J Hazard Mater. 2025 Oct 13;499:140095. doi: 10.1016/j.jhazmat.2025.140095. Online ahead of print.
ABSTRACT
Adolescent neuropsychiatric disorders impose a major global health burden. Bisphenol B (BPB), a prevalent endocrine disruptor in maternal biospecimens, remains an unexamined risk factor. Whether environmentally relevant exposures elicit sex-specific effects or involve long non-coding RNA (lncRNA)-mediated mechanisms is still largely unknown. Using animal models and behavioral assessments, we demonstrated that prenatal BPB exposure at environmentally relevant doses induced male offspring-specific depression- and anxiety-like behaviors, accompanied by alterations in synaptophysin and glutamatergic postsynaptic densities in the cortex. Cortical transcriptomics identified that differentially expressed genes were primarily enriched in neuropeptide signaling, G protein-coupled receptor pathways, and synaptic transmission. Key neuropeptide genes (Gal, Galr1, Oxt, Cartpt) and their corresponding neurotransmitter receptors were downregulated postnatally. Mechanistically, through integrated molecular docking, transcription factor prediction, and competitive endogenous RNA (ceRNA) network construction, we found that BPB may bind to Tcf4/Neurog2/Sp9 and thereby suppressed the expression of lncRNA NONMMUT096884.1, which in turn reduced the expression of neuropeptide-related genes (Galr1 and Oxt) via the ceRNA mechanism, ultimately impairing synaptic transmission and contributing to anxiety/depression-like behaviors in male offspring. This study uncovers previously unrecognized lncRNA-mediated epigenetic pathways underlying sex-biased susceptibility to environmental BPB exposure, providing novel biomarkers and therapeutic targets for neuropsychiatric disorders.
PMID:41106005 | DOI:10.1016/j.jhazmat.2025.140095
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