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首页> 外文期刊>Endocrinology >Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling
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Gestational Diabetes Alters Offspring DNA Methylation Profiles in Human and Rat: Identification of Key Pathways Involved in Endocrine System Disorders, Insulin Signaling, Diabetes Signaling, and ILK Signaling

机译:妊娠糖尿病改变人和大鼠的后代DNA甲基化谱:内分泌系统疾病,胰岛素信号传导,糖尿病信号传导和ILK信号传导的关键途径的鉴定

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摘要

Gestational diabetes is associated with risk for metabolic disease later in life. Using a cross-species approach in rat and humans, we examined the hypothesis that gestational diabetes during pregnancy triggers changes in the methylome of the offspring that might be mediating these risks. We show in a gestation diabetes rat model, the Cohen diabetic rat, that gestational diabetes triggers wide alterations in DNA methylation in the placenta in both candidate diabetes genes and genome-wide promoters, thus providing evidence for a causal relationship between diabetes during pregnancy and DNA methylation alterations. There is a significant overlap between differentially methylated genes in the placenta and the liver of the rat offspring. Several genes differentially methylated in rat placenta exposed to maternal diabetes are also differentially methylated in the human placenta of offspring exposed to gestational diabetes in utero. DNA methylation changes inversely correlate with changes in expression. The changes in DNA methylation affect known functional gene pathways involved in endocrine function, metabolism, and insulin responses. These data provide support to the hypothesis that early-life exposures and their effects on metabolic disease are mediated by DNA methylation changes. This has important diagnostic and therapeutic implications.
机译:妊娠糖尿病与生命后期代谢疾病的风险有关。通过在大鼠和人类中使用跨物种方法,我们检验了以下假设:怀孕期间的妊娠糖尿病会触发可能介导这些风险的后代甲基化组的变化。我们在妊娠糖尿病大鼠模型Cohen糖尿病大鼠中显示,妊娠糖尿病会触发候选糖尿病基因和全基因组启动子中胎盘DNA甲基化的广泛变化,从而为妊娠期间糖尿病与DNA之间的因果关系提供证据甲基化改变。胎盘中的差异甲基化基因与大鼠后代肝脏之间存在明显的重叠。在暴露于母体糖尿病的大鼠胎盘中甲基化的几个基因也在子宫中暴露于妊娠糖尿病的后代的人胎盘中甲基化。 DNA甲基化变化与表达变化成反比。 DNA甲基化的变化影响涉及内分泌功能,代谢和胰岛素反应的已知功能基因途径。这些数据为以下假设提供了依据:DNA甲基化变化介导了生命早期暴露及其对代谢疾病的影响。这具有重要的诊断和治疗意义。

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