Defining estrogenic mechanisms of bisphenol A analogs through high throughput microscopy-based contextual assays. Academic Article uri icon


  • Environmental exposures to chemically heterogeneous endocrine-disrupting chemicals (EDCs) mimic or interfere with hormone actions and negatively affect human health. Despite public interest and the prevalence of EDCs in the environment, methods to mechanistically classify these diverse chemicals in a high throughput (HT) manner have not been actively explored. Here, we describe the use of multiparametric, HT microscopy-based platforms to examine how a prototypical EDC, bisphenol A (BPA), and 18 poorly studied BPA analogs (BPXs), affect estrogen receptor (ER). We show that short exposure to BPA and most BPXs induces ER and/or ER loading to DNA changing target gene transcription. Many BPXs exhibit higher affinity for ER and act as ER antagonists, while they act largely as agonists or mixed agonists and antagonists on ER. Finally, despite binding to ERs, some BPXs exhibit lower levels of activity. Our comprehensive view of BPXs activities allows their classification and the evaluation of potential harmful effects. The strategy described here used on a large-scale basis likely offers a faster, more cost-effective way to identify safer BPA alternatives.

published proceedings

  • Chem Biol

altmetric score

  • 44.756

author list (cited authors)

  • Stossi, F., Bolt, M. J., Ashcroft, F. J., Lamerdin, J. E., Melnick, J. S., Powell, R. T., ... Mancini, M. A.

citation count

  • 53

complete list of authors

  • Stossi, Fabio||Bolt, Michael J||Ashcroft, Felicity J||Lamerdin, Jane E||Melnick, Jonathan S||Powell, Reid T||Dandekar, Radhika D||Mancini, Maureen G||Walker, Cheryl L||Westwick, John K||Mancini, Michael A

publication date

  • June 2014