Chronic exposure to F-53B disrupts sperm quality and steroidogenic regulation in male rats

Chlorinated polyfluoroalkyl ether sulfonic acid (Cl-PFESAs, trade name F-53B), an emerging substitute for perfluorooctane sulfonates (PFOS) used as mist suppressor in electroplating in China, has raised increasing attention due to its environmental persistence, bioaccumulation, and potential health risks. F-53B exposure has been associated with multi-system toxicities, including hepatotoxicity, immunotoxicity, and developmental toxicity, etc. However, its chronic effects on mammalian reproductive system remain poorly understood. In this study, male Sprague-Dawley (SD) rats were exposed to F-53B via drinking water (0, 1, 10, 100, 1000 μg/L, corresponding to estimated doses of 0, 0.00008, 0.0008, 0.008 and 0.08 mg/kg/day) for 180 days to evaluate its reproductive toxicity. F-53B exposure led to reduced sperm counts, elevated sperm abnormality rates, along with histopathological damage in testicular and epididymal tissues. Hormonal disruptions were evident, including decreased testosterone and follicle-stimulating hormone (FSH) levels as well as increased gonadotropin-releasing hormone (GnRH), indicating hypothalamic-pituitary-testicular (HPT) axis disruption. Additionally, F-53B chronic exposure impaired testicular endocrine function in male SD rats, as reflected by dysregulated hormone receptor expression, reduced enzymatic activity, and inhibited testosterone biosynthesis.These findings demonstrate that chronic exposure to F-53B markedly disrupts sperm quality and steroidogenic regulation in male rats. Given the increasing environmental prevalence of F-53B and bioaccumulative nature of F-53B, the current study highlights a significant concern for its reproductive health risks in mammals and implies an urgent need for comprehensive toxicological evaluation of its widespread use.