8:8 Perfluoroalkyl Phosphinic Acid Affects Neurobehavioral Development, Thyroid Disruption, and DNA Methylation in Developing Zebrafish
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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.
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Exposure of zebrafish larvae to ≥0.343 μM of 8:8 perfluoroalkyl phosphinic acid (8:8 PFPiA) resulted in decreased overall distance traveled.
“Exposure of zebrafish larvae to ≥0.343 µM of 8:8 perfluoroalkyl phosphinic acid (8:8 PFPiA) similarly resulted in decreased overall distance traveled.”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Kim et al., 2020
5.79 μM 8:8 PFPiA caused a concurrent decrease in locomotor speed during a light-to-dark transition in zebrafish larvae.
“However, in contrast to other compounds, 5.79 µM 8:8 PFPiA caused a concurrent decrease in locomotor speed during a light-to-dark transition (Kim et al., 2020).”
From A Critical Review and Meta-Analysis of Impacts of Per- and Polyfluorinated Substances on the Brain and Behavior (2022) · cites this paper as Kim et al., 2020
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- Authors
- Kim, S., Stroski, K. M., Killeen, G., Smitherman, C., Simcik, M. F., & Brooks, B. W.
- Affiliations
- Baylor University (US)
- Baylor Scott & White Research Institute (US)
- University of Minnesota (US)
- Corresponding author
- Brooks, Bryan W.
- Venue
- Science of The Total Environment
- Publisher
- Elsevier BV
- Published
- 2020-09
- Volume
- 736
- Pages
- 139600
- ISSN
- 0048-9697 (ISSN-L)
- OpenAlex
- W3031057806
- Cited by
- 66
- References
- 59
- Citations by year
- 2026: 6 · 2025: 16 · 2024: 12 · 2023: 14 · 2022: 7 · 2021: 8 · 2020: 3
- FWCI
- 2.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The Science of The Total Environment (acceptedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Strategic Environmental Research and Development Program
- Topics
- Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Toxic Organic Pollutants Impact
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- per- and polyfluoroalkyl substances, brain development, neurobehavioral development, locomotion speed, thyroid hormone signaling, DNA methylation, epigenetic regulation, oxidative stress, elavl3, DIO3, TSHR, TTF-1, zebrafish embryo toxicity, developmental toxicity
- MeSH terms
- Animals, Fluorocarbons, Phosphinic Acids, Thyroid Gland, Zebrafish, DNA Methylation, Epigenesis, Genetic
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