Prenatal nicotine exposure induces epigenetic alterations in the Notch signaling genes in the proximal colon in rats.

BACKGROUND: Prenatal nicotine exposure (PNE) has been shown to significantly impact fetal development, leading to various pathologies in adulthood. OBJECTIVES: In this study, we analyzed the epigenetic effects of PNE on the proximal colon. RESULTS: We show here that PNE decreases the length of the colon crypts and induces a higher Ki-67 index. The genes related to metabolic pathways, tight junctions, and neurodegenerative processes were downregulated in PNE colons, and genes related to inflammation and oxygen transporter activity were upregulated. We observed a decrease in acetylated H4Ac and H3K9Ac marks. Genome-wide DNA methylation analysis demonstrated reduced DNA methylation of genes related to cell adhesion and metabolic pathways and increased methylation levels at thermogenesis, GABAergic synapsing, and non-alcoholic fatty liver disease-related genes. The Notch signaling pathway was deregulated in PNE rats. CONCLUSION: PNE leads to perturbation of proximal colon functioning, plausibly through nicotine-induced epigenetic alterations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12864-025-11960-9.