Proteomic biomarkers for prenatal bisphenol A-exposure in mouse immune organs.
Many investigators have encountered difficulty in clarifying the risks of exposure to bisphenol A (BPA), an endocrine disrupting chemical in epidemiological studies or animal experiments. In the present study, we developed biomarkers of BPA-induced proteomic alterations in immune organs of mouse offspring that were prenatally exposed to BPA (15 and 300 mg/L of drinking water; they were exposed to 8.9 +/- 1.8 mg of BPA/kg/day and 171.1 +/- 16.8 mg of BPA/kg/day, respectively) that were evaluated in terms of sex, age, and BPA-exposure levels. We performed 2D-gel analyses of samples from various tissues (thymus and spleen), exposure levels, sex, and ages (3- and 7-week-old) (N = 48), and found seven proteins that were altered in a BPA dose-dependent manner. Among them, we further studiedapo-AI, DPPIII, and VAT1, which are suspected to be associated with endocrine disorders. By performing Western blots, we confirmed BPA upregulation of all three proteins. Moreover, the apo-AI mRNA levels were increased in a BPA dose-dependent manner in 3- and 7-week-old female mice. Females and young offspring were somewhat more sensitive to protein alterations than others. Our study, which is based on proteome analyses, suggests that apo-AI, DPPIII, and VAT represent protein biomarkers for BPA and provide useful mechanistic clues for BPA-induced endocrine disruption.
Yang
Mihi
M
Department of Toxicology, Sookmyung Women's University College of Pharmacy, Seoul, Republic of Korea.
Lee
Ho-Sun
HS
Pyo
Myoung-Yun
MY
D000367:Age Factors; D000818:Animals; D016632:Apolipoprotein A-I / Q000096:biosynthesis; D001559:Benzhydryl Compounds; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D051379:Mice; D008813:Mice, Inbred ICR; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000276:immunology; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000276:immunology; D040901:Proteomics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013154:Spleen / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D013950:Thymus Gland / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015854:Up-Regulation; D050493:Vesicular Monoamine Transport Proteins / Q000096:biosynthesis; D000098826:Bisphenol A Compounds
D016632:Apolipoprotein A-I; D001559:Benzhydryl Compounds; D015415:Biomarkers; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; D052244:Endocrine Disruptors; D010636:Phenols; D050493:Vesicular Monoamine Transport Proteins; C100152:dipeptidyl peptidase III; C006780:bisphenol A; D000098826:Bisphenol A Compounds