373 BIOLOGICAL EFFECTS OF FETAL EXPOSURE TO BISPHENOL A ON UROGENITAL SINUS

Article Outline

• INTRODUCTION AND OBJECTIVES
• METHODS
• RESULTS
• CONCLUSIONS
• Copyright

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INTRODUCTION AND OBJECTIVES 

In prostate, both androgens and estrogens play a significant role in development and differentiation. Since the balance of these hormones is quite important, even small changes in the levels of estrogens including estrogen-mimicking chemicals can lead to serious changes. Bisphenol A (BPA), one of endocrine disrupting chemicals (EDCs), is well known as a widespread estrogenic chemical. The problem is that BPA has been detected in fetal plasma, implicating in development of toxicity in the fetus. In this study, to investigate the effects of fetal exposure to BPA on prostatic development, we first evaluated the morphological changes of BPA-treated mouse urogenital sinus (UGS). Next, we examined the changes of in situ hormonal environment in BPA-treated UGS.

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METHODS 

From GD13 to GD16, pregnant female C57BL/6 mice were treated with BPA (20 ug/kg/day) or synthetic estrogen diethylstilbestrol (DES, 0.2 ug/kg/day) by oral gavage. On E17-P1 and P5, male UGS were assembled. The E2 level and aromatase activity in UGS were determined by liquid chromatography-tandem mass spectrometry and the tritiated water release assay, respectively.

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RESULTS 

In both BPA- and DES-treated UGS, the number of basal epithelial cells in the primary ducts of dorsolateral prostate was approximately twice as compared with control. The mRNAs of EGF, TGF-alpha, and FGF-7 but not IGF-I were up-regulated. In organ culture analysis, the number of basal epithelial cells was significantly increased in EGF- or TGF-alpha-treated fetal mouse UGS. In analyses of in situ hormonal environment, the E2 level and aromatase activity were significantly increased only in BPA-treated UGS. The mRNA up-regulations of Cyp19a1 (aromatase), Cyp11a1, and Ad4BP/SF-1 were observed. The number of aromatase-positive stromal cells in BPA-treated UGS was approximately twice as compared with control.

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CONCLUSIONS 

Alteration of in situ hormonal environment in UGS may be responsible for prostatic anomalies associated with fetal exposure to EDCs. We demonstrated that BPA had unique action in addition to the common action to estrogen receptor. The common action was the increased number of basal epithelial cells similar to DES treatment, by a suggest mechanism via cellular EGFR signals. On the other hand, the unique action was the increases of in situ E2 level and aromatase activity observed only in BPA treatment. Our data suggested that BPA might interact with in situ steroidogeneis by altering tissue component, e.g., accumulation of aromtase-expressed stromal cells, in particular organs.