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

Prenatal nicotine exposure (PNE) has been shown to significantly impact fetal development, leading to various pathologies in adulthood. In this study, we analyzed the epigenetic effects of PNE on the proximal colon. 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. PNE leads to perturbation of proximal colon functioning, plausibly through nicotine-induced epigenetic alterations.