Sperm RNA code programmes the metabolic health of offspring


Mammalian sperm RNA is increasingly recognized as an additional source of paternal hereditary information beyond DNA. Environmental inputs, including an unhealthy diet, mental stresses and toxin exposure, can reshape the sperm RNA signature and induce offspring phenotypes that relate to paternal environmental stressors. Our understanding of the categories of sperm RNAs (such as tRNA-derived small RNAs, microRNAs, ribosomal RNA-derived small RNAs and long non-coding RNAs) and associated RNA modifications is expanding and has begun to reveal the functional diversity and information capacity of these molecules. However, the coding mechanism endowed by sperm RNA structures and by RNA interactions with DNA and other epigenetic factors remains unknown. How sperm RNA-encoded information is decoded in early embryos to control offspring phenotypes also remains unclear. Complete deciphering of the ‘sperm RNA code’ with regard to metabolic control could move the field towards translational applications and precision medicine, and this may lead to prevention of intergenerational transmission of obesity and type 2 diabetes mellitus susceptibility.

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Fig. 1: Information capacity and functional specificity of the sperm RNA code.
Fig. 2: Potential mechanisms in transformation of the sperm RNA code during embryo development.
Fig. 3: Future applications and precision medicine based on high resolution of sperm RNA code.


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The authors thank members of the Chen laboratory for extensive discussions on the manuscript. Y.Z. is supported by the Army Medical University (18JS008 and 2018XLC2018). F.T. is supported by the Institute of Genetics and Biophysics A. Buzzati-Traverso, C.N.R., Italy. M.R. is supported by La Fondation Nestlé France. Research in the Q.C. laboratory is supported by the NIH (R01HD092431).

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Nature Reviews Endocrinology thanks R. Barrès, M.-E. Patti and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Q.C., Y.Z. and J.S. developed the concept and wrote the manuscript. M.R. and F.T. provided a substantial contribution to discussion of the content, and reviewed and edited the manuscript before submission.

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Correspondence to Qi Chen.

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Zhang, Y., Shi, J., Rassoulzadegan, M. et al. Sperm RNA code programmes the metabolic health of offspring. Nat Rev Endocrinol 15, 489–498 (2019). https://doi.org/10.1038/s41574-019-0226-2

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