胎源性疾病发生中表观遗传学变化的研究进展

The Research Advances in Epigenetic Mechanism of Embryonic-derived Diseases

近年来,多项针对"健康与疾病的发育起源(DOHa D)"学说展开的动物实验及流行病学调查研究发现,DNA甲基化、组蛋白修饰及非编码RNA的转录调控等表观遗传修饰可能是引发胎源性疾病的重要机制之一,如nr3c1和11β-hsd-2基因的异常甲基化可影响胎儿神经系统的发育,导致其出生后神经行为的异常即抑郁症、精神分裂症等精神障碍的发生;而组蛋白脱乙酰酶3(HDAC3)可引起胎儿第二心室发育过程中的形态缺陷及细胞外基质异常,与人类先天性心脏病的发病直接相关。现就胎源性疾病发生中表观遗传学变化的研究进展进行综述,可为部分胎源性疾病的预防及临床诊断与治疗提供重要的理论基础及可靠的实验依据。

In recent years, a number of animal experiments and epidemiological studies focused on the ＂Developmental Origins of Health and Disease（DOHa D）＂ theory have revealed that the DNA methylation, histone modification, the transcriptional regulation of non-coding RNA and other epigenetic modifications may play important roles in the development of embryonic-derived disease. Abnormal methylation of nr3c1 and 11β-hsd-2gene affects the development of fetal nervous system, resulting in postnatal neurobehavioral depression,schizophrenia and other mental disorders. Histone deacetylase HDAC3 in the development of the second ventricle is correlated to the onset of human congenital heart disease, including morphological defects in the second ventricular development and extracellular matrix abnormalities. This review summarizes the research advances in epigenetic changes based on the development of embryonic-derived disease in order to provide reliable theoretical and experimental evidences for the prevention, clinical diagnosis and treatment of some embryonic-derived diseases.