Dietary protein restriction during F0 pregnancy in rats induces transgenerational changes in the hepatic transcriptome in female offspring.

Dietary protein restriction during F0 pregnancy in rats induces transgenerational changes in the hepatic transcriptome in female offspring.
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DOI:
10.1371/journal.pone.0021668
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Burdge GC
Burdge GC
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hoile SP;Lillycrop KA;Thomas NA;Hanson MA;Burdge GC

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有相当多的证据表明,在发育过程中,环境暴露诱导的表型在几代人之间存在非基因组传递,尽管其机制尚不清楚。我们研究了在F1代后代中通过在妊娠期间喂食F0代母鼠蛋白质限制(PR)饮食诱导的肝脏转录组表达的改变是否会传递给随后的两代。F0蛋白质限制(PR)和蛋白质充足(PS)母鼠的成年雌性后代之间差异的基因数量为F1 1,684个基因,F2 1,680个基因和F3 2,062个基因。在所有三代中改变的113个基因中,有63个在代间表现出方向相反的差异。与F1相比,F3中上调基因的比例有增加的趋势。KEGG分析表明,在所有三代中,只有粘附连接途径发生了改变。PR后代在所有三代中都表现出空腹血糖稳态的改变和磷酸烯醇式丙酮酸羧激酶启动子甲基化和表达的变化。这些发现表明,F0妊娠期间的饮食挑战诱导所有三代的基因表达改变,但相对较少的基因显示出世代之间的表达改变的传递。对于大多数改变的基因,这些变化并没有在所有世代中发现,包括一些基因在F3中发生了变化,但在F1中没有发生变化,或者PR和PS之间的差异方向和幅度在世代之间存在差异。这种变化可能反映了胎儿从母亲那里接收到的信号在世代之间的差异,这是由于她的表型和环境之间的相互作用发生了变化。
There is considerable evidence for non-genomic transmission between generations of phenotypes induced by environmental exposures during development, although the mechanism is poorly understood. We investigated whether alterations in expression of the liver transcriptome induced in F1 offspring by feeding F0 dams a protein-restricted (PR) diet during pregnancy were passed with or without further change to two subsequent generations. The number of genes that differed between adult female offspring of F0 protein-restricted (PR) and protein-sufficient (PS) dams was F1 1,684 genes, F2 1,680 and F3 2,062. 63/113 genes that were altered in all three generations showed directionally opposite differences between generations. There was a trend toward increased proportions of up-regulated genes in F3 compared to F1. KEGG analysis showed that only the Adherens Junctions pathway was altered in all three generations. PR offspring showed altered fasting glucose homeostasis and changes in phosphoenolpyruvate carboxykinase promoter methylation and expression in all three generations. These findings show that dietary challenge during F0 pregnancy induced altered gene expression in all three generations, but relatively few genes showed transmission of altered expression between generations. For the majority of altered genes, these changes were not found in all generations, including some genes that were changed in F3 but not F1, or the direction and magnitude of difference between PR and PS differed between generations. Such variation may reflect differences between generations in the signals received by the fetus from the mother as a consequence of changes in the interaction between her phenotype and the environment.
DOI: 10.3945/jn.109.104653
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