Dose-dependent effects of dibutyl phthalate on embryonic development in zebrafish (Danio rerio): The value of integrating concentration gradients in transcriptomic analyses

This study investigates the effects of dibutyl phthalate (DBP)—a plasticizer commonly detected in surface waters worldwide—on zebrafish (Danio rerio) embryos exposed to a concentration gradient from 0 to 120 hours post-fertilization ('protuding mouth' stage). The primary objective was to assess the utility of integrating concentration gradients into transcriptomic analyses to uncover the mechanisms of action of environmental contaminants, such as DBP. Using this experimental design, dose-response modelling was applied to estimate the sensitivity and shape of transcriptomic responses across the DBP gradient. Following optimized over-representation analysis, we revealed that the retinoid signaling pathway may be the most sensitive pathway affected by DBP during zebrafish development, potentially leading to significant morphological changes. Overall design: mRNA-seq profiling of whole zebrafish (Danio rerio) embryos (AB strain) exposed to a dose-gradient [0-5-10-50-100 µg/L] of dibutyl phthalate (DBP). The exposition consisted of five replicates of batches of 30 embryos each, exposed from the '256-cell' stage to the 'protuding mouth' stage. Exposition solutions were prepared as a solvent-free stock solution in fish water.