Background

An organism's metabolic phenotype is primarily affected by its genotype, its lifestyle, and the nutritional composition of its food supply. In addition, it is now clear from studies in many different species that ancestral environments can also modulate metabolism in at least one to two generations of offspring.

Scope of review

We limit ourselves here to paternal effects in mammals, primarily focusing on studies performed in inbred rodent models. Although hundreds of studies link paternal diets and offspring metabolism, the mechanistic basis by which epigenetic information in sperm programs nutrient handling in the next generation remains mysterious. Our goal in this review is to provide a brief overview of paternal effect paradigms and the germline epigenome. We then pivot to exploring one key mystery in this literature: how do epigenetic changes in sperm, most of which are likely to act transiently in the early embryo, ultimately direct a long-lasting physiological response in offspring?

Major conclusions

Several potential mechanisms exist by which transient epigenetic modifications, such as small RNAs or methylation states erased shortly after fertilization, could be transferred to more durable heritable information. A detailed mechanistic understanding of this process will provide deep insights into early development, and could be of great relevance for human health and disease.

中文翻译：

---

早期生活教训：种系表观遗传信息对有机体发育的持久影响。

背景

生物体的代谢表型主要受其基因型、生活方式和食物供应的营养成分的影响。此外，现在从许多不同物种的研究中可以清楚地看出，祖先环境也可以调节至少一到两代后代的新陈代谢。

审查范围

我们在这里将自己局限于哺乳动物的父系效应，主要关注近交啮齿动物模型中进行的研究。尽管数百项研究将父亲的饮食和后代的新陈代谢联系起来，但精子中的表观遗传信息规划下一代营养处理的机制基础仍然是个谜。我们在这篇综述中的目标是提供父本效应范式和种系表观基因组的简要概述。然后，我们转向探索该文献中的一个关键谜团：精子的表观遗传变化（其中大多数可能在早期胚胎中短暂发挥作用）如何最终指导后代产生持久的生理反应？

主要结论

存在几种潜在的机制，通过这些机制，短暂的表观遗传修饰（例如受精后不久消除的小RNA或甲基化状态）可以转移为更持久的遗传信息。对这一过程的详细机制理解将为早期发育提供深入的见解，并且可能与人类健康和疾病密切相关。