Abstract
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.