Bisphenol a exposure is associated with in vivo estrogenic gene expression in adults

David Melzer, Lorna Harrie, Riccardo Cipelli, William Henley, Cathryn Money, Paul Mccormack, Anita Young, Jack Guralnik, Luigi Ferrucci, Stefania Bandinelli, Anna Maria Corsi, Tamara Galloway

Research output: Contribution to journalArticlepeer-review


Background: Bisphenol A (BPA) is a synthetic estrogen commonly used in polycarbonate plastic and resin-lined food and beverage containers. Exposure of animal and cell models to doses of BPA below the recommended tolerable daily intake (TDI) of 50 μg/kg/day have been shown to alter specific estrogen-responsive gene expression, but this has not previously been shown in humans. Objective: We investigated associations between BPA exposure and in vivo estrogenic gene expression in humans. Methods: We studied 96 adult men from the InCHIANTI population study and examined in vivo expression of six estrogen receptor, estrogen-related receptor, and androgen receptor genes in peripheral blood leukocytes. Results: The geometric mean urinary BPA concentration was 3.65 ng/mL [95% confidence interval (CI): 3.13, 4.28], giving an estimated mean excretion of 5.84 μg/day (95% CI: 5.00, 6.85), significantly below the current TDI. In age-adjusted models, there were positive associations between higher BPA concentrations and higher ESR2 [estrogen receptor 2 (ER beta)] expression (unstandardized linear regression coefficient = 0.1804; 95% CI: 0.0388, 0.3221; p = 0.013) and ESRRA (estrogen related receptor alpha) expression (coefficient = 0.1718; 95% CI: 0.0213, 0.3223; p = 0.026): These associations were little changed after adjusting for potential confounders, including obesity, serum lipid concentrations, and white cell subtype percentages. Upper-tertile BPA excretors (urinary BPA > 4.6 ng/mL) had 65% higher mean ESR2 expression than did lower-tertile BPA excretors (0-2.4 ng/mL). Conclusions: Because activation of nuclear-receptor-mediated pathways by BPA is consistently found in laboratory studies, such activation in humans provides evidence that BPA is likely to function as a xenoestrogen in this sample of adults.

Original languageEnglish (US)
Pages (from-to)1788-1793
Number of pages6
JournalEnvironmental Health Perspectives
Issue number12
StatePublished - Dec 2011
Externally publishedYes


  • Bisphenol A
  • Endocrine disruption
  • Estrogen receptor-β
  • Estrogen-related receptor-α
  • Human biomonitoring
  • Toxicogenomics

ASJC Scopus subject areas

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


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