Belton Christian, Kelsey Gavin
Epigenetics Programme, The Babraham Institute, Cambridge, UK.
Loke Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
Epigenomics. 2025 Jul 3:1-9. doi: 10.1080/17501911.2025.2525749.
Experimental models and epidemiological data suggest that environmental factors, for example, adverse nutrition prior to conception, can lead to phenotypes in offspring of exposed parents in the absence of continued exposure. As a result these phenotypes have been described as epigentically inherited. The mechanistic basis for such phenomena has not been established in most cases. In this review, we consider possible contributing mechanisms for environmentaly induced epigenetic inheritance, with a focus on maternally transmitted effects and by comparing to paradigms of epigenetic inheritance with a clear mechanistic understanding. Genomic imprinting has provided an important conceptual framework for how the epigenetic states of parental germlines can determine allelic expression in offspring, yet, generally speaking, imprinted genes appear resilient to epigenetic disruption from altered parental environments. Metastable epialleles are environmentally sensitive and variably expressed loci that can impact organism phenotype, but the nature of any epigenetic marker at these loci transferred to offspring is unclear. Studies of examples across these forms of epigenetic inheritance show predominant effects are mediated by oocyte factors involved inreprogramming of the genome post-fertilization, rather than direct effects on gametic DNA methylation, with the exception of genomic imprinting. The potential contribution of additional oocyte chromatin features to the specific liability of phenotypic effector genes and their potential to persist through this reprogramming, however, remains to be investigated.
实验模型和流行病学数据表明，环境因素，例如受孕前的不良营养状况，在没有持续接触的情况下，可导致暴露父母的后代出现特定表型。因此，这些表型被描述为表观遗传。在大多数情况下，此类现象的机制基础尚未确立。在本综述中，我们探讨了环境诱导表观遗传的可能机制，重点关注母系遗传效应，并与具有明确机制理解的表观遗传范例进行比较。基因组印记为亲代生殖系的表观遗传状态如何决定后代等位基因表达提供了重要的概念框架，然而，一般来说，印记基因似乎对亲代环境改变引起的表观遗传破坏具有抗性。亚稳定表观等位基因是对环境敏感且表达可变的位点，可影响生物体表型，但这些位点转移至后代的任何表观遗传标记的性质尚不清楚。对这些表观遗传形式的实例研究表明，除基因组印记外，主要影响是由受精后参与基因组重编程的卵母细胞因子介导的，而非对配子DNA甲基化的直接影响。然而，卵母细胞染色质的其他特征对表型效应基因的特定易感性及其在这种重编程过程中持续存在的可能性的潜在贡献仍有待研究。
