Department of Genetic and Laboratory Medicine, Geneva University Hospital, 1211 Geneva 14, Switzerland.
Reprod Toxicol. 2011 May;31(4):507-12. doi: 10.1016/j.reprotox.2011.02.009. Epub 2011 Mar 5.
Alcohol exposure during pregnancy induces a range of disorders in the offspring. Methylation changes in imprinted genes may play a role in the teratogenic effects of alcohol. We evaluated the possible effects of alcohol administration in pregnant mice on the methylation pattern of 5 imprinted genes (H19, Gtl2, Peg1, Snrpn and Peg3) in somatic and sperm cell DNAs of the male offspring. The effects observed were a 3% (p < 0.005) decrease in the number of methylated CpGs of H19 in the F1 offspring sperm, a 4% (p < 0.005) decrease in the number of methylated CpGs of H19 in the F2 offspring brain and a 26% (p < 0.05) decrease in the mean sperm concentration. CpGs 1 and 2 of the H19 CTCF-binding site 2 exhibited significant methylation percentage losses. H19 CTCF-binding sites are important for the regulation of Igf2 gene expression. The hypomethylation of H19 may contribute to the decreased spermatogenesis in the offspring.
孕期酒精暴露会导致后代出现一系列疾病。印迹基因的甲基化变化可能在酒精的致畸作用中发挥作用。我们评估了在怀孕小鼠中给予酒精对雄性后代体细胞和精子 DNA 中 5 个印迹基因（H19、Gtl2、Peg1、Snrpn 和 Peg3）的甲基化模式的可能影响。观察到的影响是 F1 后代精子中 H19 的甲基化 CpG 数量减少了 3%（p<0.005），F2 后代大脑中 H19 的甲基化 CpG 数量减少了 4%（p<0.005），平均精子浓度降低了 26%（p<0.05）。H19 CTCF 结合位点 2 的 CpG1 和 CpG2 表现出显著的甲基化百分比损失。H19 CTCF 结合位点对于 Igf2 基因表达的调控很重要。H19 的低甲基化可能导致后代精子发生减少。
