Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition.
Progressive, transgenerational changes in offspring phenotype and epigenotype following nutritional transition.
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DOI：
10.1371/journal.pone.0028282
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lillycrop KA
中科院分区：
文献类型：
--
作者：
Burdge GC;Hoile SP;Uller T;Thomas NA;Gluckman PD;Hanson MA;Lillycrop KA
在发育过程中对环境输入做出反应的表型改变的诱导涉及表观遗传变化。表型性状可以通过各种机制在世代之间传递，包括表观遗传状态的直接传递或通过在每一代中诱导表观遗传标记从头开始。为了区分这些可能性，我们测量了暴露在持续环境挑战下的大鼠四代人的表观遗传标记。F0代雌性大鼠的日粮能量在受孕时增加了25%，并维持在这一水平，直到F3代。F0代母猪孕期增重明显高于F1和F2代，而哺乳期增重和摄食量明显低于F1和F2代母猪。在妊娠第8天，F0和F1母猪的空腹血糖浓度高于F2母猪，β-羟丁酸含量低于F2母猪。伴随而来的是磷酸烯醇式丙酮酸羧酸激酶的减少，PPARα和肉碱棕榈酰转移酶1mRNA的表达增加。PEPCK基因的表达与其启动子上特定的CpG二核苷酸甲基化呈负相关。DNA甲基转移酶(Dnmt)3a2，而不是Dnmt1或Dnmt3b在F1~F3代中表达增加，启动子甲基化减少。这些数据表明，孕期和哺乳期一代内能量代谢的调节受上一代母体表型和当前孕期环境的影响。对表型的跨代效应与特定基因的DNA甲基化改变有关，这种方式与每一代表观遗传标记的诱导从头开始一致。
Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and β-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARα and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation.
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影响因子：
3.6
作者：
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通讯作者：
Burdge, Graham C.