BACKGROUND Spermatogenesis generates a small and highly specialised type of cell that is apparently incapable of transcription and translation. For many years, this dogma was supported by the assumption that (i) the compact sperm nucleus, resulting from the substitution of histones by protamine during spermatogenesis, renders the genome inaccessible to the transcriptional machinery; and (ii) the loss of most organelles, including endoplasmic reticulum and ribosomes, limits or prevents translational activity. Despite these observations, several types of coding and non-coding RNAs have been identified in human sperm. Their functional roles, particularly during fertilisation and embryonic development, are only now becoming apparent. OBJECTIVE AND RATIONALE This review aimed to summarise current knowledge of the origin, types and functional roles of sperm RNAs, and to evaluate the clinical benefits of employing these transcripts as biomarkers of male fertility and reproductive outcomes. The possible contribution of sperm RNAs to intergenerational or transgenerational phenotypic inheritance is also addressed. SEARCH METHODS A comprehensive literature search on PubMed was conducted using the search terms ‘sperm’ AND ‘RNA’. Searches focussed upon articles written in English and published prior to August 2020. OUTCOMES The development of more sensitive and accurate RNA technologies, including RNA sequencing, has enabled the identification and characterisation of numerous transcripts in human sperm. Though a majority of these RNAs likely arise during spermatogenesis, other data support an epididymal origin of RNA transmitted to maturing sperm by extracellular vesicles. A minority may also be synthesised by de novo transcription in mature sperm, since a small portion of the sperm genome remains packed by histones. This complex RNA population has important roles in paternal chromatin packaging, sperm maturation and capacitation, fertilisation, early embryogenesis and developmental maintenance. In recent years, additional lines of evidence from animal models support a role for sperm RNAs in intergenerational or transgenerational inheritance, modulating both the genotype and phenotype of progeny. Importantly, several reports indicate that the sperm RNA content of fertile and infertile men differs considerably and is strongly modulated by the environment, lifestyle and pathological states. WIDER IMPLICATIONS Transcriptional profiling has considerable potential for the discovery of fertility biomarkers. Understanding the role of sperm transcripts and comparing the sperm RNA fingerprint of fertile and infertile men could help to elucidate the regulatory pathways contributing to male factor infertility. Such data might also provide a molecular explanation for several causes of idiopathic male fertility. Ultimately, transcriptional profiling may be employed to optimise ART procedures and overcome some of the underlying causes of male infertility, ensuring the birth of healthy children.

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关于精子 RNA 你需要知道的一切

背景技术精子发生产生一种小型且高度特化的细胞，其显然不能进行转录和翻译。多年来，这一教条得到以下假设的支持：(i) 精子发生过程中组蛋白被鱼精蛋白取代而导致的紧凑精子核导致转录机制无法进入基因组；(ii) 大多数细胞器的损失，包括内质网和核糖体，限制或阻止了翻译活动。尽管有这些观察结果，但已在人类精子中鉴定出几种类型的编码和非编码 RNA。它们的功能作用，特别是在受精和胚胎发育过程中，现在才变得明显。目的和理由 本综述旨在总结目前关于起源的知识，精子 RNA 的类型和功能作用，并评估使用这些转录物作为男性生育能力和生殖结果的生物标志物的临床益处。还讨论了精子 RNA 对代际或跨代表型遗传的可能贡献。搜索方法 使用搜索词“精子”和“RNA”对 PubMed 进行了全面的文献搜索。搜索的重点是用英文撰写并在 2020 年 8 月之前发表的文章。结果 包括 RNA 测序在内的更灵敏、更准确的 RNA 技术的发展，已经使人类精子中的大量转录本得以鉴定和表征。尽管这些 RNA 中的大多数可能在精子发生过程中出现，其他数据支持通过细胞外囊泡传递给成熟精子的 RNA 的附睾起源。少数也可以通过成熟精子中的从头转录合成，因为一小部分精子基因组仍然被组蛋白包裹。这种复杂的 RNA 群体在父系染色质包装、精子成熟和获能、受精、早期胚胎发生和发育维持中具有重要作用。近年来，来自动物模型的更多证据支持精子 RNA 在代际或跨代遗传中的作用，调节后代的基因型和表型。重要的是，一些报告表明，可育和不育男性的精子 RNA 含量差异很大，并且受环境、生活方式和病理状态的强烈调节。更广泛的意义 转录分析对于发现生育生物标志物具有相当大的潜力。了解精子转录本的作用并比较可育和不育男性的精子 RNA 指纹有助于阐明导致男性因素不育的调节途径。这些数据也可能为特发性男性生育力的几种原因提供分子解释。最终，转录分析可用于优化 ART 程序并克服男性不育的一些根本原因，确保健康儿童的出生。了解精子转录本的作用并比较可育和不育男性的精子 RNA 指纹有助于阐明导致男性因素不育的调节途径。这些数据也可能为特发性男性生育力的几种原因提供分子解释。最终，转录分析可用于优化 ART 程序并克服男性不育的一些根本原因，确保健康儿童的出生。了解精子转录本的作用并比较可育和不育男性的精子 RNA 指纹有助于阐明导致男性因素不育的调节途径。这些数据也可能为特发性男性生育力的几种原因提供分子解释。最终，转录分析可用于优化 ART 程序并克服男性不育的一些根本原因，确保健康儿童的出生。