photo and microbial) properties. Studies show that PFNA caused immune, cardiac, endocrine, reproductive and developmental toxicity. This study investigates the developmental toxicity of PFNA using behavioral assay especially focus on organ specific toxicity via transcriptomic analysis. Methods: Tropical 5D zebrafish embryos were exposed to different concentrations of PFNA (0, 0.031, 0.31, 3.12, 6.25 and 12.5 M) from 2-hour post fertilization (hpf) to 120 hpf under light/dark (14hr light/10 hr dark) or dark (24 hr dark) conditions in temperature-controlled incubator at 28 C. Larval photomotor response (LPR) was conducted to assess change in behavioral patterns. For organic specific toxicity, embryos were exposed to 0 and 12.5 M of PFNA for120 hpf. Brain and eyes were dissected and extracted RNA was sent to Novogene for sequencing. Gene Ontology (GO) and Kyoto Encyclopedia Genes and Genomes (KEGG) analysis were performed using SR plots. For statistical analysis, Kruskal-Wallis test followed by Dunn’s test was opted for behavior data using GraphPad Prism While R software was used for differential expression analysis. Results: PFNA exposure led to significant behavioral alterations in zebrafish larvae at 6.25 and 12.5 M characterized by hyperactivity during light phases and distinct “O-bend” responses in the LPR assay. This hyperactivity indicates neurotoxic and visual impairments which forced us to focus on transcriptomic analysis of brain and eye. RNA sequencing showed 287 differentially expressed genes (DEGs) in brain while that of 683 in eye. GO and KEGG pathways analysis revealed that the common affected pathways in both organs were circadian rhythms, steroid biosynthesis, fatty acid metabolism and PPAR signaling. Additionally, in brain we noticed disruptions in insulin and notch signaling while in eye P53 signaling and phototransduction were affected. Finally, these results suggest that PFNA affects circadian rhythms/biological clocks and vision by influencing various metabolic and signaling pathways potentially contributing to hyperactivity. Conclusion: This study demonstrates that PFNA exposure disrupts neurodevelopmental processes in zebrafish embryos by impairing circadian rhythm and vision. The findings underscore the neurotoxic potential of PFNA and its ability to interfere with both behavioral and molecular pathways. Collectively, this research highlights the need for environmental and regulatory evaluations of PFNA and other PFAS, focusing on their long-term impacts on neurodevelopment and circadian rhythm and potential health risks in contaminated ecosystems and populations.

ORGANISM(S): Danio rerio

PROVIDER: GSE310406 | GEO | 2026/05/15

REPOSITORIES: GEO