Novel, highly sensitive, in vivo screening method detects estrogenic activity at low doses of bisphenol A

Abstract

Low doses of bisphenol A (BPA), a typical endocrine-disrupting chemical (EDC), have been reported to exhibit estrogenic action in animals; however, the effects have not been fully clarified because of their non-reproducibility. Here, we developed a novel, short-term screening test for estrogen-like chemicals using in vivo bioluminescence imaging of estrogen-responsive reporter (E-Rep) mice. Comparative studies using 17α-ethinylestradiol and selective estrogen receptor modulators demonstrated that the method provides higher detection sensitivity and requires less time than the uterotrophic bioassay, a well-established, in vivo screening method for estrogen-like chemicals. Our method could detect the estrogenic effects of BPA at doses below tolerable daily intakes, whereas the uterotrophic bioassay could not. Our results indicated that in vivo bioluminescence imaging using E-Rep mice was extremely useful for screening estrogenic chemicals and detecting estrogenic effects at low doses of EDCs, including BPA. Our method should help resolve the controversy about low-dose effects of EDCs.

Keywords: Endocrine disruptor; In vivo imaging; Reporter transgenic mouse; SERMs; Uterotrophic bioassay.