Dose-Dependent Effects of PFOS on Thyroid Hormone-Driven Neurodevelopment and Metamorphic-like change in Xenopus laevis larvae

Abstract

PFOS is a banned stain repellent that is a type of PFAS, a category of chemicals commonly referred to as "forever chemicals." These substances are known for their bioaccumulative nature and their resistance to degradation in the environment. Emerging data indicates that PFOS may disrupt thyroid hormone (TH) signaling, which plays a pivotal role in healthy vertebrate development, particularly neural development. Our study investigates whether PFOS interferes with TH-dependent developmental changes, with focus on the developing brain, in Xenopus laevis larvae. To assess this, we exposed five-day old larvae to varying concentrations of PFOS (25 g/L, 2.5 g/L, and 250 ng/L). Additionally, some larvae were exposed to either 15 g/L or 1.5 g/L of thyroxine to evaluate PFOSs potential interference with TH-dependent developmental mechanisms. After four days, we euthanized larvae and examined body length and hind limb size, dissected out brains and performed immunostaining for markers of neuronal proliferation and apoptosis. We found that PFOS significantly impeded overall body growth in a dose-dependent manner, irrespective of TH status. Moreover, PFOS impaired TH-stimulated hind limb development. In the brain, PFOS had no effect on proliferation but hindered TH-stimulated growth of the optic tectum. Last, PFOS increased apoptosis in the optic tectum, indicative of cytotoxicity. These findings suggest that PFOS may have the capacity to disrupt TH-dependent mechanisms involved in brain development. The observed pattern of change also suggests that its impact is cytotoxic and may not stem solely from a canonical endocrine disruption mechanism.