Are environmental levels of gabapentin (GBP) a cause for concern? Chronic reproductive effects of GBP in zebrafish.

GBP, a widely used antiepileptic drug, is frequently detected in aquatic environments due to inefficient removal in wastewater treatment. This study investigates the chronic reproductive toxicity of GBP in zebrafish (Danio rerio), a model species for endocrine disruption. Exposure began at 20 days post-fertilization (dpf), coinciding with sex differentiation, and continued for 130 days at environmentally relevant concentrations (1, 10, and 100 μg/L). Our results demonstrated that chronic GBP exposure, even at 1 μg/L, significantly impaired reproductive health in zebrafish, including gonadal development, reduced fecundity, and even the developmental success in the F1 generation. Gene expression analysis revealed alterations in key genes of the hypothalamic-pituitary-gonadal (HPG) axis, resulting in sex-dependent hormonal dysregulation. These findings highlight the potential ecological risks of GBP contamination, where even low concentrations can profoundly affect fish reproduction. The study emphasizes the need for further research on pharmaceutical pollutants and their long-term impacts, as well as improved wastewater treatment processes to mitigate pharmaceutical contamination in aquatic ecosystems.