Cited by 41Epigenetics and DNA MethylationEffects and risks of endocrine disrupting chemicalsCarcinogens and Genotoxicity Assessment

Gene expression of epigenetic regulatory factors related to primary silencing mechanism is less susceptible to lower doses of bisphenol A in embryonic hypothalamic cells

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Warita, Katsuhiko, Mitsuhashi, Tomoko, Ohta, Ken-ichi, Suzuki, Shingo, Hoshi, Nobuhiko, Miki, Takanori, Takeuchi, Yoshiki·2013·The Journal of Toxicological Sciences

Abstract

DNA methyltransferases (DNMTs) are associated with epigenetic regulation of gene expression, and methyl-CpG binding protein 2 (MECP2) acts as a long-range regulator of methylated genes. We evaluated the effects of bisphenol A (BPA) on embryonic mouse hypothalamic cells, with particular emphasis on the gene expression of Dnmts (Dnmt1, Dnmt3a, and Dnmt3b) and Mecp2 isoforms. In a dose-dependent (0.02-200 µM BPA) 3-hr experiment, real-time reverse transcription polymerase chain reaction revealed that gene expression of both Dnmts and Mecp2_e2 was affected at 200 µM and that of Mecp2_e1 was affected at > 20 µM. These results suggest that gene expression of Dnmts and Mecp2 are less susceptible to lower doses of BPA in developing hypothalamic cells. However, as BPA concentration increases, this agent has the potential to alter gene expression of key players that provide stability and flexibility of epigenetic gene regulation, which could disrupt the normal development of hypothalamic functions.

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Authors
Warita, K., Mitsuhashi, T., Ohta, K.-I., Suzuki, S., Hoshi, N., Miki, T., & Takeuchi, Y.
Affiliations
  • University of Pittsburgh (US)
  • Kagawa University (JP)
  • Kobe University (JP)
Venue
The Journal of Toxicological Sciences
Published
2013
Volume
38
Issue
2
Pages
285-289
ISSN
  • 0388-1350 (ISSN-L)
  • 1880-3989
OpenAlex
W2030088208
Cited by
41
References
21
Citations by year
2026: 1 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 1 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 1
FWCI
2.39
Type
journal article
Language
en
Open access
Locations
  • The Journal of Toxicological Sciences (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science and Technology
  • Japan Society for the Promotion of Science (21791037)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
Keywords
bisphenol A, DNA methyltransferases, DNMT1, DNMT3A, DNMT3B, MeCP2, epigenetic regulation, DNA methylation, dose-dependent effects, endocrine disruptors, hypothalamic development
MeSH terms
DNA (Cytosine-5-)-Methyltransferase 1, DNA Methyltransferase 3A, DNA Methyltransferase 3B, Bisphenol A Compounds, Animals, Benzhydryl Compounds, Cells, Cultured, DNA (Cytosine-5-)-Methyltransferases, Dose-Response Relationship, Drug, Hypothalamus, Phenols, RNA, Gene Expression, DNA Methylation, Protein Isoforms, Epigenesis, Genetic, Mice, Methyl-CpG-Binding Protein 2, Real-Time Polymerase Chain Reaction

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