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ORIGINAL RESEARCH ARTICLE

Gene Expression Change in the Müllerian Duct of the Mouse Fetus Exposed to Diethylstilbestrol In Utero

Atsuko Suzuki^*,,,, Hiroshi Urushitani^,, Tomomi Sato^||, Tomohiro Kobayashi^¶, Hajime Watanabe^,,#, Yasuhiko Ohta^, and Taisen Iguchi^,,#,1

^* United Graduate School of Veterinary Science, Yamaguchi University, Yoshida 753-8515, Japan; Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, Higashiyama, Myodaiji, Okazaki 444-8787, Japan; Core Research for Evolutional Science and Technology, Japan Science and Technology, Kawaguchi 332-0012, Japan; Laboratory of Experimental Animals, Department of Veterinary Medicine, Faculty of Agriculture, Tottori University, Koyama 680-8553, Japan; ^|| Graduate School of Integrated Science, Yokohama City University, Seto, Kanazawa-ku, Yokohama 236-0027, Japan; ^¶ Department of Pharmacology, GlaxoSmithKline K.K., Wadai 43, Tsukuba, Ibaraki, 300-4247, Japan; and ^# Department of Basic Biology, School of Life Science, Graduate University for Advanced Studies, Higashiyama, Myodaiji, Okazaki 444-8787, Japan

To whom requests for reprints should be addressed at ¹ Okazaki Institute for Integrative Bioscience, National Institute for Basic Biology, National Institutes of Natural Sciences, 5–1 Higashiyama, Myodaiji, Okazaki 444-8787, Japan. E-mail: taisen{at}nibb.ac.jp

In utero exposure to diethylstilbestrol (DES) induces various abnormalities in the Müllerian duct of the mouse. In order to understand the underlying molecular mechanisms associated with DES-induced abnormalities of the Müllerian duct, gene expression was examined on Gestation Day (GD) 19 in mouse fetuses exposed to DES (67 µg/kg body weight) from GDs 10 to 18. Microarray analysis revealed that 387, 387, and 225 genes were upregulated and 177, 172, and 75 genes were downregulated by DES in the oviduct, uterus, and vagina, respectively. DES exposure in utero commonly upregulated 72 genes and downregulated 15 genes in these three organs. The present study demonstrated that organ-specific gene expression patterns in the mouse Müllerian duct were altered by in utero DES exposure. DES-induced changes in expression of genes such as Dkk2, Nkd2, and sFRP1 as well as changes in genes of the Hox, Wnt, and Eph families in the female mouse fetal reproductive tract could be the basis for various abnormalities in reproductive tracts following exposure to this estrogenic drug.

Key Words: microarray • gene expression • diethylstilbestrol • oviduct • uterus • vagina • mouse

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