LncRNA-mRNA integrated networks in the neuroendocrine system of bisphenol a-treated mice induce cellular dysfunctions by disrupting transcriptional homeostasis

Bisphenol A (BPA) is a widely used xenoestrogen that can disrupt neuroendocrine and immune regulation through multiple hormone receptors. This study investigated BPA-induced long non-coding RNA (lncRNA)-mRNA interactions in the cerebral cortex and hypothalamic-pituitary-thyroid (HPT) axis of adult male mice. Transcriptome sequencing and comprehensive lncRNA annotation identified 14,858 novel lncRNA transcripts. Integrated network analysis using weighted gene co-expression network analysis (WGCNA) revealed four distinct tissue-specific modules: neuronal signaling alterations (<i>Tac1</i>, <i>Htr1b</i>, <i>Npy</i>), RNA splicing modifications (<i>Srsf5</i>), PI3K/Akt-mediated cellular dysfunction (<i>Creb5</i>, <i>Cdkn1a</i>), and immune receptor signaling disruptions (<i>Trbv15, Fcrla</i>). These findings suggest that BPA reprograms transcriptional networks in a tissue-specific manner, potentially disrupting hormone-related neurotransmission, metabolic regulation, and immune signaling via lncRNA-mediated mechanisms. Such systems-level reprogramming of the immune-neuroendocrine network (INEN) provides novel mechanistic insights and biomarker candidates for assessing and mitigating the health impacts of environmental endocrine disruptors.