Kretschmer Miriam, Gapp Katharina
Department of Health Sciences and Technology, ETH Zurich, Laboratory of Molecular and Behavioral Neuroscience, Institute for Neuroscience, Winterthurerstrasse 190, Zurich 8057, Switzerland.
Environ Epigenet. 2022 Apr 16;8(1):dvac011. doi: 10.1093/eep/dvac011. eCollection 2022.
The inheritance of neurophysiologic and neuropsychologic complex diseases can only partly be explained by the Mendelian concept of genetic inheritance. Previous research showed that both psychological disorders like post-traumatic stress disorder and metabolic diseases are more prevalent in the progeny of affected parents. This could suggest an epigenetic mode of transmission. Human studies give first insight into the scope of intergenerational influence of stressors but are limited in exploring the underlying mechanisms. Animal models have elucidated the mechanistic underpinnings of epigenetic transmission. In this review, we summarize progress on the mechanisms of paternal intergenerational transmission by means of sperm RNA in mouse models. We discuss relevant details for the modelling of RNA-mediated transmission, point towards currently unanswered questions and propose experimental considerations for tackling these questions.
神经生理和神经心理复杂疾病的遗传仅部分能用孟德尔遗传概念来解释。先前的研究表明，诸如创伤后应激障碍等心理障碍和代谢疾病在患病父母的后代中更为普遍。这可能暗示了一种表观遗传的传递模式。人体研究初步揭示了应激源的代际影响范围，但在探索潜在机制方面存在局限性。动物模型已经阐明了表观遗传传递的机制基础。在这篇综述中，我们总结了小鼠模型中精子RNA介导的父系代际传递机制的研究进展。我们讨论了RNA介导传递模型的相关细节，指出了目前尚未解决的问题，并提出了解决这些问题的实验思路。
