Sperm RNA Payload: Implications for Intergenerational Epigenetic Inheritance

There is mounting evidence that ancestral life experiences and environment can influence phenotypes in descendants. The parental environment regulates offspring phenotypes potentially via modulating epigenetic marks in the gametes. Here, we review examples of across-generational inheritance of paternal environmental effects and the current understanding of the role of small RNAs in such inheritance. We discuss recent advances in revealing the small RNA payload of sperm and how environmental conditions modulate sperm small RNAs. Further, we discuss the potential mechanism of inheritance of paternal environmental effects by focusing on sperm small RNA-mediated regulation of early embryonic gene expression and its role in influencing offspring phenotypes.