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

Pang, Terence Y; Short, Annabel K.; Bredy, Timothy W.; Hannan, Anthony J.

doi:10.1016/j.cobeha.2017.02.007

Cited by 45 publications

(31 citation statements)

References 67 publications

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“…Such an approach not only confirmed a complex protein-coding RNA profile for sperm (i.e. mRNA transcripts ;Miller & Ostermeier 2006), but additionally documented, numerous species of non-protein-coding RNA, including numerous classes of sRNA (Ostermeier et al 2005, Krawetz et al 2011. Indeed, as documented earlier, the sRNAs that accumulate in mature spermatozoa include an abundance of miRNAs, endo-siRNAs, tRFs and piRNAs, as well as numerous additional sRNA molecules derived from the snRNA, snoRNA and rRNA molecules (Krawetz et al 2011, Song et al 2011, Peng et al 2012).…”

Section: Spermatozoa Harbour a Diverse Small Rna Profile That Is Potementioning

confidence: 72%

The contribution of epididymosomes to the sperm small RNA profile

2019

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It is now well established that mature spermatozoa harbour a rich and diverse profile of small non-protein-coding regulatory RNAs (sRNAs). There is also growing appreciation that this sRNA profile displays considerable plasticity, being altered in response to paternal exposure to a variety of environmental stressors. Coupled with evidence that upon delivery to the oocyte at the moment of fertilisation, sperm-borne sRNAs are able to influence both early embryonic development and the subsequent health of the offspring, there is now interest in both the timing and degree of change in the composition of the sRNA cargo of sperm. Models in which such epigenetic changes are linked to the spermatogenic cycle are seemingly incompatible with the lack of overt phenotypic changes in the spermatozoa of affected males. Rather, there is mounting consensus that such changes are imposed on sperm during their transit and storage within the epididymis, a protracted developmental window that takes place over several weeks. Notably, since spermatozoa are rendered transcriptionally and translationally silent during their development in the testes, it is most likely that the epididymis-documented alterations to the sperm sRNA profile are driven extrinsically, with a leading candidate being epididymosomes: small membrane enclosed extracellular vesicles that encapsulate a complex macromolecular cargo of proteins and RNAs, including the sRNAs. Here, we review the role of epididymosome–sperm communication in contributing to the establishment of the sperm sRNA profile during their epididymal transit.

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Section: Spermatozoa Harbour a Diverse Small Rna Profile That Is Potementioning

confidence: 72%

The contribution of epididymosomes to the sperm small RNA profile

2019

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“…higher anxiety, depression-like behaviours) across generations. Evidence from humans similarly links adverse paternal experiences to psychological stress disorders in the next generation (Pang et al 2017).…”

Section: Paternal Stressmentioning

confidence: 99%

Ejaculate-mediated paternal effects: evidence, mechanisms and evolutionary implications

et al. 2019

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Despite serving the primary objective of ensuring that at least one sperm cell reaches and fertilises an ovum, the male ejaculate (i.e. spermatozoa and seminal fluid) is a compositionally complex ‘trait’ that can respond phenotypically to subtle changes in conditions. In particular, recent research has shown that environmentally and genetically induced changes to ejaculates can have implications for offspring traits that are independent of the DNA sequence encoded into the sperm’s haploid genome. In this review, we compile evidence from several disciplines and numerous taxonomic systems to reveal the extent of such ejaculate-mediated paternal effects (EMPEs). We consider a number of environmental and genetic factors that have been shown to impact offspring phenotypes via ejaculates, and where possible, we highlight the putative mechanistic pathways by which ejaculates can act as conduits for paternal effects. We also highlight how females themselves can influence EMPEs, and in some cases, how maternally derived sources of variance may confound attempts to test for EMPEs. Finally, we consider a range of putative evolutionary implications of EMPEs and suggest a number of potentially useful approaches for exploring these further. Overall, our review confirms that EMPEs are both widespread and varied in their effects, although studies reporting their evolutionary effects are still in their infancy.

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“…If this paradigm was to hold across other forms of stress, it would imply that the physiology of the epididymal epithelial cells is likely being altered, and that this change in the cellular environment is capable of influencing the selective packaging of sRNA species that differ from those packaged under normal physiological conditions. While not widely studied, this possibility has been considered in the context of chronic stress, wherein exposure to elevated corticosterone elicits a cascade of responses including aberrant expression of the glucocorticoid receptor and epididymal epithelial cell signaling, putatively resulting in equivalent changes to the sperm sRNA profile (Pang et al ., ).…”

Section: Mechanisms Responsible For Remodeling Of the Srna Profile Ofmentioning

confidence: 97%

“…The resulting alterations in the sperm sRNA profile were linked to behavioral phenotypes displayed by the resulting offspring, with causality of these responses being demonstrated by microinjection of total RNA from the spermatozoa of traumatized male mice into fertilized oocytes, a strategy that recapitulated the offspring phenotype (Gapp et al ., ). Subsequent examination of this paradigm has confirmed that a diversity of paternal stressors [including dietary perturbation (de Castro Barbosa et al ., ; Chen et al ., ,b; Fullston et al ., ; McPherson et al ., ; Sharma et al ., ), psychological stress (Rodgers et al ., ; Saavedra‐Rodriguez & Feig, ; Pang et al ., ; Dickson et al ., ), ethanol consumption (Rompala et al ., ), environmental toxicants (Metzler‐Guillemain et al ., ; Paris et al ., ) and cigarette smoke exposure (Marczylo et al ., ), and even exercise (Short et al ., ; Ingerslev et al ., )] can each differentially alter the sRNA profile of effected males as well as to contribute to overt phenotypic disturbances in their offspring. Among these studies, a handful have specifically sought to examine the mechanisms by which the sperm sRNA profile is altered and provided additional evidence of the pivotal role played by epididymosomes.…”

Section: Mechanisms Responsible For Remodeling Of the Srna Profile Ofmentioning

confidence: 99%

Profiling of epididymal small non‐protein‐coding RNAs

et al. 2019

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Background: Our understanding of epididymal physiology and function has been transformed over the three decades in which the International Meeting Series on the Epididymis has been hosted. This transformation has occurred along many fronts, but among the most significant advances has been the unexpected discovery of the diversity of small non-protein-coding RNAs (sRNAs) expressed in the epididymal epithelium and differentially accumulated in the luminal population of spermatozoa. Objectives: Here we survey recent literature pertaining to profiling the sRNA landscape of the mammalian epididymis with the goal of demonstrating the contribution that these key regulatory elements, and their associated pathways, make to epididymal physiology and sperm maturation. Results and discussion: High throughput sequencing strategies have fueled an unprecedented advance in our understanding of RNA biology. In the last decade, such high throughput profiling tools have been increasingly applied to study the mammalian epididymis, presaging the discovery of diverse classes of sRNA expressed along the length of the tract. Among the best studied sRNA classes are the microRNAs (miRNA), a sRNA species shown to act in concert with endocrine signals to fine-tune the segmental patterning of epididymal gene expression. In addition to performing this homeostatic role, epithelial cell-derived sRNAs also selectively accumulate into the epididymosomes and spermatozoa that occupy the duct lumen. This exciting discovery alludes to a novel form of intracellular communication that contributes to the establishment of the sperm epigenome and its modification under conditions of paternal stress. Conclusion: Compelling literature has identified sRNAs as a crucial regulatory tier that allows the epididymis to fulfill its combined roles of sperm transport, maturation, and storage. Continued research in this emerging field will contribute to our growing understanding of the etiology of male factor infertility and potentially allow for the future design of rational therapeutic options for these individuals.

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

Cited by 45 publications

References 67 publications

The contribution of epididymosomes to the sperm small RNA profile

The contribution of epididymosomes to the sperm small RNA profile

Ejaculate-mediated paternal effects: evidence, mechanisms and evolutionary implications

Profiling of epididymal small non‐protein‐coding RNAs

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