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  3. Prenatal BPB exposure at environmentally relevant dose induces male-specific neuropsychiatric disorders: Impaired neuropeptide-mediated synaptic transmission via lncRNA-dependent ceRNA networks

Prenatal BPB exposure at environmentally relevant dose induces male-specific neuropsychiatric disorders: Impaired neuropeptide-mediated synaptic transmission via lncRNA-dependent ceRNA networks

  • J Hazard Mater. 2025 Oct 13:499:140095. doi: 10.1016/j.jhazmat.2025.140095.
Senlin Xue 1,  Nannan Chen 2,  Yuetong Liu 3,  Xueyi Cai 2,  Yu Shen 4,  Huifeng Yue 5,  Wei Yan 6
Affiliations

Affiliations

  • 1 Xuzhou Engineering Research Center of Medical Genetics and Transformation, Key Laboratory of Genetic Foundation and Clinical Application, Department of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China; Department of Key Laboratory, Affiliated Changshu Hospital of Nantong University, Changshu 215500, PR China.
  • 2 Xuzhou Engineering Research Center of Medical Genetics and Transformation, Key Laboratory of Genetic Foundation and Clinical Application, Department of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
  • 3 School of Nursing, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China.
  • 4 School of Environment and Spatial Informatics, China University of Mining and Technology, Xuzhou, Jiangsu 221116, PR China.
  • 5 Shanxi Key Laboratory of Coal-based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan, Shanxi 030006, China. Electronic address: yuehuifeng@sxu.edu.cn.
  • 6 Xuzhou Engineering Research Center of Medical Genetics and Transformation, Key Laboratory of Genetic Foundation and Clinical Application, Department of Genetics, Xuzhou Medical University, Xuzhou, Jiangsu 221004, PR China. Electronic address: yanwei@xzhmu.edu.cn.
PMID: 41106005 DOI: 10.1016/j.jhazmat.2025.140095
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.

Keywords

Anxiety and depression-like behavior; LncRNAs, ceRNA network; Neuropeptide-mediated synaptic transimission; Prenatal BPB exposure.

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