Perfluorohexane Sulfonate (PFHxS) Alters the Choroid Plexus Transcriptome and Enters the Developing Rat Brain
On this page:
Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants associated with developmental neurotoxicity. Recently, human biomonitoring showed that PFAS are detectable in newborn cerebrospinal fluid (CSF). This suggests that these chemicals may cross the protective blood-brain and blood-CSF barriers. Thus, understanding how PFAS enter the brain is crucial for determining their risk. To confirm whether PFAS can cross the brain barriers and to delineate a potential mechanism, we exposed pregnant rats to perfluorohexane sulfonate (PFHxS, 50 mg/kg/day) or vehicle control during pregnancy and lactation. PFHxS was chosen as the test compound due to its efficacy in entering human CSF. From the day of birth until postnatal day 14 (PN14), PFHxS was measured in pup sera and in perfused brain on PN6. These data show that PFHxS has significant lactational transfer, and brain PFHxS is ~1/100 of serum. This shows that PFHxS enters the brain but likely not by passive diffusion. Next, we performed RNA-Seq of the PN6 blood-CSF barrier (choroid plexus). We detected 158 differentially expressed genes in PFHxS exposed animals compared with controls (FDR q<0.05). Pathway analyses revealed that PFHxS downregulates endoplasmic reticulum stress and alters expression of carboxylic acid transport. Together, these data suggest that PFHxS cross the brain barriers. Additionally, PFHxS is likely not diffusing into the brain, but may be transported across the brain barriers via endogenous carboxylic acid transporters. As PFHxS and many other PFAS are structurally similar to fatty acids, this mechanism may be biologically plausible. This work does not reflect US EPA policy.