Transcriptome and metabolome analysis reveal the effects of Tb (III) exposure on zebrafish (Danio rerio) embryonic development
Year: 2025
Type: article
Abstract: Rare earth elements (REEs) represent emerging environmental contaminants with increasing global concern due to intensive mining activities. This study employed an integrated transcriptomic-metabolomic approach, coupled with an in-depth computational network analysis, to elucidate the systemic toxicity of terbium (Tb³⁺) in zebrafish embryos exposed to environmentally relevant concentrations (0.25-10.0 mg/L). Tb³⁺ exposure induced dose-dependent developmental toxicity, including growth retardation, hyperactive locomotion, and cardiovascular dysfunction. We have performed multi-omics network analysis and identified four critical, high-centrality metabolic hubs that orchestrate this toxicity, including Guanosine monophosphate (GMP), Gamma-Aminobutyric acid (GABA), Linoleic acid, and Prostaglandin E1 (PGE1). Mechanistically, we identified a "Nucleotide-Neuro" axis, where the disruption of the GMP hub was statistically co-regulated (r > 0.86, p < 0.0001) with the downregulation of grin neurotransmitter receptor genes was identified. Furthermore, PGE1 was confirmed to have high connectivity to multiple pathways, statistically linking to key genes in calcium signaling ( camk2d2 ) and lipid energy metabolism ( pnpla3 ). The study also revealed a severe oxidative damage, which was characterized by the concurrent transcriptional suppression of the key defense enzymes CAT and ALDH7A1 despite a high substrate load from the Linoleic acid (lipid peroxidation) hub. These mechanistic insights establish comprehensive toxicity framework for Tb³⁺ and provide scientific foundations for environmental risk assessment of REEs contamination in aquatic ecosystems. • Environmentally relevant Tb³⁺ concentrations (2.0-10.0 mg/L) induce delayed hatching, reduced body length, and teratogenesis in zebrafish embryos. • Growth retardation and malformations are mechanistically linked to a synergistic impairment of both bioenergetic pathways (PGE1- pnpla3 axis) and nucleotide biosynthesis (the GMP hub). • A "Nucleotide-Neuro" axis was identified, where GMP hub disruption is statistically co-regulated ( p < 0.0001) with grin neurotransmitter receptor gene expression. • Cardiovascular dysfunction is mechanistically linked to the PGE1 hub, which is statistically correlated with key genes in both calcium signaling ( camk2d2 ). • Tb³⁺ induces a oxidative damage by suppressing the key detoxification enzyme CAT and ALDH7A1 despite high substrate load from lipid peroxidation.
Institution: Jiangxi University of Science and Technology
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,930
OpenAlex ID: W4417504897