Chronic Perfluorooctanoic Acid Exposure in Young Adult Zebrafish Affects Scale and Internal Skeleton Bone Metabolism, as Well as Offspring Bone Development

Perfluorooctanoic acid (PFOA) is one of the most extensively investigated per- and polyfluoroalkyl substances (PFAS), a class of highly fluorinated organic compounds widely used in consumer products. While assessing the long-term health effects of chronic PFOA exposure in humans remains challenging, simple animal models like zebrafish serve as essential tools to identify potential toxicological risks. The aim of this study was to investigate the chronic effects of PFOA on bone metabolism in young adult zebrafish, as well as the potential transgenerational impacts on their offspring. Fish fed a PFOA-enriched diet exhibited a significant decrease in body weight and length compared to the untreated control group. Explanted scales, which accumulated PFOA within the mineralized matrix, showed a reduced surface area, impaired osteoblastic activity, and strong osteoclastic activity localized in the central region of the scale. Furthermore, endoskeletal analysis revealed a series of malformations across multiple sites, including the vertebrae, ribs, fins, operculum, and branchial arches. The viability and general development of embryos derived from PFOA-treated parents showed no significant variations compared to controls, despite accumulating PFOA. Nevertheless, osteogenesis was specifically inhibited in the trunk of these PFOA-exposed embryos. Overall, this study highlights not only early perturbations in bone remodeling but also the transgenerational impact of PFOA on skeletal development in the offspring.