Estrogen Inhibits Development of Yolk Veins and Causes Blood Clotting in Transgenic Medaka Fish Overexpressing Estrogen Receptor

• Published in: Zoological science Vol. 19; no. 12; pp. 1355 - 1361
• Main Authors: Kawamura, Toshiyuki, Sakai, Shuichi, Omura, Seiichi, Hori-e, Ryota, Kawahara, Tetsuya, Kinoshita, Masato, Yamashita, Ichiro
• Format: Journal Article
• Language: English
• Published: Japan Zoological Society of Japan 01.12.2002
• Subjects: Animals; Animals, Genetically Modified; blood clotting; Blood Coagulation - drug effects; Egg Yolk - drug effects; Estradiol - pharmacology; Estradiol Congeners - pharmacology; estrogen; estrogen receptor; Estrogens - pharmacology; Ethinyl Estradiol - pharmacology; Gene Expression; Marine; Original s; Oryzias - blood; Oryzias - embryology; Oryzias - genetics; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; Transgenes - genetics; transgenic medaka fish; Veins - drug effects; Veins - growth & development; yolk vein
• ISSN: 0289-0003
• DOI: 10.2108/zsj.19.1355

We established three transgenic medaka fish lines overexpressing the medaka estrogen receptor under the constitutive medaka β-actin promoter. The transgenic embryos became hypersensitive to estrogens (17β-estradiol and 17α-ethinylestradiol), and failed to develop yolk veins while blood clots formed in the blood island within 3 days after exposure to the estrogens. The embryos developed normally if exposed to estrogen after an early neurula stage, suggesting that the sensitive stage is before neurulation. The developmental defects were recovered by incubation with an anti-estrogen, tamoxifen. These results indicate that activation of estrogen receptor caused the estrogen-induced developmental defects. Our results show that the transgenic embryos can be used to assay the blood clotting activity of estrogenic compounds in vivo.