title: Perinatal bisphenol A exposures increase production of pro-inflammatory mediators in bone marrow-derived mast cells of adult mice.
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.
authors.affiliation: Department of Environmental Health Sciences, School of Public Health, University of Michigan , Ann Arbor, MI , USA.
authors.forename: Edmund
authors.initials: E
authors.lastname: O'Brien
authors.forename: Dana C
authors.initials: DC
authors.lastname: Dolinoy
authors.forename: Peter
authors.initials: P
authors.lastname: Mancuso
mesh_terms: D000395:Air Pollutants, Occupational / Q000009:adverse effects; D000818:Animals; D000831:Animals, Newborn; D001559:Benzhydryl Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000502:physiology; D016207:Cytokines / Q000378:metabolism; D019175:DNA Methylation / Q000187:drug effects; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D006632:Histamine / Q000378:metabolism; D018836:Inflammation Mediators; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D010636:Phenols / Q000008:administration & dosage* / Q000009:adverse effects; D011247:Pregnancy; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D016207:Cytokines; D006632:Histamine; D018836:Inflammation Mediators; D015289:Leukotrienes; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Bisphenol A; mast cells; pro-inflammatory mediators
references.citation: Endocr Rev. 2009 Feb;30(1):75-95
references.pmid: 19074586
references.citation: Epigenomics. 2009 Oct;1(1):111-117
references.pmid: 20563319
references.citation: J Allergy Clin Immunol. 2010 Sep;126(3):498-504.e1-6
references.pmid: 20816186
references.citation: Allergy. 2010 Feb;65(2):152-67
references.pmid: 19912154
references.citation: Thorax. 2009 Jun;64(6):476-83
references.pmid: 19237391
references.citation: Immunology. 2004 Jul;112(3):489-95
references.pmid: 15196218
references.citation: Semin Fetal Neonatal Med. 2012 Apr;17(2):67-72
references.pmid: 22277111
references.citation: Respir Med. 2012 Jan;106(1):9-14
references.pmid: 22112783
references.citation: Environ Health Perspect. 2008 Apr;116(4):514-9
references.pmid: 18414636
references.citation: J Toxicol Environ Health A. 2012;75(24):1451-5
references.pmid: 23116450
references.citation: Food Chem Toxicol. 2012 Jun;50(6):2109-17
references.pmid: 22446810
references.citation: Mutat Res. 2010 Aug 7;690(1-2):24-39
references.pmid: 19769993
references.citation: Allergy. 2004 May;59(5):469-78
references.pmid: 15080825
references.citation: Toxicol Lett. 2011 Dec 15;207(3):298-305
references.pmid: 21983029
references.citation: PLoS One. 2010 Dec 22;5(12):e14409
references.pmid: 21203555
references.citation: Allergol Immunopathol (Madr). 2010 Mar-Apr;38(2):83-7
references.pmid: 20106581
references.citation: J Biochem Mol Toxicol. 2013 Feb;27(2):116-23
references.pmid: 23208979
references.citation: Thorax. 2012 Jul;67(7):625-31
references.pmid: 22334535
references.citation: Chem Res Toxicol. 2002 Oct;15(10):1281-7
references.pmid: 12387626
references.citation: Drug Chem Toxicol. 2010 Oct;33(4):421-9
references.pmid: 20553123
references.citation: Environ Health. 2012 Feb 21;11:8
references.pmid: 22353195
references.citation: Cien Saude Colet. 2012 Feb;17(2):407-34
references.pmid: 22267036
references.citation: Evid Based Med. 2010 Dec;15(6):190-1
references.pmid: 20861411
references.citation: Arch Toxicol. 2011 Sep;85(9):1035-43
references.pmid: 21287149
references.citation: Reprod Toxicol. 2007 Aug-Sep;24(2):139-77
references.pmid: 17825522
references.citation: Biol Reprod. 2005 Jun;72(6):1344-51
references.pmid: 15689538
references.citation: Environ Mol Mutagen. 2012 Jun;53(5):334-42
references.pmid: 22467340
references.citation: Thorax. 1999 Sep;54(9):825-57
references.pmid: 10456976
references.citation: Arch Intern Med. 2004 Feb 23;164(4):379-86
references.pmid: 14980988
references.citation: J Nutr. 1997 Sep;127(9):1902S-1907S
references.pmid: 9278579
references.citation: Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19881-6
references.pmid: 19064924
references.citation: Environ Toxicol. 2011 Aug;26(4):364-72
references.pmid: 20082445
references.citation: FASEB J. 2013 Apr;27(4):1784-92
references.pmid: 23345456
references.citation: Trends Endocrinol Metab. 2010 Apr;21(4):214-22
references.pmid: 20074974
references.citation: Environ Health Perspect. 2004 Feb;112(2):272-83
references.pmid: 14754583
references.citation: Respir Med. 2012 Sep;106(9):1236-43
references.pmid: 22703945
references.citation: Zhonghua Shi Yan He Lin Chuang Bing Du Xue Za Zhi. 2011 Oct;25(5):368-70
references.pmid: 22338227
references.citation: Environ Health Perspect. 2002 Nov;110(11):A703-7
references.pmid: 12417499
references.citation: Clin Immunol. 2003 Oct;109(1):2-5
references.pmid: 14585270
references.citation: Eur Respir J. 2007 Apr;29(4):793-803
references.pmid: 17400878
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2003 Aug-Sep;69(2-3):195-205
references.pmid: 12895603
references.citation: PLoS One. 2012;7(3):e33853
references.pmid: 22457795
references.citation: Toxicol Sci. 2012 Nov;130(1):82-93
references.pmid: 22821851
references.citation: Proc Natl Acad Sci U S A. 2007 Aug 7;104(32):13056-61
references.pmid: 17670942
references.citation: Proc Natl Acad Sci U S A. 2012 Jan 10;109(2):541-6
references.pmid: 22190484
references.citation: J Allergy Clin Immunol. 2006 Jun;117(6):1277-84
references.pmid: 16750987
references.citation: J Periodontal Res. 2001 Aug;36(4):233-6
references.pmid: 11519696
references.citation: Am J Reprod Immunol. 2004 Jul;52(1):19-26
references.pmid: 15214938
references.citation: Mol Cell Biol. 2003 Aug;23(15):5293-300
references.pmid: 12861015
references.citation: Environ Health Perspect. 2009 Jun;117(6):879-85
references.pmid: 19590677
references.citation: Toxicology. 2000 Sep 7;150(1-3):191-206
references.pmid: 10996675
references.citation: FASEB J. 2011 Oct;25(10):3377-87
references.pmid: 21693622
references.citation: Semin Fetal Neonatal Med. 2012 Apr;17(2):82-91
references.pmid: 22265927
references.citation: Lupus. 1999;8(5):380-3
references.pmid: 10455517
references.citation: Environ Health Perspect. 2010 Feb;118(2):273-7
references.pmid: 20123615
references.citation: Eur J Epidemiol. 2012 Jan;27(1):5-14
references.pmid: 22350146
references.citation: Toxicology. 2006 Sep 21;226(2-3):208-17
references.pmid: 16914249
references.citation: Curr Opin Allergy Clin Immunol. 2013 Feb;13(1):92-9
references.pmid: 23090385
references.citation: Environ Health Perspect. 2011 Apr;119(4):422-30
references.pmid: 20855240
references.citation: Reprod Toxicol. 2007 Aug-Sep;24(2):199-224
references.pmid: 17683900
references.citation: Mol Immunol. 2007 Mar;44(8):1977-85
references.pmid: 17084457
references.citation: Environ Health Perspect. 2011 Mar;119(3):390-6
references.pmid: 21062687
references.citation: Environ Health Perspect. 2007 Jan;115(1):48-52
references.pmid: 17366818
references.citation: Environ Health Perspect. 2005 Apr;113(4):391-5
references.pmid: 15811827
references.citation: Mol Cancer Ther. 2006 Jan;5(1):8-19
references.pmid: 16432158
references.citation: Horm Behav. 2013 Jan;63(1):180-9
references.pmid: 23051835
references.citation: Toxicol Appl Pharmacol. 2010 Sep 1;247(2):158-65
references.pmid: 20600215
references.citation: Cytokine. 2011 Dec;56(3):792-7
references.pmid: 22004920
references.citation: Obesity (Silver Spring). 2010 Feb;18(2):314-21
references.pmid: 19680236
references.citation: J Allergy Clin Immunol. 2003 Aug;112(2):271-82
references.pmid: 12897732
references.citation: Reprod Toxicol. 2012 Aug;34(1):1-7
references.pmid: 22516041
references.citation: BMC Public Health. 2012 Mar 19;12:204
references.pmid: 22429515
references.citation: J Immunol. 1998 Nov 1;161(9):4493-7
references.pmid: 9794373
references.citation: Nat Genet. 1999 Nov;23(3):314-8
references.pmid: 10545949