Original scientific paper

https://doi.org/10.2478/aiht-2021-72-3555

Epigenetic toxicity and cytotoxicity of perfluorooctanoic acid and its effects on gene expression in embryonic mouse hypothalamus cells

Hun Kim ; Kangwon National University College of Animal Life Sciences, Chuncheon, Korea
Min-Wook Hong ; Kangwon National University College of Animal Life Sciences, Chuncheon, Korea
Yun-ho Bae ; Kangwon National University College of Animal Life Sciences, Chuncheon, Korea
Sung-Jin Lee ; Kangwon National University College of Animal Life Sciences, Chuncheon, Korea

Abstract

Even though the endocrine-disrupting potential of perfluorooctanoic acid (PFOA) is well known, the mechanisms underlying its cellular and epigenetic toxicity at the critical stage of hypothalamic development are poorly understood. This is why we studied its effects on the embryonic mouse hypothalamic cell line N46 (mHypoE-N46) with a hope to shed more light on the mechanisms through which PFOA causes embryonic hypothalamic cell damage. To do that, we studied cell viability, global DNA methylation, and gene expression in cells exposed to PFOA. As the PFOA dose increased, cell viability decreased, while global DNA methylation increased. PFOA also significantly altered the expression of genes related to the apoptosis and cell cycle, neurotrophic genes, and the Tet, Dnmt, and Mecp2 genes. Our findings suggest that exposure to PFOA affects cell survival through the reprogramming of embryonic hypothalamic DNA methylation patterns and altering cell homeostasis genes. DNA methylation and changes in the Mecp2 gene expression induced by PFOA also imply wider ramifications, as they alter genes of other major mechanisms of the embryonic hypothalamus. Our study may therefore serve as a good starting point for further research into the mechanisms of PFOA effect of hypothalamic development.

Keywords

cytotoxicity; DNA methylation; endocrine-disrupting chemicals; epigenetic toxicity; mHypoE-N46 cell line; PFOA

Hrčak ID:

262384

URI

https://hrcak.srce.hr/262384

Publication date:

17.9.2021.

Article data in other languages: croatian

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