Early-life exposure to semicarbazide induced neurodevelopmental toxicity associated with neurotransmitter in Oryzias melastigma.

Abstract

Semicarbazide (SEM) is a hydrazine-derived compound that enters the environment from various sources and exhibits complex toxicological mechanisms. There is growing concern about pollutant-induced toxicity during early development, as well as the long-term effects. In this study, Oryzias melatigma embryos were exposed to 10, 50, and 100μg/L SEM for 14 days then reared in clean water for an additional 90 days until adulthood. Transcriptomic analysis showed that differentially expressed genes were primarily enriched in neurotransmitters and lipid metabolism-related pathways. Specifically, several neurotransmitter system-related gene expressions were perturbed, accompanied by reduced gamma-aminobutyric acid (GABA) and dopamine levels, as well as decreased glutamate decarboxylase (GAD) and acetylcholinesterase (AChE) activity. Altered gene expressions associated with lipid-related pathways suggest a possible link with the lipid metabolism and a potential role of SEM-induced neurodevelopmental effects. Notably, SEM residues were still detected in the liver and brain of adult in the 100μg/L group even after the recovery periods. Abnormal neurotransmitter levels were also observed in adult fish, accompanied by reduced exploratory activity and anxiety-like behavioral changes. Altogether, these findings suggest that SEM-induced developmental neurotoxicity may be associated with disruptions in neurotransmitter homeostasis and metabolic disturbance, and early-life SEM exposure may lead to long-term neurodevelopmental effects even after a recovery period. This study provides new evidence for the neurotoxic effects of SEM exposure in aquatic organisms and highlights the importance of considering pollutant exposure during early development in ecological risk assessments.