Single-Cell Dissection of Dimethomorph-Induced Neurotoxicity in the Gestational Brain: Metabolic Disruption and Blood–Brain Barrier Dysfunction

The neurotoxic effects of pesticide residues on nontarget organisms, particularly pregnant women and fetuses, represent a critical concern in environmental and health research. In this study, dimethomorph (DMM) was detected in human cord blood in normal pregnancies at term (without maternal-fetal complications). And neurotoxicity of the fungicide DMM through integrated single-cell RNA sequencing (scRNA-seq) and metabolomic profiling in pregnant mice brain tissue. Our results demonstrate that DMM exposure induces significant alterations in both the proportions and functions of multiple neural cell populations, including microglia, oligodendrocytes, astrocytes, and endothelial cells, accompanied by metabolic reprogramming and blood-brain barrier (BBB) dysfunction. Single-cell analysis revealed cell subtype-specific transcriptional changes and aberrant activation of metabolic pathways (e.g., PI3K-AKT-mTOR signaling), while metabolomic profiling further identified substantial disturbances in amino acid, lipid, and energy metabolism. Furthermore, cell-cell communication analysis indicated enhanced pathological signaling network interactions under DMM exposure. These findings not only elucidate the mechanisms underlying DMM-induced neurotoxicity but also highlight the potential risks of pesticide exposure during pregnancy to maternal and fetal health, providing critical insights for pesticide safety assessment and the development of neuroprotective strategies.