PUBLICATION

8:8 Perfluoroalkyl phosphinic acid affects neurobehavioral development, thyroid disruption, and DNA methylation in developing zebrafish

Authors
Kim, S., Stroski, K.M., Killeen, G., Smitherman, C., Simcik, M.F., Brooks, B.W.
ID
ZDB-PUB-200601-15
Date
2020
Source
The Science of the total environment   736: 139600 (Journal)
Registered Authors
Keywords
Behavior, Epigenetics, Neurodevelopment, Per- and polyfluoroalkyl substances (PFASs), Perfluoroalkyl phosphinic acids (PFPiA), Thyroid disruption
MeSH Terms
  • Animals
  • DNA Methylation
  • Epigenesis, Genetic
  • Fluorocarbons*
  • Phosphinic Acids
  • Thyroid Gland
  • Zebrafish*
PubMed
32474277 Full text @ Sci. Total Environ.
Abstract
Recent studies have reported potential neurotoxicity and epigenetic alteration associated with exposure to several per- and polyfluoroalkyl substances (PFASs). However, such information is limited to a few compounds (e.g., perfluorooctane sulfonate), primarily based on rodent experiments, and the underlying toxicological mechanism(s) for many PFAS in the environment remain poorly understood. In the present study, we investigated 8:8 perfluoroalkyl phosphinic acid (8:8 PFPiA), an under-studied PFAS with high persistency in the environment and biota, using the zebrafish model. We exposed zebrafish embryos (<4 hpf) to various concentrations of 8:8 PFPiA (0, 0.0116, 0.112, 0.343, 1.34, 5.79 μM) for 144 h. Although there was no significant change in survival, hatchability and malformations, zebrafish locomotor speed at 120 h significantly decreased in dark photoperiod. At 144 h, several genes related to thyroid hormones that are essential for neurodevelopment, including corticotropin releasing hormone b (crhb), iodothyronine deiodinase 3a (dio3a), thyroid-stimulating hormone receptor (tshr) and nkx2 homeobox1 (nkx 2.1), were up-regulated by 8:8 PFPiA at 5.79 μM. 8:8 PFPiA also significantly down-regulated a neurodevelopmental gene, elav like neuron-specific RNA binding protein (elavl3), at 1.34 and 5.79 μM; in addition, one oxidative stress gene was slightly but significantly up-regulated. Further, global DNA methylation was significantly decreased at higher treatment levels, identifying effects of 8:8 PFPiA on epigenetic regulation. However, promoter DNA methylation of selected genes (dio3, tshr, nkx2.1) were not statistically altered, though dio3 methylation showed a decreasing trend with 8:8 PFPiA exposure. Our results specifically advance an understanding of molecular toxicology of PFPiA and more broadly present an approach to define diverse responses during animal alternative assessments of PFASs.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping