Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology/Pneumology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.
Institute of Pharmacy, Freie Universität Berlin, Berlin, Germany.
Am J Physiol Cell Physiol. 2024 Sep 1;327(3):C750-C777. doi: 10.1152/ajpcell.00359.2024. Epub 2024 Jul 16.
Parental genes can influence the phenotype of their offspring through genomic-epigenomic interactions even without the direct inheritance of specific parental genotypes. Maternal genetic variations can affect the ovarian and intrauterine environments and potentially alter lactation behaviors, impacting offspring nutrition and health outcomes independently of the fetal genome. Similarly, paternal genetic changes can affect the endocrine system and vascular functions in the testes, influencing sperm quality and seminal fluid composition. These changes can initiate early epigenetic modifications in sperm, including alterations in microRNAs, tRNA-derived small RNAs (tsRNAs), and DNA methylation patterns. These epigenetic modifications might induce further changes in target organs of the offspring, leading to modified gene expression and phenotypic outcomes without transmitting the original parental genetic alterations. This review presents clinical evidence supporting this hypothesis and discusses the potential underlying molecular mechanisms. Parental gene-offspring epigenome-offspring phenotype interactions have been observed in neurocognitive disorders and cardio-renal diseases.
父母的基因可以通过基因组-表观基因组相互作用影响后代的表型，即使没有特定父母基因型的直接遗传。母体遗传变异可以影响卵巢和子宫内环境，并可能改变哺乳行为，从而影响后代的营养和健康结果，而与胎儿基因组无关。同样，父系遗传变化会影响睾丸中的内分泌系统和血管功能，影响精子质量和精液成分。这些变化可以在精子中引发早期的表观遗传修饰，包括 microRNAs、tRNA 衍生的小 RNA（tsRNAs）和 DNA 甲基化模式的改变。这些表观遗传修饰可能会在后代的靶器官中引发进一步的变化，导致基因表达和表型结果的改变，而不会传递原始的父母遗传改变。这篇综述介绍了支持这一假说的临床证据，并讨论了潜在的分子机制。在神经认知障碍和心肾疾病中已经观察到了父母基因-后代表观基因组-后代表型的相互作用。
