Simmons Rebecca A
Department of Pediatrics Children's Hospital Philadelphia, University of Pennsylvania, PA 19104, USA.
Pediatr Res. 2007 May;61(5 Pt 2):64R-67R. doi: 10.1203/pdr.0b013e3180457623.
Intrauterine growth retardation (IUGR) has been linked to later development of type 2 diabetes in adulthood. An abnormal metabolic intrauterine milieu affects the development of the fetus by permanently modifying gene expression of susceptible cells. Altered gene expression persists after birth, suggesting that an epigenetic mechanism may be responsible for changes in transcription. Uteroplacental insufficiency (IUGR) is associated with hypomethylation and hyperacetylation of genomic DNA in brain and liver of IUGR fetal and juvenile rats. These findings are associated with zinc deficiency that often accompanies fetal growth retardation. Studies in the IUGR rat also demonstrate that an abnormal intrauterine environment induces epigenetic modifications of key genes regulating beta-cell development and experiments directly link chromatin remodeling to suppression of transcription. Dietary protein restriction of pregnant rats causes fetal growth retardation and is associated with hypomethylation of the glucocorticoid receptor (GR) and PPARgamma genes in liver of the offspring. It is postulated that these epigenetic changes result in the observed increase in gene expression of GR and PPARgamma. Future research will be directed at elucidating the mechanisms underlying epigenetic modifications in offspring.
宫内生长受限（IUGR）与成年后患2型糖尿病有关。异常的代谢性宫内环境通过永久性改变易感细胞的基因表达来影响胎儿的发育。出生后基因表达的改变持续存在，这表明表观遗传机制可能是转录变化的原因。子宫胎盘功能不全（IUGR）与IUGR胎儿和幼年大鼠脑和肝脏中基因组DNA的低甲基化和高乙酰化有关。这些发现与常伴随胎儿生长受限的锌缺乏有关。对IUGR大鼠的研究还表明，异常的宫内环境会诱导调节β细胞发育的关键基因发生表观遗传修饰，并且实验直接将染色质重塑与转录抑制联系起来。对怀孕大鼠进行饮食蛋白质限制会导致胎儿生长受限，并与后代肝脏中糖皮质激素受体（GR）和PPARγ基因的低甲基化有关。据推测，这些表观遗传变化导致了观察到的GR和PPARγ基因表达增加。未来的研究将致力于阐明后代表观遗传修饰的潜在机制。
