Qualitative Exploration of Ultrastructural Effects of Perfluorooctanoic Acid on Carp Gills: Mitochondria-Rich Cells as Candidate Biomarkers of Cytotoxicity

Perfluorooctanoic acid (PFOA), a persistent per- and polyfluoroalkyl substance (PFAS), remains a global toxicological concern due to its ubiquity, bioaccumulation potential, and toxicity even at low concentrations. This study aimed to elucidate the ultrastructural effects of PFOA on the gills of Cyprinus carpio, a species of high ecological and trophic relevance. Gill samples from fish experimentally exposed to two PFOA concentrations (200 ng L⁻¹ and 2 mg L⁻¹), one of which was environmentally relevant, were examined by transmission electron microscopy. The results revealed cytotoxic changes primarily affecting mitochondria-rich (chloride) cells and, to a lesser extent, epithelial and mucous cells. The main alterations included mitochondrial degeneration, Golgi and endoplasmic reticulum stress, and autophagic activation, indicating a coordinated impairment of the endomembrane system. These findings suggest that PFOA induces a bioenergetic and proteo-synthetic imbalance compromising cellular homeostasis. Both direct cytotoxic and indirect endocrine-mediated mechanisms may contribute to the observed lesions. The pronounced sensitivity of mitochondria-rich cells supports their use as generalist biomarkers of PFOA exposure and effect. Within a One Health framework, these cells may also serve as translational models for elucidating conserved subcellular mechanisms of PFAS-induced cytotoxicity across vertebrates, with implications for environmental and human health risk assessment.