The novel PFOS substitute OBS induces visual developmental toxicity in zebrafish embryos via ferroptosis

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS), a widely used substitute for perfluorooctanesulfonic acid, may threaten ocular development, but its mechanisms remain unclear. In this study, zebrafish embryos were exposed to OBS (0, 0.01, 0.1, 1 mg/L) for 120 h. OBS exposure resulted in pronounced ocular developmental abnormalities, including lens deformation, reduced retinal layer thickness, and a significant decrease in eye size. Mechanistic analyses revealed that OBS induced oxidative stress and ferroptosis-associated alterations: the number of early apoptotic cells increased in a dose-dependent manner, accompanied by marked downregulation of key eye development genes (lhx4, pax6, rx1, and vsx1). Additionally, elevated Fe^2 + and malondialdehyde levels, abnormally increased superoxide dismutase activity, and reduced catalase activity and glutathione content were observed. Expression levels of ferroptosis-related genes (gpx4, slc7a11, fth, and tfr) were also significantly altered. Notably, treatment with the ferroptosis-specific inhibitor Ferrostatin-1 (Fer-1) effectively alleviated OBS-induced ocular damage, further supporting ferroptosis as a central regulatory mechanism. Collectively, this study provides the first evidence that ferroptosis plays a pivotal role in OBS-induced ocular developmental defects in zebrafish embryos, offering insights into PFOS alternatives' risks and therapeutic targets.