Nutritonal Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, 48109-2029, USA.
Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI, 48109-2029, USA.
Curr Environ Health Rep. 2017 Dec;4(4):426-438. doi: 10.1007/s40572-017-0170-z.
The genetic material of every organism exists within the context of regulatory networks that govern gene expression-collectively called the epigenome. Animal models and human birth cohort studies have revealed key developmental periods that are important for epigenetic programming and vulnerable to environmental insults. Thus, epigenetics represent a potential mechanism through which sexually dimorphic effects of early-life exposures such as endocrine-disrupting chemicals (EDCs) manifest.
Several animal studies, and to a lesser extent human studies, have evaluated life-course sexually dimorphic health effects following developmental toxicant exposures; many fewer studies, however, have evaluated epigenetics as a mechanism mediating developmental exposures and later outcomes. To evaluate epigenetic reprogramming as a mechanistic link of sexually dimorphic early-life EDCs exposures, the following criteria should be met: (1) well-characterized exposure paradigm that includes relevant windows for developmental epigenetic reprogramming; (2) evaluation of sex-specific exposure-related epigenetic change; and (3) observation of a sexually dimorphic phenotype in either childhood, adolescence, or adulthood.
每个生物体的遗传物质都存在于调控基因表达的网络中，这些网络统称为表观基因组。动物模型和人类出生队列研究揭示了对表观遗传编程很重要且易受环境因素影响的关键发育阶段。因此，表观遗传学代表了一种潜在的机制，通过这种机制，早期生活暴露（如内分泌干扰物）的性别二态效应表现出来。
几项动物研究，在较小程度上还有人类研究，评估了发育毒物暴露后生命过程中性别二态健康效应；然而，评估作为发育暴露和后期结果中介的表观遗传学的研究要少得多。为了评估表观遗传重编程作为性别二态性早期生活内分泌干扰物暴露的机制联系，应满足以下标准：（1）特征明确的暴露范式，包括与发育性表观遗传重编程相关的相关窗口；（2）评估与性别特异性暴露相关的表观遗传变化；以及（3）在儿童期、青春期或成年期观察到性别二态表型。
