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

Abstract

We established three transgenic medaka fish lines overexpressing the medaka estrogen receptor under the constitutive medaka beta-actin promoter. The transgenic embryos became hypersensitive to estrogens (17 beta-estradiol and 17alpha-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.