Sperm RNA as a Mediator of Genomic Plasticity

Figure 4

Schematic for sperm RNA-mediated transgenerational inheritance. Cartoon depicting possible modifications in sperm RNA content (yellow bars) over background (black bars) in relation to behavioral changes in male F1 and F2 mice from litters subjected to separation trauma based on maternal separation combined with unpredictable maternal stress (MSUS). Alterations in behaviour in response to the stressor must be neurological in origin and for transmission to the F1s derived from those males neurological changes must somehow be signaled to gametes. Evidence presented by Gapp et al. [120] suggests that the signal could be transmitted in the circulation to the male reproductive system by miRNAs or their precursors. One testable hypothesis is that the sperm-derived RNA signal may only be required for F0 (stress exposed) to F1 transgenerational transmission before becoming imprinted in the DNA epigenome (CH₃ groups in sperm cartoon) in the F1 zygote and hence transmitted by sperm DNA into the F2 and subsequent generations; this RNA-mediated effect could equally, however, involve demethylation. In this author’s view, miRNAs may not be required to traverse the blood testis barrier if they first encounter mature sperm passing through the epididymis via exosomes, adapted from Gapp et al, 2014.