Gestational exposure to a fluorotelomer alcohol causes behavioral abnormalities by disrupting the blood–brain barrier in offspring

Abstract

Fluorotelomer alcohols are an alternative to neurotoxic perfluoroalkyl carboxylic acids, a sub-class of per- and poly-fluoroalkyl substances (PFAS). However, the effect of the fluorotelomer alcohol in offspring is poorly known. Here pregnant mice were exposed to various doses of the 6:2 fluorotelomer alcohol through intragastric administration from gestation day 8.5 until delivery. Results show that the fluorotelomer alcohol impaired the development of the blood–brain barrier and altered brain immune microenvironment, causing anxiety-like behavior and impairments in learning memory. Mechanistic studies suggest that this is due to the activation of the serine and threonine kinase AKT/nuclear factor kappa-b/matrix metalloproteinases signaling pathway, resulting in the degradation of the tight junction protein occludin, which in turn caused disruption of endothelial barrier function. Our findings represent the first evidence that gestational exposure to the 6:2 fluorotelomer alcohol causes neurotoxicity in offspring.