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 <i>Cyprinus carpio</i>, 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.