Priority Research Centre for Reproductive Science, School of Environmental and Life Sciences, The University of Newcastle, Callaghan, New South Wales, Australia.
Hunter Medical Research Institute, New Lambton Heights, New South Wales, Australia.
Reproduction. 2019 Jun;157(6):R209-R223. doi: 10.1530/REP-18-0480.
It is now well established that mature spermatozoa harbour a rich and diverse profile of small non-protein-coding regulatory RNAs (sRNAs). There is also growing appreciation that this sRNA profile displays considerable plasticity, being altered in response to paternal exposure to a variety of environmental stressors. Coupled with evidence that upon delivery to the oocyte at the moment of fertilisation, sperm-borne sRNAs are able to influence both early embryonic development and the subsequent health of the offspring, there is now interest in both the timing and degree of change in the composition of the sRNA cargo of sperm. Models in which such epigenetic changes are linked to the spermatogenic cycle are seemingly incompatible with the lack of overt phenotypic changes in the spermatozoa of affected males. Rather, there is mounting consensus that such changes are imposed on sperm during their transit and storage within the epididymis, a protracted developmental window that takes place over several weeks. Notably, since spermatozoa are rendered transcriptionally and translationally silent during their development in the testes, it is most likely that the epididymis-documented alterations to the sperm sRNA profile are driven extrinsically, with a leading candidate being epididymosomes: small membrane enclosed extracellular vesicles that encapsulate a complex macromolecular cargo of proteins and RNAs, including the sRNAs. Here, we review the role of epididymosome-sperm communication in contributing to the establishment of the sperm sRNA profile during their epididymal transit.
现在已经证实，成熟的精子中含有丰富多样的小非蛋白编码调控 RNA（sRNA）。越来越多的证据表明，这种 sRNA 谱具有相当大的可塑性，能够响应父代暴露于各种环境应激源而发生改变。此外，有证据表明，在受精时，精子携带的 sRNA 能够影响早期胚胎发育和后代的后续健康，因此人们对精子 sRNA 货物的组成在时间和程度上的变化都产生了兴趣。与精子发生周期相关的这种表观遗传变化的模型与受影响男性的精子明显没有表型变化似乎是不相容的。相反，越来越多的共识认为，这种变化是在精子在附睾中的运输和储存过程中施加的，这是一个长达数周的延长发育窗口。值得注意的是，由于精子在睾丸中的发育过程中是转录和翻译沉默的，因此最有可能的是，附睾中记录的精子 sRNA 谱的改变是由外在因素驱动的，其中一个主要候选者是附睾小体：小的膜包裹的细胞外囊泡，其中包含蛋白质和 RNA 等复杂的大分子货物，包括 sRNA。在这里，我们综述了附睾小体与精子之间的通讯在精子在附睾中的运输过程中建立精子 sRNA 谱中的作用。
