Paternal epigenetics: Mammalian sperm provide much more than DNA at fertilization

Blévec, Emilie Le; Muroňová, Jana; Ray, Pierre F.; Arnoult, Christophe

doi:10.1016/j.mce.2020.110964

Cited by 53 publications

(36 citation statements)

References 189 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, bta-miR-100, one highly expressed miRNA in ejaculated sperm, has been proposed as one of the main factors associated with the initiation of pluripotency [ 69 , 70 ] and bta-miR-191, the second most expressed miRNA in our dataset has been associated with fertilization rate and embryo quality in humans [ 71 ]. Likewise, miRNA-34c is known to enhance the germinal phenotype of cells already committed to this lineage during spermatogenesis [ 6 ], but is also a key player in murine early embryo development [ 72 – 74 ]. In addition, clusters 10–12 were found to be associated with GO terms related to embryo development such as developmental process, embryonic morphogenesis, as well as cell proliferation, differentiation, and migration.…”

Section: Discussionmentioning

confidence: 99%

Dynamics of cattle sperm sncRNAs during maturation, from testis to ejaculated sperm

Sellem¹,

Marthey

Rau

et al. 2021

Epigenetics & Chromatin

View full text Add to dashboard Cite

Background During epididymal transit, spermatozoa go through several functional maturation steps, resulting from interactions with epididymal secretomes specific to each region. In particular, the sperm membrane is under constant remodeling, with sequential attachment and shedding of various molecules provided by the epididymal lumen fluid and epididymosomes, which also deliver sncRNA cargo to sperm. As a result, the payload of sperm sncRNAs changes during the transit from the epididymis caput to the cauda. This work was designed to study the dynamics of cattle sperm sncRNAs from spermatogenesis to final maturation. Results Comprehensive catalogues of sperm sncRNAs were obtained from testicular parenchyma, epididymal caput, corpus and cauda, as well as ejaculated semen from three Holstein bulls. The primary cattle sncRNA sperm content is markedly remodeled as sperm mature along the epididymis. Expression of piRNAs, which are abundant in testis parenchyma, decreases dramatically at epididymis. Conversely, sperm progressively acquires miRNAs, rsRNAs, and tsRNAs along epididymis, with regional specificities. For instance, miRNAs and tsRNAs are enriched in epididymis cauda and ejaculated sperm, while rsRNA expression peaks at epididymis corpus. In addition, epididymis corpus contains mainly 20 nt long piRNAs, instead of 30 nt in all other locations. Beyond the bulk differences in abundance of sncRNAs classes, K-means clustering was performed to study their spatiotemporal expression profile, highlighting differences in specific sncRNAs and providing insights into their putative biological role at each maturation stage. For instance, Gene Ontology analyses using miRNA targets highlighted enriched processes such as cell cycle regulation, response to stress and ubiquitination processes in testicular parenchyma, protein metabolism in epididymal sperm, and embryonic morphogenesis in ejaculated sperm. Conclusions Our findings confirm that the sperm sncRNAome does not simply reflect a legacy of spermatogenesis. Instead, sperm sncRNA expression shows a remarkable level of plasticity resulting probably from the combination of multiple factors such as loss of the cytoplasmic droplet, interaction with epididymosomes, and more surprisingly, the putative in situ production and/or modification of sncRNAs by sperm. Given the suggested role of sncRNA in epigenetic trans-generational inheritance, our detailed spatiotemporal analysis may pave the way for a study of sperm sncRNAs role in embryo development.

show abstract

Section: Discussionmentioning

confidence: 99%

Dynamics of cattle sperm sncRNAs during maturation, from testis to ejaculated sperm

Sellem¹,

Marthey

Rau

et al. 2021

Epigenetics & Chromatin

View full text Add to dashboard Cite

show abstract

“…Moreover, epigenetic defects of the sperm could induce decreased developmental capacity of the generated embryos, providing a possible explanation for early pregnancy loss ( Stuppia et al, 2015 ). Considering the growing evidence on male contribution to embryo development and involvement of gene regulators such as histone modifications and small non-coding RNAs ( Baxter and Drake, 2019 ; Le Blévec et al, 2020 ), this emerging field of study deserves further research in domestic species, particularly in relation to biotechnologies applied for increasing reproductive efficiency.…”

Section: Discussionmentioning

confidence: 99%

Desmosterol Incorporation Into Ram Sperm Membrane Before Cryopreservation Improves in vitro and in vivo Fertility

Carro

Ramírez-Vasquez

Peñalva

et al. 2021

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Pregnancy rates in ewes are markedly low after cervical insemination with frozen-thawed sperm. Sensitivity of ram sperm to freeze-thawing is related to the lipid composition of the membrane, particularly to its low sterol content. Recently, we proved that sterol content of ram sperm can be increased by treatment with methyl-β-cyclodextrin-sterol complexes and we provided mechanistic based evidence on the differential behavior of cholesterol and desmosterol in the ram sperm membrane. In the present study, we evaluated the role of increasing cholesterol and desmosterol content of ram sperm before cryopreservation, on the extent and distribution of sterols, cryocapacitation status, acrosome integrity, DNA damage associated with apoptosis and fertility competence in vitro and in vivo of post-thawed sperm. After freeze-thawing, similar levels of sterol content were evidenced in control sperm cells and in those pre-incubated with either cholesterol or desmosterol. Still, moderately higher levels of sterols were registered in treated sperm compared to the control, indicating no physiological excess of sterols after thawing or sterol losses that exceed the control. Live cell imaging of fluorescent cholesterol evidenced the presence of sperm sub-populations differentially affected by freeze-thawing. Similar unimodal frequency profiles were observed between sterol-enriched groups, while the control exhibited a sub-population of sperm compatible with low sterol content. Tyrosine phosphorylation was significantly lower when ram sperm incorporated cholesterol compared to the control. No difference in this capacitation parameter was found between the latter and desmosterol-enriched sperm. The percentage of sperm with damaged acrosomes post-thawing, assessed by a fluorescent lectin, was reduced in sperm that incorporated sterols before freezing, irrespective of the sterol class. These results suggest that sterols exert a stabilizing effect on the acrosome. No differences were found in levels of apoptotic DNA fragmentation among experimental groups. As to fertility trials, desmosterol-enriched sperm gave rise to higher rates of in vitro activated oocytes by heterologous fertilization and to significantly lower pregnancy loss in vivo. Our research provides new insights on sterol incorporation into ram sperm prior to cryopreservation, in particular on the additional benefit of incorporating desmosterol as a strategy to improve fertility outcome.

show abstract

“…In short, epigenetic modifications regulate gene expression without altering nucleotide sequence. Epigenetic modulations include DNA methylation, histone tail post-translational modifications (PTMs), and non-coding RNAs (ncRNAs) (Le Blévec et al, 2020;Zafar et al, 2021). DNA methylation and histone PTMs regulate chromatin accessibility and packaging to control the binding of transcription factors to either facilitate or repress gene expression.…”

Section: The Role Of Dna Methylation During Oocyte Development and Ea...mentioning

confidence: 99%

“…DNA methylation and histone PTMs regulate chromatin accessibility and packaging to control the binding of transcription factors to either facilitate or repress gene expression. On the other hand, ncRNAs are strong post-transcriptional regulators, targeting the 3′ untranslated regions (3′-UTRs) of specified mRNA molecules to induce their degradation (Le Blévec et al, 2020;Zafar et al, 2021).…”

Section: The Role Of Dna Methylation During Oocyte Development and Ea...mentioning

confidence: 99%

Fertilization, Oocyte Activation, Calcium Release and Epigenetic Remodelling: Lessons From Cancer Models

Shafqat

Kashir

Alsalameh

et al. 2022

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

Oocyte activation deficiency (OAD) is the basis of Total Fertilisation Failure (TFF) and is attributed to mutations in the PLCζ gene—termed male factor infertility. This derives abnormal Ca2+ oscillations and could be the main cause of primary disruptions in the gene expression of Ca2+-related proteins. Epigenetic mechanisms are universally accepted as key regulators of gene expression. However, epigenetic dysregulations have not been considered as potential mechanisms of oocyte-borne OAD. Herein, we discuss changes in the DNA methylome during oogenesis and embryogenesis. We further highlight key pathways comprising the oocyte Ca2+ toolkit, which could be targets of epigenetic alterations, especially aberrations in DNA methylation. Considering that the vast majority of epigenetic modifications examined during fertilization revolve around alterations in DNA methylation, we aim in this article to associate Ca2+-specific mechanisms with these alterations. To strengthen this perspective, we bring evidence from cancer research on the intricate link between DNA methylation and Ca2+ signaling as cancer research has examined such questions in a lot more detail. From a therapeutic standpoint, if our hypothesis is proven to be correct, this will explain the cause of TFF in idiopathic cases and will open doors for novel therapeutic targets.

show abstract

Paternal epigenetics: Mammalian sperm provide much more than DNA at fertilization

Cited by 53 publications

References 189 publications

Dynamics of cattle sperm sncRNAs during maturation, from testis to ejaculated sperm

Dynamics of cattle sperm sncRNAs during maturation, from testis to ejaculated sperm

Desmosterol Incorporation Into Ram Sperm Membrane Before Cryopreservation Improves in vitro and in vivo Fertility

Fertilization, Oocyte Activation, Calcium Release and Epigenetic Remodelling: Lessons From Cancer Models

Contact Info

Product

Resources

About