Impact of Maternal Nicotine Exposure on Expression of Myelin-Related Genes in Zebrafish Larvae

Background: Although maternal smoking during pregnancy disrupts offspring development, it is not clear whether smoking before pregnancy has any effect on the next generation. Given that nicotine, the major psychoactive component in cigarettes, is toxic to many organs, we hypothesized that maternal smoking even before a pregnancy affects offspring development. Myelin is an important structure in the nervous system, and deficits in myelin are related to many psychiatric disorders and drug addiction. We therefore examined the effect of maternal exposure to nicotine on the expression of myelin genes in the offspring using zebrafish as a model. Methods: Female adult zebrafish were exposed to nicotine through water at a concentration of 1, 5, 10, 15, 20, 25, or 30 mu M (nicotine base) for either 1 h or a continuous 24 h each day for 4 months. The nicotine-treated females were then bred with drug-naive males, and the embryos and larvae were grown in a nicotine-free environment. Maternal survival rates were calculated. Larvae of those exposed to nicotine at a dose of 1, 5, 10, 15, or 20 mu M for 24 h each day were collected at 4, 7, or 14 days postfertilization (dpf). The mRNA expression of myelin-related genes was examined using quantitative RT-PCR. Results: The mRNA expression of most genes encoding myelin major proteins increased with age. These genes were generally downregulated by maternal nicotine exposure in 4 dpf larvae, whereas they were upregulated in 14 dpf larvae. The expression of myelin-related transcription regulators correlated well with that of myelin major proteins. Conclusions: Prepregnancy nicotine exposure altered myelin gene expression in the offspring, implying that maternal smoking before pregnancy affects the next generation.