While the negative impacts of endocrine-disrupting chemicals (EDCs) on reproductive health are well recognised, they can only be properly identified and their risks mitigated using accurate and biologically relevant assays. Furthermore, assays need to be high throughput and practicable to cope with the burgeoning number of chemicals with potential endocrine disrupting action. Our understanding of endocrine signalling and mechanisms of EDC action has evolved greatly in recent decades, however in the field of EDC testing the application of such knowledge is lacking.
We applied contemporary advances in endocrine signalling to develop a novel high-throughput EDC assay able to be used for a broad range of sample types. This assay assesses multiple endocrine signalling pathways and their interactions, simultaneously. As a test case, we assessed a common herbicide, atrazine, for EDC activity by assessing pathway-specific markers of endocrine activation at single-cell resolution in vitro. Previous studies have shown that atrazine acts via interference with hormone metabolism, however other evidence suggests direct actions of atrazine on estrogen receptor alpha (ERa) signalling. This latter activity is not detectable using current high-throughput technologies. Our improved assay clearly detected the ability of atrazine to rapidly activate ERa.
This study demonstrates that applying more biologically-relevant contexts and integrating a broader understanding of endocrine signalling can improve the specificity of EDC detection in a high-throughput assay. An improved EDC detection assay will benefit researchers and legislators in mitigating the negative health and ecological impacts of EDCs.