Abstract
The most fundamental process for the perpetuation of a species is the transfer of information from parent to offspring. Although genomic DNA contributes to the majority of the inheritance, it is now clear that epigenetic information −information beyond the underlying DNA sequence − is also passed on to future generations. However, the mechanism and extent of such inheritance are not well-understood. Here, I review some of the concepts, evidence, and mechanisms of intergenerational epigenetic inheritance via sperm small RNAs. Recent studies provide evidence that mature sperm are highly abundant in small non-coding RNAs. These RNAs are modulated by paternal environmental conditions and potentially delivered to the zygote at fertilization, where they can regulate early embryonic development. Intriguingly, sperm small RNA payload undergoes dramatic changes during testicular and post-testicular maturation, making the mature sperm epigenome highly unique and distinct from testicular germ cells. I explore the mechanism of sperm small RNA remodeling during post-testicular maturation in the epididymis, and the potential role of this reprograming in intergenerational epigenetic inheritance.
Highlights
The possibility that our life experiences can influence phenotypes in our descendants has tremendous implications for basic biology and public health and policy (Jirtle and Skinner, 2007)
This study provided the first direct evidence that paternal environmental information is transmitted by sperm RNAs, and identified a specific set of micro RNAs (miRNAs) that change in MSUS sperm in response to stress (Gapp et al, 2014)
Microinjection of a synthetic 5 fragment of tRNA-GlyGCC or an inhibitor of tRFGlyGCC −among the most abundant small RNAs in sperm, which is up-regulated in low protein sperm− in control zygotes revealed that tRFGlyGCC represses transcription of a specific set of MERVL retroviral element-driven genes in early embryos (Sharma et al, 2016)
Summary
The possibility that our life experiences can influence phenotypes in our descendants has tremendous implications for basic biology and public health and policy (Jirtle and Skinner, 2007). Numerous studies provide evidence that paternal environmental conditions, such as altered diet or stress, influence small RNA levels in sperm, the mechanistic understanding of how any of the environmental exposures noted above cause specific changes in sperm small RNA levels is largely lacking.
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