Bisphenol A-associated epigenomic changes in prepubescent girls: A cross-sectional study in Gharbiah, Egypt

Jung H. Kim, Laura S. Rozek, Amr S. Soliman, Maureen A. Sartor, Ahmed Hablas, Ibrahim A. Seifeldin, Justin A. Colacino, Caren Weinhouse, Muna S. Nahar, Dana C. Dolinoy

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Background: There is now compelling evidence that epigenetic modifications link adult disease susceptibility to environmental exposures during specific life stages, including pre-pubertal development. Animal studies indicate that bisphenol A (BPA), the monomer used in epoxy resins and polycarbonate plastics, may impact health through epigenetic mechanisms, and epidemiological data associate BPA levels with metabolic disorders, behavior changes, and reproductive effects. Thus, we conducted an environmental epidemiology study of BPA exposure and CpG methylation in pre-adolescent girls from Gharbiah, Egypt hypothesizing that methylation profiles exhibit exposure-dependent trends. Methods. Urinary concentrations of total (free plus conjugated) species of BPA in spot samples were quantified for 60 girls aged 10 to 13. Genome-wide CpG methylation was concurrently measured in bisulfite-converted saliva DNA using the Infinium HumanMethylation27 BeadChip (N = 46). CpG sites from four candidate genes were validated via quantitative bisulfite pyrosequencing. Results: CpG methylation varied widely among girls, and higher urinary BPA concentrations were generally associated with less genomic methylation. Based on pathway analyses, genes exhibiting reduced methylation with increasing urinary BPA were involved in immune function, transport activity, metabolism, and caspase activity. In particular, hypomethylation of CpG targets on chromosome X was associated with higher urinary BPA. Using the Comparative Toxicogenomics Database, we identified a number of candidate genes in our sample that previously have been associated with BPA-related expression change. Conclusions: These data indicate that BPA may affect human health through specific epigenomic modification of genes in relevant pathways. Thus, epigenetic epidemiology holds promise for the identification of biomarkers from previous exposures and the development of epigenetic-based diagnostic strategies.

Original languageEnglish (US)
Article number33
JournalEnvironmental Health: A Global Access Science Source
Volume12
Issue number1
DOIs
StatePublished - May 21 2013

Fingerprint

Egypt
Epigenomics
Cross-Sectional Studies
Methylation
Genes
Epidemiology
Toxicogenetics
Epoxy Resins
bisphenol A
Reproductive Behavior
Disease Susceptibility
Environmental Exposure
Health
X Chromosome
Caspases
Saliva
Biomarkers
Genome
Databases
DNA

Keywords

  • Bead array
  • Bisphenol A
  • DNA methylation
  • Egypt
  • Epigenetics

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Health, Toxicology and Mutagenesis

Cite this

Bisphenol A-associated epigenomic changes in prepubescent girls : A cross-sectional study in Gharbiah, Egypt. / Kim, Jung H.; Rozek, Laura S.; Soliman, Amr S.; Sartor, Maureen A.; Hablas, Ahmed; Seifeldin, Ibrahim A.; Colacino, Justin A.; Weinhouse, Caren; Nahar, Muna S.; Dolinoy, Dana C.

In: Environmental Health: A Global Access Science Source, Vol. 12, No. 1, 33, 21.05.2013.

Research output: Contribution to journalArticle

Kim, JH, Rozek, LS, Soliman, AS, Sartor, MA, Hablas, A, Seifeldin, IA, Colacino, JA, Weinhouse, C, Nahar, MS & Dolinoy, DC 2013, 'Bisphenol A-associated epigenomic changes in prepubescent girls: A cross-sectional study in Gharbiah, Egypt', Environmental Health: A Global Access Science Source, vol. 12, no. 1, 33. https://doi.org/10.1186/1476-069X-12-33
Kim, Jung H. ; Rozek, Laura S. ; Soliman, Amr S. ; Sartor, Maureen A. ; Hablas, Ahmed ; Seifeldin, Ibrahim A. ; Colacino, Justin A. ; Weinhouse, Caren ; Nahar, Muna S. ; Dolinoy, Dana C. / Bisphenol A-associated epigenomic changes in prepubescent girls : A cross-sectional study in Gharbiah, Egypt. In: Environmental Health: A Global Access Science Source. 2013 ; Vol. 12, No. 1.
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abstract = "Background: There is now compelling evidence that epigenetic modifications link adult disease susceptibility to environmental exposures during specific life stages, including pre-pubertal development. Animal studies indicate that bisphenol A (BPA), the monomer used in epoxy resins and polycarbonate plastics, may impact health through epigenetic mechanisms, and epidemiological data associate BPA levels with metabolic disorders, behavior changes, and reproductive effects. Thus, we conducted an environmental epidemiology study of BPA exposure and CpG methylation in pre-adolescent girls from Gharbiah, Egypt hypothesizing that methylation profiles exhibit exposure-dependent trends. Methods. Urinary concentrations of total (free plus conjugated) species of BPA in spot samples were quantified for 60 girls aged 10 to 13. Genome-wide CpG methylation was concurrently measured in bisulfite-converted saliva DNA using the Infinium HumanMethylation27 BeadChip (N = 46). CpG sites from four candidate genes were validated via quantitative bisulfite pyrosequencing. Results: CpG methylation varied widely among girls, and higher urinary BPA concentrations were generally associated with less genomic methylation. Based on pathway analyses, genes exhibiting reduced methylation with increasing urinary BPA were involved in immune function, transport activity, metabolism, and caspase activity. In particular, hypomethylation of CpG targets on chromosome X was associated with higher urinary BPA. Using the Comparative Toxicogenomics Database, we identified a number of candidate genes in our sample that previously have been associated with BPA-related expression change. Conclusions: These data indicate that BPA may affect human health through specific epigenomic modification of genes in relevant pathways. Thus, epigenetic epidemiology holds promise for the identification of biomarkers from previous exposures and the development of epigenetic-based diagnostic strategies.",
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AU - Rozek, Laura S.

AU - Soliman, Amr S.

AU - Sartor, Maureen A.

AU - Hablas, Ahmed

AU - Seifeldin, Ibrahim A.

AU - Colacino, Justin A.

AU - Weinhouse, Caren

AU - Nahar, Muna S.

AU - Dolinoy, Dana C.

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