東京都健康安全研究センター研究年報

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1 Ann. Rep. Tokyo Metr. Inst. P.H., 54, , 2003 A Low Dose Effects of Bisphenol A on the Ultrastructure of Prostate in Suckling Male Rats Nobutaka FUKUMORI, Kuniaki TAYAMA, Hiroshi ANDO, Yoshikazu KUBO, Norio YANO, Hiroshi TAKAHASHI, Akemichi NAGASAWA, Katsuhiro YUZAWA, Yoshimitsu SAKAMOTO and Akio OGATA Low dose effects of bisphenol A (BPA) on the ultrastructure of ventral prostate in suckling male rats were investigated using thin-section electron microscopy. BPA (0, 0.8, 4, 20, 500 ìg/kg) or 17 -estradiol (E2:100 ìg/kg) dissolved in DMSO were subcutaneously administered to suckling male rats from Day 1 through Day 21 after birth. An increase in secretory granules accompanied by (or coupled with) the disappearance of microvilli on the surface of the glandular epithelium and the proliferation of fibroblasts in the fibromuscular layer of the stroma were observed in the E2-treated rats. The secretory epithelial cell height of the prostate in the rats treated with E2 was essentially unchanged in comparison with those of the rats treated with DMSO only. Though a slight increase in secretory granules in the glandular epithelium was observed in the rats treated with 20 and 500 ìgbpa/kg, the alteration in the stroma was not salient in comparison with that of the rats treated with E2. These findings suggest that a low dose of BPA may exert estrogenic effects on the ventral prostate in suckling male rats at the ultrastructural level. Keywords Abisphenol A 17â-estradiol prostate gland rat electron microscopic observation E2 2,3) E2 DES ABPA 4) BPA 1) 2 20 ìg/kg/day BPA 20 ìg/kg/day 5) DES BPA 6) Tokyo Metropolitan Institute of Public Health 3241, Hyakunincho, Shinjukuku, Tokyo Japan

TAKAHASHI, Akemichi NAGASAWA, Katsuhiro YUZAWA, Yoshimitsu SAKAMOTO and Akio OGATA Low dose effects of bisphenol A (BPA) on the ultrastructure of ventral prostate in suckling male rats were

2 348 Ann. Rep. Tokyo Metr. Inst. P.H., 54, 2003 BPA E2 Fig.2 BPA Lot No GG01 dimethyl- sulfoxidedmso Lot No Fig.3b E ìg/kg DMSO 100 ìg/kg E2 Lot No 28H0818 DMSO F344 3 DMSO BPA E2 Fig.4 Fig.6 BPA DMSO Fig.4 4 ìg/kg g 1 ìl 22 BPA 2.5 % 0.1M RER 3 1 % ph7.30.1m 2 BPA % ì g/kg Fig.5 QY-1 Polybed 812 Araldite SER Fig.5 70 nm kv 20 ìg/kg H-7000 RER RER E2 Fig ìg/kg Fig.1 DMSO RER 20 ìg/kg 0.8 RER ì g/kg Fig Fig.3a E2 Fig.8

6 BPA DMSO 1 5 1 Fig.4 4 ìg/kg 21 1 1 1g 1 ìl 22 BPA 2.5 % 0.1M RER 3 1 % ph7.30.1m 2 BPA 20 50 % ì g/kg Fig.

3 54, BPA ìg/kg E ìg/kg BPA 20 ìg/kg á estradiol benzoate vom Saal 8) estradiol cypionate 5 E ìg/kg 3 DES20 200ìg/kg E2 8 (300ìg/kg) E2 E2 9) 3 4) ìg/kg BPA 1 ìg/kg RER 100 ìg/kg 10) 5) 2,3) E2 RER ìg/kg BPA BPA E2 BPA RER 11) BPA E ìg/kg 1 mg/kg estradiol valerate 10 BPA E ìg/kg E2 estradiol valerate BPA 7) estradiol valerate BPA estradiol valerate 7) 25 ìg/kg estradiol benzoate 1 C57BL/6N 12)

DES20 200ìg/kg E2 8 (300ìg/kg) E2 E2 9) 3 4) 11 17 2 20 ìg/kg BPA 1 ìg/kg RER 100 ìg/kg 10) 5) 2,3) E2 RER 220 200

4 350 Ann. Rep. Tokyo Metr. Inst. P.H., 54, ) ) Endocrinology, ) Ann. Anat., ) vom Saal, F.S., Timms, B.G., Montano, M.M., et al. : Proc. Natl. Acad. Sci., ) vom Saal, F, S., Cooke, P.S., Buchanan, D.L., et al. : Toxicol. Ind. Health, ) Ashby, J., Timwell, H. and Haseman, J.,:Regul. Toxicol. Pharm., ) Thompson, S.A., Rowley, D.R. and Heidger, P.M., : Invest. Urol., ) Chang, W.Y., Wilson, M.J., Birch, L., et al. : 9) Kawamura, H., Nonogaki, T., Yoshikawa, K., et al. : 10) Timms, B.G. and Chandler, J. A. : Prostate, ) Nagao, T., Saito, Y., Usumi, K., et al. : Reprod. Toxicol., ) Milman, H.A., Bosland, M.C., Waldem, P.D., et al. : Regul. Toxicol. Pharmacol.,

, 301561661999 7) Thompson, S.A., Rowley, D.R. and Heidger, P.M., : Invest. Urol., 1783891979 8) Chang, W.Y., Wilson, M.J., Birch, L., et al. : 9) Kawamura, H., Nonogaki, T., Yoshikawa, K., et al. : 10) Timms, B.

5 54, Fig.1. Electron micrograph of ventral prostate from a control rat (DMSO). The presence of rough endoplasmic reticulum (RER) and Golgi apparatus (G) are observed in the columnar epithelium. (3,800) Fig.2. Prostate epithelium from a rat treated with estradiol (E2). The increase of secretory granules (Sg) is found near the apical surface. (4,400) Fig.3. Higher magnification of the apical surface of glandular epithelium. The disappearance of microvilli (Mv) and the abundant granules (Sg) are often seen in E2-treatment rat (b) compared to the control (a). (11,000) Fig.4. Prostate epithelium from a rat treated with 4 ì g BPA during suckling. No abnormalities are observed. (4,400)

Prostate epithelium from a rat treated with estradiol (E2). The increase of secretory granules (Sg) is found near the apical surface. (4,400) Fig.3.

6 352 Ann. Rep. Tokyo Metr. Inst. P.H., 54, 2003 Fig.5. Prostate epithelium from a rat treated with 20 ì g BPA. A number of secretory granules (Sg) are present at the apical surface of glandular epithelium. The microvilli are scarcely observed. ( 3,800) Fig.6. Prostate epithelium from a rat treated with a high dose of 500 ìg BPA. Some alteration are similarly observed in comparison with a 20 ìg BPA-treated rat. (4,400) Fig.7. Electron micrograph of stroma from a control rat prostate gland. Fibroblast and collagen fiber are present at periductal matrix. (3,000) Fig.8. Prostatic stroma from a rat treated with E2. The increased smooth muscle becomes more electron dense. (3,000)

Prostate epithelium from a rat treated with a high dose of 500 ìg BPA. Some alteration are similarly observed in comparison with a 20 ìg BPA-treated rat. (4,400) Fig.7.

東京都健康安全研究センター研究年報

東京都健康安全研究センター研究年報 Ann. Rep. Tokyo Metr. Inst. P.H., 55, 2004 透過電子顕微鏡による広視野観察のための試料作製法の検討 Specimen Preparation for Wide Area Observation Using Transmission Electron Microscope Nobutaka FUKUMORI and Akio OGATA Keywords wide