The prenatal nicotine exposure leads to epigenetic alterations in nervous system signaling genes in the rat

Abstract

Abstract Background. Prenatal nicotine exposure (PNE) has been documented to impose numerous deleterious effects on fetal development. However, the epigenetic changes promoted by nicotine exposure on germ cell are still not well understood. Objectives. In this study, we focused on elucidating the impact of prenatal nicotine exposure on regulatory epigenetic mechanisms important for germ cells development. Methods. Sprague-Dawley rats were exposed to nicotine during pregnancy and male progeny was analyzed at 11 weeks of age. Testis morphology was analyzed using frozen testis sections and expression of germ cell markers was examined by RT-qPCR; regulatory histone modifications were assessed by Western Blot (WB). A genome-wide DNA methylation was analyzed using Methylated DNA immunoprecipitation (MeDIP)-seq. We also carried out transcriptomics analysis in pituitary gland with RNA-seq. Results. We show that gestational exposure to nicotine reduces germ cell numbers, perturbs meiosis, affects the expression of germ line reprogramming responsive genes and impacts the DNA methylation at nervous system genes in the testis. Besides that, PNE leads to perturbation of gene expression in the pituitary gland. Conclusions. Our data demonstrate that PNE leads to perturbation of male spermatogenesis and the observed effects are associated with peripheral nervous system signaling pathway changes. Alterations in the expression of genes associated with diverse roster of biological activities such as cell migration, cell adhesion and GABA signaling in the pituitary gland suggest that effects of nicotine exposure are complex and initiated via alterations in the central nervous system.