Abstract: Objective To investigate the influence of gestational arsenic (As) exposure on the neurodevelopment of offspring mice and to elucidate the regulatory role of microRNAs (miRNAs) therein. Methods A murine model of gestational As exposure was established by administering sodium arsenite to pregnant dams via drinking water (at a dose of 0.5 mg/kg body weight). Neurobehavioral alterations in the offspring at postnatal day 30 (Pnd 30) were assessed using the tail suspension test, forced swim test, open field test, and Morris water maze. On Pnd 1, brain tissues of the neonatal mice were collected for histopathological examination of the hippocampal region by hematoxylin and eosin (H&E) staining. MiRNA sequencing was performed to identify differentially expressed miRNAs, followed by Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of their target genes. Results In comparison with the control group, offspring from the As-exposure group exhibited significant anxiety-and depression-like behaviors, alongside impaired learning and memory capabilities (all P<0.05). Histopathological analysis revealed a reduction in neuronal count and a disordered arrangement of neurons in the hippocampal dentate gyrus and CA3 region. MiRNA sequencing identified 69 differentially expressed miRNAs (27 upregulated, 42 downregulated; P<0.05). Bioinformatic analysis indicated that the target genes of these miRNAs were primarily enriched in functions related to nervous system development, regulation of biological processes, and calcium ion transport. These genes were implicated in signaling pathways crucial for neurogenesis, immune regulation, carcinogenesis, and oxidative stress. Conclusion Gestational exposure to arsenic may induce neurobehavioral abnormalities in offspring by modulating aberrant miRNA expression, which in turn affects neuronal development and associated signaling pathways. These findings suggest a pivotal regulatory role for miRNAs in the mechanisms of arsenic-induced neurotoxicity.

Key words: Gestational arsenic exposure, Neurodevelopmental toxicity, Transcriptome sequencing, miRNA