In vivo imaging of activated estrogen receptors in utero by estrogens and bisphenol A.
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 in utero. Eight hours after exposure to 1 mg/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 17beta-estradiol dipropionate. On the basis of these results, we conclude that the estrogenic potency of BPA estimated using in vitro assays might underestimate its estrogenic potential in embryos.
Lemmen
Josephine G
JG
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Uppsalalaan, Utrecht, The Netherlands.
Arends
Roel J
RJ
van der Saag
Paul T
PT
van der Burg
Bart
B
D000818:Animals; D001559:Benzhydryl Compounds; D004785:Environmental Pollutants / Q000633:toxicity; D004967:Estrogens / Q000633:toxicity; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D008431:Maternal-Fetal Exchange; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology*; D010636:Phenols / Q000633:toxicity*; D011247:Pregnancy; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000502:physiology*; D015203:Reproducibility of Results; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D004785:Environmental Pollutants; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D010636:Phenols; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds