A model for the control of DNA integrity by the sperm nuclear matrix

Gawecka, Joanna E.; Ribas-Maynou, Jordi; Benet, Jordi; Ward, W. Steven

doi:10.4103/1008-682x.153853

Cited by 18 publications

(8 citation statements)

References 65 publications

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“…It should also be remembered that strand breaks occur naturally during DNA supercoiling and relaxation ( 17 – 19 , 23 , 26 ). For this reason, we are presenting the published studies on the basis of the different methods used to assess sperm chromatin integrity in testicular cancer.…”

Section: Sperm Dna Damage In Testicular Cancermentioning

confidence: 99%

“…This is made possible by the binding of DNA with protamines ( 4 – 11 ), which collapse into a toroidal structure and anchor to matrix-associated regions ( 12 – 14 ). Correct DNA-matrix structure is required to replicate male pronuclear DNA and control nuclear integrity after fertilization, since the nuclear matrix plays a pivotal role ( 15 – 17 ). This specific chromatin organization is associated with the recruitment, integrity and function of DNA repair components ( 18 ).…”

Section: Introductionmentioning

confidence: 99%

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Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

et al. 2018

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Testicular cancer (TC) is one of the most treatable of all malignancies and the management of the quality of life of these patients is increasingly important, especially with regard to their sexuality and fertility. Survivors must overcome anxiety and fears about reduced fertility and possible pregnancy-related risks as well as health effects in offspring. There is thus a growing awareness of the need for reproductive counseling of cancer survivors. Studies found a high level of sperm DNA damage in TC patients in comparison with healthy, fertile controls, but no significant difference between these patients and infertile patients. Sperm DNA alterations due to cancer treatment persist from 2 to 5 years after the end of the treatment and may be influenced by both the type of therapy and the stage of the disease. Population studies reported a slightly reduced overall fertility of TC survivors and a more frequent use of ART than the general population, with a success rate of around 50%. Paternity after a diagnosis of cancer is an important issue and reproductive potential is becoming a major quality of life factor. Sperm chromatin instability associated with genome instability is the most important reproductive side effect related to the malignancy or its treatment. Studies investigating the magnitude of this damage could have a considerable translational importance in the management of cancer patients, as they could identify the time needed for the germ cell line to repair nuclear damage and thus produce gametes with a reduced risk for the offspring.

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Section: Sperm Dna Damage In Testicular Cancermentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

et al. 2018

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“…The localization of specific chromosomal regions such as telomeres and centromeres were also investigated in the human sperm nucleus [ 17 , 18 ]. As is the case in somatic cells, sperm cell chromosomes are attached to a nuclear protein scaffold, called the sperm nuclear matrix, which consolidates the structure [ 19 , 20 , 21 ]. Here too, the manner in which chromosomes are attached to the sperm nuclear matrix is unique to that cell lineage and is dissimilar to the somatic situation [ 19 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Nuclear Integrity but Not Topology of Mouse Sperm Chromosome is Affected by Oxidative DNA Damage

Champroux

Damon-Soubeyrand

Goubely

et al. 2018

Genes

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Recent studies have revealed a well-defined higher order of chromosome architecture, named chromosome territories, in the human sperm nuclei. The purpose of this work was, first, to investigate the topology of a selected number of chromosomes in murine sperm; second, to evaluate whether sperm DNA damage has any consequence on chromosome architecture. Using fluorescence in situ hybridization, confocal microscopy, and 3D-reconstruction approaches we demonstrate that chromosome positioning in the mouse sperm nucleus is not random. Some chromosomes tend to occupy preferentially discrete positions, while others, such as chromosome 2 in the mouse sperm nucleus are less defined. Using a mouse transgenic model (Gpx5−/−) of sperm nuclear oxidation, we show that oxidative DNA damage does not disrupt chromosome organization. However, when looking at specific nuclear 3D-parameters, we observed that they were significantly affected in the transgenic sperm, compared to the wild-type. Mild reductive DNA challenge confirmed the fragility of the organization of the oxidized sperm nucleus, which may have unforeseen consequences during post-fertilization events. These data suggest that in addition to the sperm DNA fragmentation, which is already known to modify sperm nucleus organization, the more frequent and, to date, the less highly-regarded phenomenon of sperm DNA oxidation also affects sperm chromatin packaging.

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“…[28][29][30][31] However, despite this safeguarding mechanism, the DNA is still prone to damage in this compacted state. 32,33 Protamine deficiencies show an inverse correlation with DNA fragmentation, 34 and insufficient nucleosome-to-protamine remodeling is associated with infertility. 35 DNA replication is an integral process in all living organisms, yet DNA is highly vulnerable to damage.…”

Section: Natural Sperm Dna Repair Mechanismsmentioning

confidence: 99%

Sperm DNA fragmentation testing in clinical management of reproductive medicine

Adler,

Roth,

Lundy

et al. 2023

Reprod Medicine & Biology

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BackgroundApproximately 8%–12% of couples worldwide face infertility, with infertility of individuals assigned male at birth (AMAB) contributing to at least 50% of cases. Conventional semen analysis commonly used to detect sperm abnormalities is insufficient, as 30% of AMAB patients experiencing infertility show normal results in this test. From a genetic perspective, the assessment of sperm DNA fragmentation (SDF) is important as a parameter of sperm quality.MethodsIn this narrative study, we review and discuss pathophysiological causes, DNA repair mechanisms, and management of high SDF. We then summarize literature exploring the association between SDF and reproductive outcomes.Main FindingsRecent systematic reviews and meta‐analyses have revealed a significant association between high SDF in AMAB individuals and adverse reproductive outcomes including embryo development, natural conception, intrauterine insemination, and in vitro fertilization. However, the association with live birth rates and pregnancy rates following intracytoplasmic injection remains inconclusive. The disparities among quantitative assays, inconsistent reference range values, absent high‐quality prospective clinical trials, and clinical heterogeneity in AMAB patients with elevated SDF represent the main limitations affecting SDF testing.ConclusionThe evaluation and management of SDF plays an important role in a subset of AMAB infertility, but widespread integration into clinical guidelines will require future high‐quality clinical trials and assay standardization.

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A model for the control of DNA integrity by the sperm nuclear matrix

Cited by 18 publications

References 65 publications

Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

Fatherhood and Sperm DNA Damage in Testicular Cancer Patients

Nuclear Integrity but Not Topology of Mouse Sperm Chromosome is Affected by Oxidative DNA Damage

Sperm DNA fragmentation testing in clinical management of reproductive medicine

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