Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

Chioccarelli, Teresa; Pierantoni, Riccardo; Manfrevola, Francesco; Porreca, Veronica; Fasano, Silvia; Chianese, Rosanna; Cobellis, Gilda

doi:10.3390/jcm9030640

Cited by 44 publications

(105 citation statements)

References 303 publications

(397 reference statements)

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“…Beyond haploid nuclear genome, SPZ are important vectors of the epigenetic signature for the zygote, deemed crucial for normal embryo development ( 8 , 36 ). The sperm nucleus needs to reduce the size by packing its genome, through the replacement of histones with protamines ( 37 , 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Mature sperm cells contain several types of RNAs with a potential key role in the oocyte upon fertilization (7,8). Using a microarray strategy, the mRNA fingerprint has been drawn in fertile men (9) as well as in asthenozoospermic patients (10).…”

Section: Introductionmentioning

confidence: 99%

“…Until today, the characterization of a circular RNA (circRNA) cargo in SPZ, collected from infertile men, has never been carried out. The role of circRNA has been deeply investigated in both pathological and physiological conditions (8,16). With regard to reproductive organs, circRNAs has been identified in both testis and ovary (17,18) and their distribution has been correlated to germ cell progression (19).…”

Section: Introductionmentioning

confidence: 99%

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CircRNA Role and circRNA-Dependent Network (ceRNET) in Asthenozoospermia

et al. 2020

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The role of circRNA in reproduction is under investigation. CircRNAs are expressed in human testis, spermatozoa (SPZ), and seminal plasma. Their involvement in embryo development has also been suggested. Asthenozoospermia, a common cause of male infertility, is characterized by reduced or absent sperm motility in fresh ejaculate. While abnormal mitochondrial function, altered sperm tail, and genomic causes have been deeply investigated, the epigenetic signature of asthenozoospermic derived SPZ still remains unexplored. CircRNAs may take part in the repertoire of differentially expressed molecules in infertile men. Considering this background, we carried out a circRNA microarray, identifying a total of 9,138 transcripts, 22% of them novel based and 83.5% with an exonic structure. Using KEGG analysis, we evaluated the circRNA contribution in pathways related to mitochondrial function and sperm motility. In order to discriminate circRNAs with a differential expression in SPZ with differential morphological parameters, we separated sperm cells by Percoll gradient and analyzed their differential circRNA payload. A bioinformatic approach was then utilized to build a circRNA/miRNA/mRNA network. With the aim to demonstrate a dynamic contribution of circRNAs to the sperm epigenetic signature, we verified their modulation as a consequence of an oral amino acid supplementation, efficacious in improving SPZ motility.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CircRNA Role and circRNA-Dependent Network (ceRNET) in Asthenozoospermia

et al. 2020

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“…In particular, using WT and CB1 -/mice, we analyzed the gene expression of Cdyl and Brdt, as a significant player in histone removal, and analyzed the histone H4tetraAc levels, as a main signal of histone displacement [8]. Histone H3 was used for monitoring efficiency of histone displacement and normalized histone H4tetraAc levels.…”

Section: Characterization Of Intra-testicular E 2 Deficit and Histonementioning

confidence: 99%

“…The combined histone H4 acetylation at lysine (K) residues K5, K8, K12, and K16 results in the main signal of global histone removal as the Bromodomain testis-specific protein (BRDT) reads and binds acetyl lysine eliciting histone displacement [7]. Additional histone PTMs are involved in this process [8]. The histone crotonylation is a new histone PTMs recently characterized in mouse germ cells [9,10].…”

Section: Introductionmentioning

confidence: 99%

The Cannabinoid Receptor CB1 Stabilizes Sperm Chromatin Condensation Status During Epididymal Transit by Promoting Disulphide Bond Formation

Chioccarelli

Manfrevola

Porreca

et al. 2020

IJMS

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The cannabinoid receptor CB1 regulates differentiation of spermatids. We recently characterized spermatozoa from caput epididymis of CB1-knock-out mice and identified a considerable number of sperm cells with chromatin abnormality such as elevated histone content and poorly condensed chromatin. In this paper, we extended our findings and studied the role of CB1 in the epididymal phase of chromatin condensation of spermatozoa by analysis of spermatozoa from caput and cauda epididymis of wild-type and CB1-knock-out mouse in both a homozygous or heterozygous condition. Furthermore, we studied the impact of CB1-gene deletion on histone displacement mechanism by taking into account the hyperacetylation of histone H4 and players of displacement such as Chromodomain Y Like protein (CDYL) and Bromodomain testis-specific protein (BRDT). Our results show that CB1, via local and/or endocrine cell-to-cell signaling, modulates chromatin remodeling mechanisms that orchestrate a nuclear condensation extent of mature spermatozoa. We show that CB1-gene deletion affects the epididymal phase of chromatin condensation by interfering with inter-/intra-protamine disulphide bridges formation, and deranges the efficiency of histone removal by reducing the hyper-acetylation of histone H4. This effect is independent by gene expression of Cdyl and Brdt mRNA. Our results reveal a novel and important role for CB1 in sperm chromatin condensation mechanisms.

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Circular RNAs: Novel potential regulators in embryogenesis, female infertility, and pregnancy‐related diseases

Gao

Wang

Pan

et al. 2021

Journal Cellular Physiology

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Circular RNAs (circRNAs) are endogenous noncoding RNAs with unique cyclic structures. Although they were previously considered as nonfunctional transcription byproducts, numerous studies have demonstrated that circRNAs regulate gene transcription and expression via different mechanisms. Reproductive health influences the quality of life and affects offspring propagation in women. CircRNAs have been found to modify pregnancy‐related diseases, gynecologic cancers, polycystic ovary syndrome, aging, gamete, and embryo development. It's promising for circRNAs to be the novel diagnostic and therapeutic targets for multiple reproductive diseases. With the widespread application of assisted reproduction technology (ART), it has been revealed that circRNA identification contributes to estimating the quality of gametes and embryos, reflecting the success rate of ART. CRISPR‐Cas9 gene editing technology has enabled the discovery of new roles of circRNAs. So far, the roles of circRNAs in the reproductive system remain poorly defined. In this review, we describe the classification and functions of circRNAs in embryogenesis and the female reproductive system diseases, revealing potential roles of circRNAs physiologically and pathologically. In so‐doing, we provide ideas for developing circRNA‐based therapeutic treatment and clinical application of various female reproductive system diseases.

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Histone Post-Translational Modifications and CircRNAs in Mouse and Human Spermatozoa: Potential Epigenetic Marks to Assess Human Sperm Quality

Cited by 44 publications

References 303 publications

CircRNA Role and circRNA-Dependent Network (ceRNET) in Asthenozoospermia

CircRNA Role and circRNA-Dependent Network (ceRNET) in Asthenozoospermia

The Cannabinoid Receptor CB1 Stabilizes Sperm Chromatin Condensation Status During Epididymal Transit by Promoting Disulphide Bond Formation

Circular RNAs: Novel potential regulators in embryogenesis, female infertility, and pregnancy‐related diseases

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