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Title: Perinatal bisphenol A exposures increase production of pro-inflammatory mediators in bone marrow-derived mast cells of adult mice.

Authors: O'Brien, Edmund; Dolinoy, Dana C; Mancuso, Peter

Published In J Immunotoxicol, (2014 Jul-Sep)

Abstract: Bisphenol A (BPA) is a widely used monomer of polycarbonate plastics and epoxide resin that has been implicated in asthma pathogenesis when exposure occurs to the developing fetus. However, few studies have examined the relationship between perinatal BPA exposure and asthma pathogenesis in adulthood. This study used an isogenic mouse model to examine the influence of perinatal BPA exposure via maternal diet on inflammatory mediators associated with asthma in 6-month-old adult offspring by measuring bone marrow-derived mast cell (BMMC) production of lipid mediators (cysteinyl leukotrienes and prostaglandin D2), cytokines (interleukin [IL]-4, IL-5, IL-6, IL-13, and tumor necrosis factor [TNF]-α), and histamine. Global DNA methylation levels in BMMCs from adult offspring were determined to elucidate a potential regulatory mechanism linking perinatal exposure to mast cell phenotype later in life. Four BPA exposure doses were tested: low (50 ng BPA/kg diet, n = 5), medium (50 μg BPA/kg diet, n = 4), high (50 mg BPA/kg diet, n = 4), and control (n = 3). Following BMMC activation, increases in cysteinyl leukotriene (p < 0.01) and TNFα (p < 0.05) production were observed in all BPA-exposure groups, and increases in prostaglandin D2 (p < 0.01) and IL-13 (p < 0.01) production were observed in the high exposure group. Additionally, BMMCs from adult mice in all exposure groups displayed a decrease in global DNA methylation compared to control animals. Thus, perinatal BPA exposure displayed a long-term influence on mast cell-mediated production of pro-inflammatory mediators associated with asthma and global DNA methylation levels, suggesting a potential for mast cell dysregulation, which could affect pulmonary inflammation associated with allergic airway disease into adulthood.

PubMed ID: 23914806 Exiting the NIEHS site

MeSH Terms: Air Pollutants, Occupational/adverse effects; Animals; Animals, Newborn; Benzhydryl Compounds/administration & dosage*; Benzhydryl Compounds/adverse effects; Bone Marrow Cells/drug effects*; Bone Marrow Cells/physiology; Cytokines/metabolism; DNA Methylation/drug effects; Environmental Exposure/adverse effects; Female; Histamine/metabolism; Inflammation Mediators; Leukotrienes/metabolism; Male; Mast Cells/drug effects*; Mast Cells/physiology; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Phenols/administration & dosage*; Phenols/adverse effects; Pregnancy

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