Pozharny Yevgeniya, Lambertini Luca, Clunie Garfield, Ferrara Lauren, Lee Men-Jean
Mount Sinai School of Medicine, New York, NY, USA.
Mt Sinai J Med. 2010 Mar-Apr;77(2):225-35. doi: 10.1002/msj.20176.
Epigenetics refers to structural modifications to genes that do not change the nucleotide sequence itself but instead control and regulate gene expression. DNA methylation, histone modification, and RNA regulation are some of the mechanisms involved in epigenetic modification. Epigenetic changes are believed to be a result of changes in an organism's environment that result in fixed and permanent changes in most differentiated cells. Some environmental changes that have been linked to epigenetic changes include starvation, folic acid, and various chemical exposures. There are periods in an organism's life cycle in which the organism is particularly susceptible to epigenetic influences; these include fertilization, gametogenesis, and early embryo development. These are also windows of opportunity for interventions during the reproductive life cycle of women to improve maternal-child health. New data suggest that epigenetic influences might be involved in the regulation of fetal development and the pathophysiology of adult diseases such as cancer, diabetes, obesity, and neurodevelopmental disorders. Various epigenetic mechanisms may also be involved in the pathogenesis of preeclampsia and intrauterine growth restriction. Additionally, environmental exposures are being held responsible for causing epigenetic changes that lead to a disease process. Exposure to heavy metals, bioflavonoids, and endocrine disruptors, such as bisphenol A and phthalates, has been shown to affect the epigenetic memory of an organism. Their long-term effects are unclear at this point, but many ongoing studies are attempting to elucidate the pathophysiological effects of such gene-environment interactions.
表观遗传学是指对基因的结构修饰,这种修饰不会改变核苷酸序列本身,而是控制和调节基因表达。DNA甲基化、组蛋白修饰和RNA调控是参与表观遗传修饰的一些机制。表观遗传变化被认为是生物体环境变化的结果,这种变化会导致大多数分化细胞发生固定和永久性的改变。一些与表观遗传变化有关的环境变化包括饥饿、叶酸和各种化学物质暴露。在生物体的生命周期中,存在一些时期,生物体特别容易受到表观遗传影响;这些时期包括受精、配子发生和早期胚胎发育。这些时期也是在女性生殖生命周期中进行干预以改善母婴健康的机会窗口。新数据表明,表观遗传影响可能参与胎儿发育的调节以及成人疾病如癌症、糖尿病、肥胖症和神经发育障碍的病理生理学过程。各种表观遗传机制也可能参与子痫前期和宫内生长受限的发病机制。此外,环境暴露被认为会导致表观遗传变化,进而引发疾病过程。接触重金属、生物类黄酮和内分泌干扰物,如双酚A和邻苯二甲酸盐,已被证明会影响生物体的表观遗传记忆。目前尚不清楚它们的长期影响,但许多正在进行的研究正试图阐明这种基因-环境相互作用的病理生理效应。