Transcriptomic responses of zebrafish embryos to sublethal exposure to androstenedione: A 96-Hour RNA-seq Study

Endocrine active substances pose risks to both human health and the environment, potentially impacting crucial endocrine-regulated functions like organism development and reproductive capability. However, current testing methods for chemical risk assessment are time-consuming, expensive, and involve extensive animal testing. In its current stance, the European Chemicals Agency (ECHA) advocates for advancing new approach methods (NAMs) to identify endocrine-acting substances (EAS) and non-EAS modalities for endocrine disruption assessment. One such NAM is the transcriptomic point of departure (tPOD) method, leveraging the fact that physiological effects stem from changes in gene expression, detectable through transcriptomic techniques. The tPOD method utilizes compound-induced, concentration-dependent alterations in gene expression to estimate benchmark doses (BMD) for responsive genes. In this study, we focused on determining a tPOD for androgenic activity of androstenedione in zebrafish embryos, correlating it with chronic effects observed in fish literature. Androstenedione, suspected as an endocrine disruptor in non-mammalian organisms, purportedly operates via an androgenic mode of action (MoA).