Toxicogenomic signatures of estrogen-related modes of action in the zebrafish embryo

Endocrine disruptors (EDs) represent a diverse array of chemicals known to interfere with the endocrine systems of both human and environmental organisms, adversely affecting reproduction, development, and behavior, thus raising significant health and ecological concerns. Traditional regulatory tests for endocrine activity typically involve juvenile or adult fish, which is both time-consuming and resource-intensive and necessitates substantial animal use. This study adopts a transcriptomic approach to identify toxicogenomic signatures associated with the disruption of estrogen signaling in zebrafish (Danio rerio) embryos. Utilizing a modified zebrafish embryo toxicity (zFET) test based on Organisation for Economic Co-operation and Development (OECD) test guideline 236, the embryos were exposed to two sublethal concentrations of estradiol, bisphenol A, and fulvestrant. Despite no significant effects on survival or hatching rate were observed in treated groups compared to the controls, our study effectively pinpointed several genes including vtg1, cyp19a1b, fam20cl, sult1st2, pck1, agxtb, hsd17b12a, ptgs2a, and ccn1 as linked to a disruption of estrogen signaling. These genes emerge as promising biomarker candidates for identifying and distinguishing estrogen-related modes of action. Additionally, this approach not only supports the detection of potential endocrine disruptors but also opens up possibilities for prioritizing substances for higher tier endocrine testing, which could substantially reduce animal testing in the future.