Desai M, Jellyman J K, Ross M G
1] Department of Obstetrics and Gynecology, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Perinatal Research Laboratories, Torrance, CA, USA [2] Department of Obstetrics and Gynecology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Int J Obes (Lond). 2015 Apr;39(4):633-41. doi: 10.1038/ijo.2015.13. Epub 2015 Feb 2.
Epigenetic mechanisms are emerging as mediators linking early environmental exposures during pregnancy with programmed changes in gene expression that alter offspring growth and development. There is irrefutable evidence from human and animal studies that nutrient and environmental agent exposures (for example, endocrine disruptors) during pregnancy may affect fetal/newborn development resulting in offspring obesity and obesity-associated metabolic abnormalities (metabolic syndrome). This concept of 'gestational programming' is associated with alterations to the epigenome (nongenomic) rather than changes in the DNA sequence (genomic). Epigenetic alterations induced by suboptimal maternal nutrition/endocrine factors include DNA methylation, histone modifications, chromatin remodeling and/or regulatory feedback by microRNAs, all of which have the ability to modulate gene expression and promote the metabolic syndrome phenotype. Recent studies have shown tissue-specific transcriptome patterns and phenotypes not only in the exposed individual, but also in subsequent progeny. Notably, the transmission of gestational programming effects to subsequent generations occurs in the absence of continued adverse environmental exposures, thus propagating the cycle of obesity and metabolic syndrome. This phenomenon may be attributed to an extrinsic process resulting from the maternal phenotype and the associated nutrient alterations occurring within each pregnancy. In addition, epigenetic inheritance may occur through somatic cells or through the germ line involving both maternal and paternal lineages. Since epigenetic gene modifications may be reversible, understanding how epigenetic mechanisms contribute to transgenerational transmission of obesity and metabolic dysfunction is crucial for the development of novel early detection and prevention strategies for programmed metabolic syndrome. In this review we discuss the evidence in human and animal studies for the role of epigenomic mechanisms in the transgenerational transmission of programmed obesity and metabolic syndrome.
表观遗传机制正逐渐成为一种介导因素，将孕期早期的环境暴露与基因表达的程序性变化联系起来，而这种变化会改变后代的生长和发育。来自人类和动物研究的证据确凿，孕期的营养和环境因素暴露（如内分泌干扰物）可能会影响胎儿/新生儿的发育，导致后代肥胖及与肥胖相关的代谢异常（代谢综合征）。这种“孕期编程”的概念与表观基因组（非基因组）的改变有关，而非DNA序列（基因组）的变化。由母体营养/内分泌因素欠佳所诱导的表观遗传改变包括DNA甲基化、组蛋白修饰、染色质重塑和/或微小RNA的调节反馈，所有这些都有能力调节基因表达并促进代谢综合征表型。最近的研究表明，不仅在暴露个体中，而且在其后代中都存在组织特异性转录组模式和表型。值得注意的是，孕期编程效应会在不存在持续不良环境暴露的情况下传递给后代，从而使肥胖和代谢综合征的循环持续下去。这种现象可能归因于由母体表型以及每次孕期内发生的相关营养改变所导致的外在过程。此外，表观遗传遗传可能通过体细胞或通过涉及母系和父系谱系的种系发生。由于表观遗传基因修饰可能是可逆的，了解表观遗传机制如何导致肥胖和代谢功能障碍的跨代传递，对于制定针对程序性代谢综合征的新型早期检测和预防策略至关重要。在这篇综述中，我们讨论了人类和动物研究中关于表观基因组机制在程序性肥胖和代谢综合征跨代传递中作用的证据。
