Chromatin status in human ejaculated spermatozoa from infertile patients and relationship to seminal parameters

Molina, Juan Antonio Maldonado; Castilla, José Antonio; Castaño, J.L.; Fontes, Juan Torres; Mendoza, Noelia; Martínez, Laura García

doi:10.1093/humrep/16.3.534

Cited by 17 publications

(11 citation statements)

References 45 publications

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“…In five studies, the level of sperm DNA damage in infertile men with varicocele was similar to that of infertile men without varicocele (61,(63)(64)(65)(66). In the other four studies, the level of sperm DNA damage in infertile men with varicocele was higher than that of infertile men without varicocele, although it is important to note that the varicocele group generally had poorer semen parameters than the men without varicocele (58)(59)(60)62).…”

Section: Discussion: Are Varicoceles Associated With Increased Dna Frmentioning

confidence: 82%

“…Nine of these case-control studies compared highly selected populations (e.g., infertile men with clinical varicocele) with fertile donors (and/or infertile men without varicocele), making it difficult to attribute the sperm DNA damage to the varicocele rather than the infertility per se (58)(59)(60)(61)(62)(63)(64)(65)(66). In five studies, the level of sperm DNA damage in infertile men with varicocele was similar to that of infertile men without varicocele (61,(63)(64)(65)(66).…”

Section: Discussion: Are Varicoceles Associated With Increased Dna Frmentioning

confidence: 99%

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Are varicoceles associated with increased deoxyribonucleic acid fragmentation?

Zini

Dohle

2011

Fertility and Sterility

153

101

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Section: Discussion: Are Varicoceles Associated With Increased Dna Frmentioning

confidence: 82%

Section: Discussion: Are Varicoceles Associated With Increased Dna Frmentioning

confidence: 99%

Are varicoceles associated with increased deoxyribonucleic acid fragmentation?

Zini

Dohle

2011

Fertility and Sterility

153

101

View full text Add to dashboard Cite

“…Impairment of sperm chromatin condensation is common in infertile male patients (13,22). However, the molecular mechanisms underlying these defects remain largely obscure.…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of SSTK, a Serine/Threonine Protein Kinase Essential for Male Fertility

Spiridonov

Wong

Zerfas

et al. 2005

Molecular and Cellular Biology

122

129

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Here we describe and characterize a small serine/threonine kinase (SSTK) which consists solely of the Nand C-lobes of a protein kinase catalytic domain. SSTK protein is highly conserved among mammals, and no close homologues were found in the genomes of nonmammalian organisms. SSTK specifically interacts with HSP90-1␤, HSC70, and HSP70 proteins, and this association appears to be required for SSTK kinase activity. The SSTK transcript was most abundant in human and mouse testes but was also detected in all human tissues tested. In the mouse testis, SSTK protein was localized to the heads of elongating spermatids. Targeted deletion of the SSTK gene in mice resulted in male sterility due to profound impairment in motility and morphology of spermatozoa. A defect in DNA condensation in SSTK null mutants occurred in elongating spermatids at a step in spermiogenesis coincident with chromatin displacement of histones by transition proteins. SSTK phosphorylated histones H1, H2A, H2AX, and H3 but not H2B or H4 or transition protein 1 in vitro. These results demonstrate that SSTK is required for proper postmeiotic chromatin remodeling and male fertility. Abnormal sperm chromatin condensation is common in sterile men, and our results may provide insight into the molecular mechanisms underlying certain human infertility disorders.Phosphorylation of serine, threonine, and tyrosine residues in substrate targets by protein kinases is a common posttranslational protein modification in eukaryotes and provides a fundamental mechanism for the control of cellular events. Cell division and growth, adhesion and migration, metabolic activity and responses upon environmental stimuli, cell to cell communication, signal transduction, and apoptosis are among the many processes regulated by protein kinases (15,16). At the molecular level, phosphorylation and dephosphorylation of enzymes allow fast and sensitive regulation of enzyme activity and are also a major mechanism of transmembrane signaling and signal amplification in the branching network of intracellular protein kinase cascades that ultimately control gene expression by phosphorylation of transcription factors. Phosphorylation of protein substrates can provide binding sites for protein domains which recognize specific phosphorylated amino acid sequences, thereby mediating protein-protein interactions. Protein kinases constitute a large superfamily of related enzymes which contain 12 conserved subdomains folded into N-and C-lobes of the catalytic domain. The superfamily is subdivided into protein serine/threonine kinases, protein tyrosine kinases, and atypical kinases on the basis of substrate specificity (14,16).Phosphorylation events play a central role in chromatin remodeling during mitosis in somatic cells and during meiosis in mammalian spermiogenesis (2, 10). Much less is known about the mechanisms of postmeiotic chromatin condensation. The structure of chromatin changes dramatically during postmeiotic spermiogenesis, as germ cells develop from round spermatids to fully differ...

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“…The charge action of SMA probably inhibits the negative charge neutralization leading to unpacking of the DNA, chromatin decondensation and swelling of the sperm head. Chromatin decondensation is known to be associated with subfertility and infertility [10]. The contraceptive action of RISUG administration is, in part, accounted for by this factor.…”

Section: Discussionmentioning

confidence: 99%