德国环境卫生研究中心R. Teperino团队近期取得重要工作进展，他们研究报导了饮食诱导和精子携带的线粒体RNA的表观遗传。相关研究成果2024年6月5日在线发表于《自然》杂志上。

据介绍，精子含有一个复杂的、对环境敏感的小型非编码RNA（sncRNA）库，影响后代的发育和成年表型。附睾中的精子是否对环境因素直接敏感尚不完全清楚。

研究人员使用了两种不同的孕前急性高脂肪饮食模式来分析附睾和睾丸对精子sncRNA库和后代健康的贡献。研究发现，附睾精子（而不是发育中的生殖细胞）对环境敏感，研究人员将线粒体tRNA（mt-tRNA）及其片段（mt-tsRNA）鉴定为精子传播因子。在人类中，精子中的mt-tsRNA与体重指数相关，而父亲在受孕时超重会使后代肥胖风险翻倍，并损害代谢健康。

参与线粒体功能的基因突变小鼠的精子sncRNA测序及其野生型后代的代谢表型表明，mt-tsRNA的上调是线粒体功能障碍的下游。遗传杂交双细胞胚胎的单胚胎转录组学证明，受精时mt-tRNA的精子到卵母细胞的转移，并表明它们参与了早期胚胎转录的调控。

总之，这一研究支持了父亲在受孕时的健康对后代代谢的重要性，表明mt-tRNA是由饮食诱导和精子传播的，并证明在生理环境中，精子线粒体RNA在受精时由父亲传递给后代。

附：英文原文

Title: Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs

Author: Tomar, A., Gomez-Velazquez, M., Gerlini, R., Comas-Armangu, G., Makharadze, L., Kolbe, T., Boersma, A., Dahlhoff, M., Burgstaller, J. P., Lassi, M., Darr, J., Toppari, J., Virtanen, H., Khnapfel, A., Scholz, M., Landgraf, K., Kiess, W., Vogel, M., Gailus-Durner, V., Fuchs, H., Marschall, S., Hrab de Angelis, M., Kotaja, N., Krner, A., Teperino, R.

Issue&Volume: 2024-06-05

Abstract: Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1,2,3,4,5,6,7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

DOI: 10.1038/s41586-024-07472-3

Source: https://www.nature.com/articles/s41586-024-07472-3