Epigenetic changes of hepatic glucocorticoid receptor in sheep male offspring undernourished in utero
Epigenetic changes of hepatic glucocorticoid receptor in sheep male offspring undernourished in utero
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DOI：
10.1071/rd16276
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发表时间：
2017-09-01
影响因子：
1.9
通讯作者：
Plakokefalos, Elias
中科院分区：
文献类型：
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作者：
Chadio, Stella;Kotsampasi, Basiliki;Plakokefalos, Elias
本研究的目的是表征妊娠期间母亲营养不良对肝糖异生酶基因表达的影响，并确定这种影响是否是通过糖皮质激素受体（GR）的表观遗传变化介导的。怀孕母羊从妊娠第0天到第30天（R1）或从妊娠第31天到第100天（R2）饲喂50％营养限制饮食，或在整个妊娠期间饲喂100％饮食（对照）。羔羊分娩后，按食欲喂养。 10个月大时，后代被安乐死并被切除肝脏。母亲营养不良不会影响后代出生时或 10 个月大时的体重。然而，R2 组雄性的肝脏重量低于其他组（P < 0.05）。在 R2 组的雄性中发现肝脏 GR 启动子显着（P < 0.05）低甲基化，在 R1 组中也有相同的趋势，同时两个限制组中的 GR 基因表达增加（P < 0.001）。两个营养不良组雄性羔羊的肝磷酸烯醇丙酮酸羧激酶 (PEPCK) 基因表达显着增加 (P < 0.05)，并伴有蛋白质水平增加 (P < 0.01)，而葡萄糖 6-磷酸酶 (G6Pase) mRNA 丰度和蛋白质水平没有检测到差异。在雌性羔羊中，所研究的任何参数均未观察到组间差异。这些数据代表了生命早期的侮辱可能导致后代持续生理变化的潜在机制。
The aim of this study was to characterise the effects of maternal undernutrition during gestation on hepatic gluconeogenic enzyme gene expression and to determine whether such effects are mediated through epigenetic changes in the glucocorticoid receptor (GR). Pregnant ewes were fed a 50% nutrient-restricted diet from Day 0 to 30 (R1) or from Day 31 to 100 of gestation (R2) or a 100% diet throughout gestation (Control). After parturition lambs were fed to appetite. At 10 months of age offspring were euthanised and livers were removed. Maternal undernutrition did not affect offspring bodyweight at birth or at 10 months of age. However, liver weight of males of the R2 group was lower (P < 0.05) in relation to other groups. A significant (P < 0.05) hypomethylation of the hepatic GR promoter was revealed in males of the R2 group and a tendency towards the same in the R1 group, along with increased (P < 0.001) GR gene expression in both restricted groups. A significant increase (P < 0.05) in hepatic phosphoenolpyruvate carboxykinase (PEPCK) gene expression was found in male lambs of both undernourished groups, accompanied by increased (P < 0.01) protein levels, while no differences were detected for glucose-6-phosphatase (G6Pase) mRNA abundance and protein levels. In female lambs, no differences between groups were observed for any parameter studied. These data represent potential mechanisms by which insults in early life may lead to persistent physiological changes in the offspring.