Sperm RNA-mediated epigenetic inheritance in mammals: challenges and opportunities

Emerging evidence now shows that in addition to delivering a haploid DNA, the mammalian sperm also carry various types of RNAs that respond to the paternal environment, which can mediate the intergenerational transmission of certain phenotypes to the offspring relating to the paternal environmental exposures (e.g. diet, mental stress). Improved analytical tools are beginning to decipher the complexity of sperm RNAs, RNA modifications and their spatial compartmentalisation, which support the concept of 'sperm RNA code' in programming specific offspring phenotypes during embryonic development. In this commentary article, I discuss the challenges and opportunities in solidifying the field of mammalian sperm RNA-mediated epigenetic inheritance, including the identification of the key sperm RNAs that are responsible for the paternal phenotype transmission, and the cellular and molecular events that are triggered by sperm RNAs during embryo development. I also discuss the translational application potential by harnessing the knowledge of sperm RNA code to improve farm animal production and human health.