| In Vivo Imaging of Activated Estrogen Receptors in Utero by Estrogens and Bisphenol A Josephine G. Lemmen,1,* Roel J. Arends,2 Paul T. van der Saag,1 and Bart van der Burg1,** 1Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan, Utrecht, the Netherlands; 2Department of Pharmacology, NV Organon, Oss, The Netherlands
Abstract
Environmental estrogens are of particular concern when exposure occurs during embryonic development. Although there are good models to study estrogenic activity of chemicals in adult animals, developmental exposure is much more difficult to test. The weak estrogenic activity of the environmental estrogen bisphenol A (BPA) in embryos is controversial. We have recently generated transgenic mice that carry a reporter construct with estrogen-responsive elements coupled to luciferase. We show that, using this in vivo model in combination with the IVIS imaging system, activation of estrogen receptors (ERs) by maternally applied BPA and other estrogens can be detected in living embryos inutero. Eight hours after exposure to 1mg/kg BPA, ER transactivation could be significantly induced in the embryos. This was more potent than would be estimated from in vitro assays, although its intrinsic activity is still lower than that of diethylstilbestrol and 17ß-estradiol dipropionate. On the basis of these results, we conclude that the estrogenic potency of BPA estimated using invitro assays might underestimate its estrogenic potential in embryos. Key words: bisphenol A, estrogen receptor, in utero, in vivo, reporter mice. Environ Health Perspect 112: 1544-1549 (2004) . doi:10.1289/ehp.7155 available via http://dx.doi.org/ [Online 21 July 2004]
Address correspondence to P. van der Saag, Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan 8, 3584 CT Utrecht, the Netherlands. Telephone: 31-30-2121800. Fax: 31-30-2516464. E-mail: paul@niob.knaw.nl *Current address: Laboratory of Reproductive Biology, Juliane Marie Center for Children, Women and Reproduction, University Hospital of Copenhagen, Copenhagen, Denmark. **Current address: BioDetection Systems BV, Badhuisweg 3, 1031 CM Amsterdam, the Netherlands. This study was supported financially by the European Union fifth framework: QLK4-2000-00305, "The Impact of Developmental Exposure to Weak (Environmental) Estrogens on the Incidence of Diseases in Target Organs Later in Life." It does not necessarily reflect its views and in no way anticipates the commission's future policy in this area. The authors declare they have no competing financial interests. Received 5 April 2004 ; accepted 21 July 2004.
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