MicroRNA signature in spermatozoa and seminal plasma of proven fertile men and in testicular tissue of men with obstructive azoospermia

Abu‐Halima, Masood; Galata, Valentina; Backes, Christina; Keller, Andreas; Hammadeh, Mohamad Eid; Meese, Eckart

doi:10.1111/and.13503

Cited by 19 publications

(10 citation statements)

References 43 publications

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“…USPs are well-known deubiquitinating enzymes with key roles in spermatogenesis: USP9 deletion has been discovered in infertile men ( 54 ), polymorphisms in USP26 have been associated with infertility ( 55 ), male mice lacking USP2 have severe defects in sperm motility ( 56 ), and USP30 regulates mitochondrial morphology ( 26 ). Both SPZ and seminal plasma have a specific miRNA signature that differentially changes in infertile men ( 57 ). CircUSP54— through has-miR-4482-3p—controls the expression of both SOD2 and IBA57P , an enzyme that converts superoxide to less reactive hydrogen peroxide ( 58 ) and a protein located in the mitochondrial matrix, essential for mitochondrial DNA maintenance ( 59 ), respectively.…”

Section: Discussionmentioning

confidence: 99%

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%

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

et al. 2020

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“…Similarly to animal models, several studies suggest that in humans the dysregulated expression of miR-34/449 family members is strongly associated with failed spermatogenesis, with impaired testicular functionality and subsequently with male infertility ( 79 – 82 ). Considering the expression motifs of the miR-34/449 family members in the male reproductive system, data indicate that these microRNAs are expressed in both spermatozoa and testicular tissues but not in the accessory glands, highlighting the possible implication of miR-34/449 family in male infertility originating from testicular dysfunction ( 83 ).…”

Section: Male Infertility In Humans and Mir-34/449 Associationsmentioning

confidence: 99%

Investigating the Role of the microRNA-34/449 Family in Male Infertility: A Critical Analysis and Review of the Literature

Pantos¹,

Grigoriadis

Tomara

et al. 2021

Front. Endocrinol.

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There is a great body of evidence suggesting that in both humans and animal models the microRNA-34/449 (miR-34/449) family plays a crucial role for normal testicular functionality as well as for successful spermatogenesis, regulating spermatozoa maturation and functionality. This review and critical analysis aims to summarize the potential mechanisms via which miR-34/449 dysregulation could lead to male infertility. Existing data indicate that miR-34/449 family members regulate ciliogenesis in the efferent ductules epithelium. Upon miR-34/449 dysregulation, ciliogenesis in the efferent ductules is significantly impaired, leading to sperm aggregation and agglutination as well as to defective reabsorption of the seminiferous tubular fluids. These events in turn cause obstruction of the efferent ductules and thus accumulation of the tubular fluids resulting to high hydrostatic pressure into the testis. High hydrostatic pressure progressively leads to testicular dysfunction as well as to spermatogenic failure and finally to male infertility, which could range from severe oligoasthenozoospermia to azoospermia. In addition, miR-34/449 family members act as significant regulators of spermatogenesis with an essential role in controlling expression patterns of several spermatogenesis-related proteins. It is demonstrated that these microRNAs are meiotic specific microRNAs as their expression is relatively higher at the initiation of meiotic divisions during spermatogenesis. Moreover, data indicate that these molecules are essential for proper formation as well as for proper function of spermatozoa per se. MicroRNA-34/449 family seems to exert significant anti-oxidant and anti-apoptotic properties and thus contribute to testicular homeostatic regulation. Considering the clinical significance of these microRNAs, data indicate that the altered expression of the miR-34/449 family members is strongly associated with several aspects of male infertility. Most importantly, miR-34/449 levels in spermatozoa, in testicular tissues as well as in seminal plasma seem to be directly associated with severity of male infertility, indicating that these microRNAs could serve as potential sensitive biomarkers for an accurate individualized differential diagnosis, as well as for the assessment of the severity of male factor infertility. In conclusion, dysregulation of miR-34/449 family detrimentally affects male reproductive potential, impairing both testicular functionality as well as spermatogenesis. Future studies are needed to verify these conclusions.

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“…These miRNAs are involved in many, if not all, cellular and biological processes investigated, including in the spermatogenesis process and during the early stages of embryonic development 5,8‐10 . Of these miRNAs, miR‐23a and miR‐23b demonstrated a dysregulated abundance level in spermatozoa, seminal plasma‐derived exosomes, and testicular tissue of subfertile men compared to fertile men 11‐15 . Recently, increased amounts of miR‐23a/b‐3p and reduced amounts of testis‐specific transcripts were experimentally validated in the spermatozoa and testicular tissues of oligoasthenozoospermic men as compared to that in normozoospermic men 11 .…”

Section: Introductionmentioning

confidence: 99%