Endocrine disrupter bisphenol a increases in situ estrogen production in the mouse urogenital sinus

Shigeki Arase, Kenichiro Ishii, Katsuhide Igarashi, Kenichi Aisaki, Yuko Yoshio, Ayami Matsushima, Yasuyuki Shimohigashi, Kiminobu Arima, Jun Kanno, Yoshiki Sugimura

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76 Citations (Scopus)


The balance between androgens and estrogens is very important in the development of the prostate, and even small changes in estrogen levels, including those of estrogen-mimicking chemicals, can lead to serious changes. Bisphenol A (BPA), an endocrine-disrupting chemical, is a well-known, ubiquitous, estrogenic chemical. To investigate the effects of fetal exposure to low-dose BPA on the development of the prostate, we examined alterations of the in situ sex steroid hormonal environment in the mouse urogenital sinus (UGS). In the BPAtreated UGS, estradiol (E2) levels and CYP19A1 (cytochrome P450 aromatase) activity were significantly increased compared with those of the untreated and diethylstilbestrol (DES)-treated UGS. The mRNAs of steroidogenic enzymes, Cyp19a1 and Cyp11a1, and the sex-determining gene, Nr5a1, were upregulated specifically in the BPA-treated group. The upregulation of mRNAs was observed in the mesenchymal component of the UGS as well as in the cerebellum, heart, kidney, and ovary but not in the testis. The number of aromatase-expressing mesenchymal cells in the BPA-treated UGS was approximately twice that in the untreated and DEStreated UGS. The up-regulation of Esrrg mRNA was observed in organs for which mRNAs of steroidogenic enzymes were also up-regulated. We demonstrate here that fetal exposure to lowdose BPA has the unique action of increasing in situ E2 levels and CYP19A1 (aromatase) activity in the mouse UGS. Our data suggest that BPA might interact with in situ steroidogenesis by altering tissue components, such as the accumulation of aromatase-expressing mesenchymal cells, in particular organs.

Original languageEnglish
Pages (from-to)734-742
Number of pages9
JournalBiology of reproduction
Issue number4
Publication statusPublished - Apr 1 2011

All Science Journal Classification (ASJC) codes

  • Reproductive Medicine
  • Cell Biology


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