Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation

Rima Woods, Roxanne O. Vallero, Mari S. Golub, Joanne K. Suarez, Tram Anh Ta, Dag H. Yasui, Lai Har Chi, Paul J. Kostyniak, Isaac N Pessah, Robert F Berman, Janine M LaSalle

Research output: Contribution to journalArticle

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Abstract

The widespread use of persistent organic polybrominated diphenyl ethers (PBDEs) as commercial flame retardants has raised concern about potential long-lived effects on human health. Epigenetic mechanisms, such as DNA methylation, are responsive to environmental influences and have long-lasting consequences. Autism spectrum disorders (ASDs) have complex neurodevelopmental origins whereby both genetic and environmental factors are implicated. Rett syndrome is an X-linked ASD caused by mutations in the epigenetic factor methyl-CpG binding protein 2 (MECP2). In this study, an Mecp2 truncation mutant mouse (Mecp2308) with social behavioral defects was used to explore the long-lasting effects of PBDE exposure in a genetically and epigenetically susceptible model. Mecp2308/+ dams were perinatally exposed daily to 2,2',4,4'-tetrabromodiphenyl ether 47 (BDE-47) and bred to wild-type C57BL/6J males, and the offspring of each sex and genotype were examined for developmental, behavioral and epigenetic outcomes. Perinatal BDE-47 exposure negatively impacted fertility of Mecp2308/+ dams and preweaning weights of females. Global hypomethylation of adult brain DNA was observed specifically in female offspring perinatally exposed to BDE-47 and it coincided with reduced sociability in a genotype-independent manner. A reversing interaction of Mecp2 genotype on BDE-47 exposure was observed in a short-term memory test of social novelty that corresponded to increased Dnmt3a levels specifically in BDE-47-exposed Mecp2308/+ offspring. In contrast, learning and long-term memory in the Morris water maze was impaired by BDE-47 exposure in female Mecp2308/+ offspring. These results demonstrate that a genetic and environmental interaction relevant to social and cognitive behaviors shows sexual dimorphism, epigenetic dysregulation, compensatory molecular mechanisms and specific behavioral deficits.

Original languageEnglish (US)
Article numberdds046
Pages (from-to)2399-2411
Number of pages13
JournalHuman Molecular Genetics
Volume21
Issue number11
DOIs
StatePublished - Jun 2012

Fingerprint

Halogenated Diphenyl Ethers
Epigenomics
Mutation
Genotype
Methyl-CpG-Binding Protein 2
Flame Retardants
Rett Syndrome
Long-Term Memory
DNA Methylation
2,2',4,4'-tetrabromodiphenyl ether
Short-Term Memory
Sex Characteristics
Fertility
Learning
Weights and Measures
Water
DNA
Health
Brain

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Woods, R., Vallero, R. O., Golub, M. S., Suarez, J. K., Ta, T. A., Yasui, D. H., ... LaSalle, J. M. (2012). Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Human Molecular Genetics, 21(11), 2399-2411. [dds046]. https://doi.org/10.1093/hmg/dds046

Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. / Woods, Rima; Vallero, Roxanne O.; Golub, Mari S.; Suarez, Joanne K.; Ta, Tram Anh; Yasui, Dag H.; Chi, Lai Har; Kostyniak, Paul J.; Pessah, Isaac N; Berman, Robert F; LaSalle, Janine M.

In: Human Molecular Genetics, Vol. 21, No. 11, dds046, 06.2012, p. 2399-2411.

Research output: Contribution to journalArticle

Woods, R, Vallero, RO, Golub, MS, Suarez, JK, Ta, TA, Yasui, DH, Chi, LH, Kostyniak, PJ, Pessah, IN, Berman, RF & LaSalle, JM 2012, 'Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation', Human Molecular Genetics, vol. 21, no. 11, dds046, pp. 2399-2411. https://doi.org/10.1093/hmg/dds046
Woods R, Vallero RO, Golub MS, Suarez JK, Ta TA, Yasui DH et al. Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. Human Molecular Genetics. 2012 Jun;21(11):2399-2411. dds046. https://doi.org/10.1093/hmg/dds046
Woods, Rima ; Vallero, Roxanne O. ; Golub, Mari S. ; Suarez, Joanne K. ; Ta, Tram Anh ; Yasui, Dag H. ; Chi, Lai Har ; Kostyniak, Paul J. ; Pessah, Isaac N ; Berman, Robert F ; LaSalle, Janine M. / Long-lived epigenetic interactions between perinatal PBDE exposure and Mecp2308 mutation. In: Human Molecular Genetics. 2012 ; Vol. 21, No. 11. pp. 2399-2411.
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