MOE Joint International Research Laboratory of Animal Health & Food Safety, Nanjing Agricultural University, Nanjing, P. R. China.
Key Laboratory of Animal Physiology & Biochemistry, Nanjing Agricultural University, Nanjing, P. R. China.
J Sci Food Agric. 2020 Mar 15;100(4):1486-1494. doi: 10.1002/jsfa.10156. Epub 2019 Dec 18.
We reported previously that maternal betaine promotes hepatic insulin-like growth factor (IGF2) expression in F1 offspring rats through hypermethylation of the IGF2/H19 imprinting control region (ICR). It remains unknown whether this acquired trait can be transmitted to the F2 generation. This study aimed to determine whether dietary betaine supplementation to grand dams affects the hepatic IGF2 expression in F2 rat offspring and how it is related to alterations in DNA methylation. F2 rat offspring derived from grand dams fed basal or betaine-supplemented diet (10 g kg ) were examined at weaning. Serum IGF2 concentration was measured with enzyme-linked immunosorbent assay (ELISA). Hepatic expression of IGF2, together with other proliferation and apoptosis markers, was determined by using quantitative polymerase chain reaction (qPCR), western blot, and immunohistochemistry. The methylation status of the IGF2/H19 ICR and the promoters of IGF2 gene were detected by methylated DNA immunoprecipitation quantitative polymerase chain reaction (MeDIP-qPCR).
The maternal betaine-induced up-regulation of hepatic IGF2 expression in F1 rat offspring was transmitted to the F2 generation. The F2 rats from the betaine group demonstrated enhanced hepatic IGF2 expression at both mRNA and protein levels, in association with higher serum IGF2 concentration. No alterations were observed in the ICR methylation of the IGF2/H19 locus, and hypomethylation was detected in promoters of IGF2 gene in betaine group.
These results indicate that maternal betaine enhances hepatic IGF2 expression in F2 rat offspring through modification of DNA methylation on IGF2 promoters. © 2019 Society of Chemical Industry.
我们之前报道过，母体甜菜碱通过 IGF2/H19 印迹控制区（ICR）的超甲基化促进 F1 代仔鼠肝脏胰岛素样生长因子（IGF2）的表达。但尚不清楚这种获得的性状是否可以传递给 F2 代。本研究旨在确定母体甜菜碱补充是否会影响 F2 代仔鼠肝脏 IGF2 的表达，并探讨其与 DNA 甲基化改变的关系。仔鼠断乳时，检查用基础或甜菜碱补充饮食（10 g/kg）喂养的母鼠所产 F2 代仔鼠。采用酶联免疫吸附试验（ELISA）测定血清 IGF2 浓度。采用实时定量聚合酶链反应（qPCR）、Western blot 和免疫组织化学检测 IGF2、其他增殖和凋亡标志物的肝表达。采用甲基化 DNA 免疫沉淀定量聚合酶链反应（MeDIP-qPCR）检测 IGF2/H19 ICR 和 IGF2 基因启动子的甲基化状态。
母源性甜菜碱诱导的 F1 代仔鼠肝脏 IGF2 表达上调传递给 F2 代。来自甜菜碱组的 F2 大鼠在 mRNA 和蛋白水平上均表现出增强的肝脏 IGF2 表达，同时血清 IGF2 浓度升高。IGF2/H19 基因座的 ICR 甲基化没有改变，在甜菜碱组中 IGF2 基因启动子中检测到低甲基化。
这些结果表明，母体甜菜碱通过 IGF2 基因启动子的 DNA 甲基化修饰增强 F2 代仔鼠肝脏 IGF2 的表达。 © 2019 化学工业协会。
