Epigenetic inheritance of acquired traits through sperm RNAs and sperm RNA modifications

Abstract

Once deemed heretical, emerging evidence now supports the notion that the inheritance of acquired characteristics can occur through ancestral exposures or experiences and that certain paternally acquired traits can be ‘memorized’ in the sperm as epigenetic information. The search for epigenetic factors in mammalian sperm that transmit acquired phenotypes has recently focused on RNAs and, more recently, RNA modifications. Here, we review insights that have been gained from studying sperm RNAs and RNA modifications, and their roles in influencing offspring phenotypes. We discuss the possible mechanisms by which sperm become acquisitive following environmental–somatic–germline interactions, and how they transmit paternally acquired phenotypes by shaping early embryonic development.

Transgenerational paternal transmission of acquired traits: stress-induced modification of the sperm regulatory transcriptome and offspring phenotypes

“…It is a sobering scientific lesson that Jean-Baptiste Lamarck’s evolutionary ideas should not have been dismissed out of hand, and that the hypotheses he generated should have been experimentally tested as soon as the appropriate tools became available. In fact, Charles Darwin was influenced by some of Lamarck’s ideas and presciently proposed the existence of ‘gemmules’ which he theorised were minute particles which could transfer information between somatic and germ cells via ‘pangenesis’ [for recent discussion see 62]. …”

Paternal and maternal urinary phthalate metabolite concentrations and birth weight of singletons conceived by subfertile couples

“…For example, there is new evidence to suggest that paternal environmental and lifestyle exposures may impact sperm epigenetics and consequently the health of offspring (Kumar et al 2013; Robinson et al 2012; Rando 2012; Chen et al 2016). Sperm contribute more than paternal genetic material to the oocyte, they also transmit oocyte activation factors, centrosomes, messenger RNA, and microRNA (Krawetz 2005; Kumar et al 2012).…”

tsRNAs: new players in mammalian retrotransposon control

“…In mammals such as mice, small RNA-mediated pathways centered by PIWI-interacting RNAs (piRNAs) are effective in controlling TE activities via post-transcriptional silencing or/and de novo methylation of TE loci [3]. However, piRNAs in mice are mostly expressed in the developing germ cells, but gradually depleted during sperm maturation and pre-implantation embryo development [4], leaving the question whether other small RNA pathways can silence TEs during this period of vulnerability. In a recent study published in Cell, Andrea et al [5] discovered that 3′-tRNAderived small RNAs (tsRNAs or tRFs) with different lengths (18 nt and 22 nt) can silence at least one class of mammalian TEs, the long terminal repeat (LTR)-retrotransposon, by blocking reverse transcription (RT; 18 nt) and post-transcriptional silencing (22 nt), respectively.…”

“…Could the reasons go beyond simply their sequences but extend to the specific RNA modifications harbored by each? It is known that modifications in tRNAs can dramatically change their secondary structures [6], and this may similarly apply to tsRNAs [4]. Indeed, the extra 4 nucleotides in 22-nt-3′-tRF harbor RNA modifications (Figure 1), which may contribute to altered RNA structure and interacting potential, possibly related to the recognition of ERV PBS and silencing complexes.…”

“…For example, tsRNAs are the most abundant small RNA species in the mature sperm of mice [4,7]. The sperm tsRNAs delivered at fertilization can change the transcriptome of pre-implantation embryo [8], including LTR-associated gene expression [9], and can generate longstanding effect that affect the phenotype of the offspring [8].…”