Small RNAs Are Trafficked from the Epididymis to Developing Mammalian Sperm

Sharma, Upasna; Sun, Fengyun; Conine, Colin C.; Reichholf, Brian; Kukreja, Shweta; Herzog, Veronika A.; Ameres, Stefan L.; Rando, Oliver J.

doi:10.1016/j.devcel.2018.06.023

Cited by 313 publications

(357 citation statements)

References 78 publications

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“…Temple‐Smith & Bedford, ) and eutherian mammals (e.g. Bedford, ; Baker et al ., ; Sullivan & Saez, ; Aalberts, Stout, & Stoorvogel, ; Skerget et al ., ; Machtinger, Laurent, & Baccarelli, ; Sharma et al ., ; Nixon et al ., ). Although less thoroughly studied, similar changes to sperm may occur within the Wolffian duct of reptiles (e.g.…”

Section: Elements Of the Life History Of Spermmentioning

confidence: 99%

Post‐ejaculatory modifications to sperm (PEMS)

Pitnick¹,

Wolfner

Dorus³

2019

Biological Reviews

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Mammalian sperm must spend a minimum period of time within a female reproductive tract to achieve the capacity to fertilize oocytes. This phenomenon, termed sperm ‘capacitation’, was discovered nearly seven decades ago and opened a window into the complexities of sperm–female interaction. Capacitation is most commonly used to refer to a specific combination of processes that are believed to be widespread in mammals and includes modifications to the sperm plasma membrane, elevation of intracellular cyclic AMP levels, induction of protein tyrosine phosphorylation, increased intracellular Ca2+ levels, hyperactivation of motility, and, eventually, the acrosome reaction. Capacitation is only one example of post‐ejaculatory modifications to sperm (PEMS) that are widespread throughout the animal kingdom. Although PEMS are less well studied in non‐mammalian taxa, they likely represent the rule rather than the exception in species with internal fertilization. These PEMS are diverse in form and collectively represent the outcome of selection fashioning complex maturational trajectories of sperm that include multiple, sequential phenotypes that are specialized for stage‐specific functionality within the female. In many cases, PEMS are critical for sperm to migrate successfully through the female reproductive tract, survive a protracted period of storage, reach the site of fertilization and/or achieve the capacity to fertilize eggs. We predict that PEMS will exhibit widespread phenotypic plasticity mediated by sperm–female interactions. The successful execution of PEMS thus has important implications for variation in fitness and the operation of post‐copulatory sexual selection. Furthermore, it may provide a widespread mechanism of reproductive isolation and the maintenance of species boundaries. Despite their possible ubiquity and importance, the investigation of PEMS has been largely descriptive, lacking any phylogenetic consideration with regard to divergence, and there have been no theoretical or empirical investigations of their evolutionary significance. Here, we (i) clarify PEMS‐related nomenclature; (ii) address the evolutionary origin, maintenance and divergence in PEMS in the context of the protracted life history of sperm and the complex, selective environment of the female reproductive tract; (iii) describe taxonomically widespread types of PEMS: sperm activation, chemotaxis and the dissociation of sperm conjugates; (iv) review the occurence of PEMS throughout the animal kingdom; (v) consider alternative hypotheses for the adaptive value of PEMS; (vi) speculate on the evolutionary implications of PEMS for genomic architecture, sexual selection, and reproductive isolation; and (vii) suggest fruitful directions for future functional and evolutionary analyses of PEMS.

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Section: Elements Of the Life History Of Spermmentioning

confidence: 99%

Post‐ejaculatory modifications to sperm (PEMS)

Pitnick¹,

Wolfner

Dorus³

2019

Biological Reviews

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“…It is gradually revealed that the substantial modifications in the sncRNA content in the spermatozoa is one of the major biological events during their epididymal transit (Nixon et al, 2015b;Chen et al, 2016a;Chu et al, 2017;Sharma et al, 2018). Additionally, the existence of piRNA sequences in the mature spermatozoa in the cauda epididymis is also quite intriguing.…”

Section: Progress Over the Past Decadementioning

confidence: 99%

“…In addition to the complex array of proteins and ions, mounting evidence suggests that the epididymal luminal environment contains different types of sncRNAs which are encapsulated and carried by the extracellular microvesicles known as the epididymosomes (Belleannee et al, 2013a;Sullivan & Saez, 2013;Nixon et al, 2015b). The existence of different sncRNAs, including miRNAs (Belleannee et al, 2013a;Reilly et al, 2016) and tsRNAs (Sharma et al, 2018) in the epididymosomes sheds light on the previously underappreciated function of epididymosome-mediated sperm sncRNA modification, through the mechanism similar to what was described for exosomal trafficking of miRNAs in nematodes, plants (Sarkies & Miska, 2014), and somatic cell contexts (Valadi et al, 2007;Gibbings et al, 2009;Zhang et al, 2015). Apart from the well-known function of facilitating the secretion of proteins that do not have a signal peptide (Cornwall, 2009), the epididymosomes are largely involved the exchange of sncRNAs between the epithelium and the spermatozoa.…”

Section: Progress Over the Past Decadementioning

confidence: 99%

“…Belonging to the family of exosomes, the epididymosomes are 40-100 nm highly heterogeneous vesicles secreted by the epididymal epithelial cells. Recently, by using a 'thiouracil tagging (TU)' mouse model (Gay et al, 2013) to trace the newly synthesized RNAs in the epididymis, which are captured and sequenced by the metabolic sequencing of RNA (SLAM-Seq) method (Herzog et al, 2017), it was further validated that the sncRNAs transferred to the spermatozoa via epididymosomes are indeed originally produced in the epididymal epithelium (Sharma et al, 2018). The existence of different sncRNAs, including miRNAs (Belleannee et al, 2013a;Reilly et al, 2016) and tsRNAs (Sharma et al, 2018) in the epididymosomes sheds light on the previously underappreciated function of epididymosome-mediated sperm sncRNA modification, through the mechanism similar to what was described for exosomal trafficking of miRNAs in nematodes, plants (Sarkies & Miska, 2014), and somatic cell contexts (Valadi et al, 2007;Gibbings et al, 2009;Zhang et al, 2015).…”

Section: Progress Over the Past Decadementioning

confidence: 99%

“…In addition to the in situ effects of regulating the expressions of target genes in the same epithelial cells, epididymal sncRNAs can be released into the epididymal lumen via epididymosomes which then fuse with other epithelial cells or the spermatozoa (Belleannee, 2015;Sharma et al, 2018). In the case of epididymal miRNAs, a subset of them are found to be selectively enriched in the epididymosomes, such as miR-202, miR-204, and miR-1224, compared with others that are predominantly localized in the surrounding epithelial cells (Belleannee, 2015).…”

Section: Progress Over the Past Decadementioning

confidence: 99%

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Epididymal small non‐coding RNA studies: progress over the past decade

Chu

Zhang

et al. 2019

Andrology

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Background: Small non-coding RNAs (sncRNAs) accomplish a huge variety of biological functions. Over the past decade, we have witnessed the substantial progress in the epididymal sncRNA studies. In the Epididymis 7, we had the true privilege of having a whole session to share our findings and exchange ideas on the epididymal sncRNA studies. Objectives: This mini-review attempts to provide an overview of what is known about the sncRNAs in the mammalian epididymis and discuss the future directions in this field. Methods: We surveyed literature regarding the sncRNA studies in the mammalian epididymis, and integrated some of our unpublished findings as well. We focus on the progress in methodology and the advances in our understanding of the expression and functions of epididymal sncRNAs. Results and Discussion: The applications of high-throughput approaches have made great contributions in the discovery of new sncRNA species and profiling their dynamics in the epithelial cells, the passing spermatozoa, and the luminal environment. The diverse classes of epididymal sncRNAs exert important biological functions from the in situ regulation of epididymal gene expression to the epigenetic inheritance in the offspring. Conclusion: Although still in its infancy, we believe that the research on epididymal sncRNAs will not only lead to a better understanding of their physiological and pathological functions, but also contribute to the whole landscape of the RNA field.

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Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

Cecere

2021

FEBS Letters

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Inherited information is transmitted to progeny primarily by the genome through the gametes. However, in recent years, epigenetic inheritance has been demonstrated in several organisms, including animals. Although it is clear that certain post-translational histone modifications, DNA methylation, and noncoding RNAs regulate epigenetic inheritance, the molecular mechanisms responsible for epigenetic inheritance are incompletely understood. This review focuses on the role of small RNAs in transmitting epigenetic information across generations in animals. Examples of documented cases of transgenerational epigenetic inheritance are discussed, from the silencing of transgenes to the inheritance of complex traits, such as fertility, stress responses, infections, and behavior. Experimental evidence supporting the idea that small RNAs are epigenetic molecules capable of transmitting traits across generations is highlighted, focusing on the mechanisms by which small RNAs achieve such a function. Just as the role of small RNAs in epigenetic processes is redefining the concept of inheritance, so too our understanding of the molecular pathways and mechanisms that govern epigenetic inheritance in animals is radically changing.

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Small RNAs Are Trafficked from the Epididymis to Developing Mammalian Sperm

Cited by 313 publications

References 78 publications

Post‐ejaculatory modifications to sperm (PEMS)

Post‐ejaculatory modifications to sperm (PEMS)

Epididymal small non‐coding RNA studies: progress over the past decade

Small RNAs in epigenetic inheritance: from mechanisms to trait transmission

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