Ross Pablo Juan, Canovas Sebastian
Department of Animal Science, University of California, Davis, CA 95616 USA.
LARCEL (Laboratorio Andaluz de Reprogramación Celular), BIONAND, Centro Andaluz de Nanomedicina y Biotecnología Campanillas, Malaga 29590, Spain.
Reprod Fertil Dev. 2016;28(1-2):25-40. doi: 10.1071/RD15365.
Epigenetics involves mechanisms independent of modifications in the DNA sequence that result in changes in gene expression and are maintained through cell divisions. Because all cells in the organism contain the same genetic blueprint, epigenetics allows for cells to assume different phenotypes and maintain them upon cell replication. As such, during the life cycle, there are moments in which the epigenetic information needs to be reset for the initiation of a new organism. In mammals, the resetting of epigenetic marks occurs at two different moments, which both happen to be during gestation, and include primordial germ cells (PGCs) and early preimplantation embryos. Because epigenetic information is reversible and sensitive to environmental changes, it is probably no coincidence that both these extensive periods of epigenetic remodelling happen in the female reproductive tract, under a finely controlled maternal environment. It is becoming evident that perturbations during the extensive epigenetic remodelling in PGCs and embryos can lead to permanent and inheritable changes to the epigenome that can result in long-term changes to the offspring derived from them, as indicated by the Developmental Origins of Health and Disease (DOHaD) hypothesis and recent demonstration of inter- and trans-generational epigenetic alterations. In this context, an understanding of the mechanisms of epigenetic remodelling during early embryo development is important to assess the potential for gametic epigenetic mutations to contribute to the offspring and for new epimutations to be established during embryo manipulations that could affect a large number of cells in the offspring. It is of particular interest to understand whether and how epigenetic information can be passed on from the gametes to the embryo or offspring, and whether abnormalities in this process could lead to transgenerationally inheritable phenotypes. The aim of this review is to highlight recent progress made in understanding the nature and mechanisms of epigenetic remodelling that ensue after fertilisation.
表观遗传学涉及独立于DNA序列修饰的机制，这些机制导致基因表达发生变化，并在细胞分裂过程中得以维持。由于生物体中的所有细胞都包含相同的遗传蓝图，表观遗传学使得细胞能够呈现不同的表型，并在细胞复制时保持这些表型。因此，在生命周期中，存在表观遗传信息需要重置以启动新生物体的时刻。在哺乳动物中，表观遗传标记的重置发生在两个不同的时刻，这两个时刻恰好都在妊娠期，包括原始生殖细胞（PGC）和早期植入前胚胎。由于表观遗传信息是可逆的且对环境变化敏感，这两个广泛的表观遗传重塑时期都发生在女性生殖道中，处于精细控制的母体环境下，这可能并非巧合。越来越明显的是，PGC和胚胎中广泛的表观遗传重塑过程中的扰动会导致表观基因组发生永久性和可遗传的变化，从而导致源自它们的后代出现长期变化，正如健康与疾病发育起源（DOHaD）假说以及近期对代际和跨代表观遗传改变的研究所表明的那样。在这种背景下，了解早期胚胎发育过程中的表观遗传重塑机制对于评估配子表观基因突变对后代的潜在影响以及在可能影响后代大量细胞的胚胎操作过程中建立新的表观突变至关重要。特别令人感兴趣的是了解表观遗传信息是否以及如何从配子传递给胚胎或后代，以及这个过程中的异常是否会导致跨代可遗传的表型。本综述的目的是突出在理解受精后表观遗传重塑的本质和机制方面取得的最新进展。
