Genetic Factors Affecting Sperm Chromatin Structure

Blanco, M. Andrés; Cocquet, Julie

doi:10.1007/978-3-030-21664-1_1

Cited by 9 publications

(14 citation statements)

References 176 publications

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“…Optimal nuclear sperm condensation is one of the major issues in the male germ cell differentiation program and, to achieve this, mammalian sperm go through a complex process during spermiogenesis and post-testicular maturation (for recent reviews, see: [ 1 – 3 ]). The main objective of extreme cyto-differentiation of sperm is to confer special hydrodynamic properties to the smallest and mobile mammalian cell.…”

Section: Introductionmentioning

confidence: 99%

Could high DNA stainability (HDS) be a valuable indicator of sperm nuclear integrity?

Mohammadi

Tavalaee

Gharagozloo

et al. 2020

Basic Clin. Androl.

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Background: The Sperm Chromatin Structure Assay (SCSA®), in addition to identifying the DNA Fragmentation Index (DFI) also identifies High DNA satiability (HDS), supposed to reflect the nuclear compaction of spermatozoa. However, data on what exactly this parameter reveals, its relevance and usefulness are contradictory. In order to shed light on this situation, spermatozoa of a cohort (N = 397) of infertile men were subjected to the SCSA®, TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling) and CMA3 (Chromomycin A3) tests. In a smaller subcohort (N = 100), aniline blue (AB) and toluidine blue (TB) staining were performed in addition. The objective of this study was thus to answer the question of whether HDS is a relevant and reliable parameter to be taken into account? Results: HDS does not appear to be a reliable indicator of nuclear immaturity because it shows a weak correlation with the CMA3, AB and TB stains. The low correlation of HDS with sperm DNA fragmentation (TUNEL and SCSA®) and DNA condensation (CMA3, AB and TB) tests suggests that these two parameters could be decoupled. Unlike DFI and TUNEL, HDS has not been shown to correlate with classic clinical situations of male infertility (asthenozoospermia, teratozoospermia or astheno-teratozoospermia). Conclusion: HDS correlates poorly with most tests that focus specifically on the level of maturity of the sperm nucleus. To our knowledge, this study is the first to compare SCSA®, TUNEL, AB, TB and CMA3 assays on identical samples. It shows the potency, consistency and limitations of each test and the care that must be taken in their interpretation.

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Section: Introductionmentioning

confidence: 99%

Could high DNA stainability (HDS) be a valuable indicator of sperm nuclear integrity?

Mohammadi

Tavalaee

Gharagozloo

et al. 2020

Basic Clin. Androl.

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“…Interestingly, EP300 mediating histone hyperacetylation during spermiogenesis could facilitate histone replacement and chromatin condensation. 50,51 Our study found that EP300 activity was obviously decreased in the THZ1 group (Figure 7b), indicating that CDK7 could also regulate the chromatin concentration of spermatids by directly targeting EP300.…”

Section: Discussionmentioning

confidence: 76%

“…Our results demonstrated that p‐STAT3 and p‐Cortactin levels were significantly decreased after the inhibition of CDK7, suggesting that CDK7 regulated spermatid differentiation by activating the STAT3 molecular pathway (Figure 7b). Interestingly, EP300 mediating histone hyperacetylation during spermiogenesis could facilitate histone replacement and chromatin condensation 50,51 . Our study found that EP300 activity was obviously decreased in the THZ1 group (Figure 7b), indicating that CDK7 could also regulate the chromatin concentration of spermatids by directly targeting EP300.…”

Section: Discussionmentioning

confidence: 77%

“…Studies have demonstrated that STAT3 activity is involved in germ cell apoptosis and sperm motility, 46,47 and CDK7 and EP300 phosphorylates STAT3 to activate it 48,49 . In addition, phosphorylated EP300 regulates chromatin concentration 50,51 . As a result, the levels of p‐EP300 (Ser1834) and p‐STAT3 (Tyr705) in the testes of 3‐week‐old mice were obviously decreased after 400 nM THZ1 treatment for 48 hr (Figure 8b,c).…”

Section: Resultsmentioning

confidence: 91%

“…48,49 In addition, phosphorylated EP300 regulates chromatin concentration. 50,51 As a result, the levels of p-EP300 (Ser1834) and p-STAT3 (Tyr705) in the testes of 3-week-old mice were obviously decreased after 400 nM THZ1 treatment for 48 hr (Figure 8b,c). In the STAT3 signaling pathway, p-STAT3 can regulate the expression of Cortactin.…”

Section: Cdk7 Participates In Spermatid Differentiation By Activating the Stat3 Molecular Pathwaymentioning

confidence: 94%

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Cyclin‐dependent kinase 7 is essential for spermatogenesis by regulating retinoic acid signaling pathways and the STAT3 molecular pathway

Chen

Dai

et al. 2021

IUBMB Life

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Spermatogenesis is a complex process that requires precise regulation. Phosphorylation plays a role in spermatogenesis by regulating protein structure and activity. This study focused on cyclin‐dependent kinase 7 (CDK7), and explored its function and molecular mechanisms in spermatogenesis in vitro in a cell line and in vivo in a mouse model. Inhibition of CDK7 activity affected spermatogonia proliferation and differentiation, and we found that CDK7 regulates retinoic acid (RA)‐mediated c‐KIT expression to play a role in spermatogonia. Then, we demonstrated that inhibition of CDK7 affected meiosis initiation, DNA repair, and synaptonemal complex formation in meiosis progression, and CDK7 played this role by regulating RA‐mediated STRA8 and REC8 signaling pathways. Moreover, inhibition of CDK7 impacted spermatid differentiation and resulted in decreased counts, decreased motility, and increased head deformity of sperm. We demonstrated that CDK7 affects germ cell apoptosis and sperm motility by activating STAT3 and that STAT3 further regulates Cortactin expression to influence the nuclear elongation, chromatin condensation, and acrosome formation of sperm. Additionally, EP300 was identified as another potential target phosphorylated by CDK7 that participates in chromatin condensation. Our results demonstrated the important role of CDK7 in all key aspects of spermatogenesis, potentially providing an effective target for clinical diagnosis and pathogenesis.

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Insights into the sperm chromatin and implications for male infertility from a protein perspective

Iglesia

Jodar

Oliva

et al. 2022

WIREs Mechanisms of Disease

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Male germ cells undergo an extreme but fascinating process of chromatin remodeling that begins in the testis during the last phase of spermatogenesis and continues through epididymal sperm maturation. Most of the histones are replaced by small proteins named protamines, whose high basicity leads to a tight genomic compaction. This process is epigenetically regulated at many levels, not only by posttranslational modifications, but also by readers, writers, and erasers, in a context of a highly coordinated postmeiotic gene expression program. Protamines are key proteins for acquiring this highly specialized chromatin conformation, needed for sperm functionality. Interestingly, and contrary to what could be inferred from its very specific DNA‐packaging function across protamine‐containing species, human sperm chromatin contains a wide spectrum of protamine proteoforms, including truncated and posttranslationally modified proteoforms. The generation of protamine knock‐out models revealed not only chromatin compaction defects, but also collateral sperm alterations contributing to infertile phenotypes, evidencing the importance of sperm chromatin protamination toward the generation of a new individual. The unique features of sperm chromatin have motivated its study, applying from conventional to the most ground‐breaking techniques to disentangle its peculiarities and the cellular mechanisms governing its successful conferment, especially relevant from the protein point of view due to the important epigenetic role of sperm nuclear proteins. Gathering and contextualizing the most striking discoveries will provide a global understanding of the importance and complexity of achieving a proper chromatin compaction and exploring its implications on postfertilization events and beyond. This article is categorized under: Reproductive System Diseases > Genetics/Genomics/Epigenetics Reproductive System Diseases > Molecular and Cellular Physiology

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Genetic Factors Affecting Sperm Chromatin Structure

Cited by 9 publications

References 176 publications

Could high DNA stainability (HDS) be a valuable indicator of sperm nuclear integrity?

Could high DNA stainability (HDS) be a valuable indicator of sperm nuclear integrity?

Cyclin‐dependent kinase 7 is essential for spermatogenesis by regulating retinoic acid signaling pathways and the STAT3 molecular pathway

Insights into the sperm chromatin and implications for male infertility from a protein perspective

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