| The CDC estimates 2 million babies per year are exposed to cigarette smoke (CS), a complex, carcinogenic mixture, during early development. CS is known to alter histone modifications and the methylation patterns of DNA. CS exposure during the delicate periods of fetal and neonatal development may change the expression of critical genes. In this study, pregnant C57BL/6J mice were exposed to 5 mg/m3 mainstream CS for 3 hours/day, 5 days/week until birth. For postnatal exposures, 4 day old mice were exposed to 5 mg/m3 ETS for 3 hours per day, 5 days per week, until day 21 post-partum. Mice were euthanized at 23 days and 11 weeks of age. A microarray was used to analyze global changes in gene expression and the results were confirmed using quantitative PCR. Global methylation was analyzed with a microplate based kit. Histone modifications potentially important for the altered gene expression profiles were examined using chromatin immunoprecipitation and quantitative real time PCR. It was found that upregulation of a DNA repair gene growth arrest and DNA damage inducible gamma 45, a glucose regulating gene glucose-6-phosphatase, catalytic, and an important gene in the circadian rhythm pathway, aryl hydrocarbon receptor like, resulted from both exposures, seen at 23 days and 11 weeks of age. Global methylation analysis revealed hypomethylation in the prenatal exposure but hypermethylation in the postnatal exposure at 23 days. At the 11 week time point, no difference in methylation was found. These experiments show how early developmental exposures to CS can alter gene expression patterns, and it is important to note that these changes persisted as the animals aged. The epigenetic effects of the exposure vary depending on the developmental period in which the exposure occurred and potentially the type of cigarette smoke, mainstream or environmental CS, could play a role in the effects seen as a results of the exposure. This study confirms the need to promote cessation of CS during pregnancy, and also stresses the importance of new mothers remaining smoke-free after birth, as some of the effects of the exposures persisted through aging. |
