scholarly journals The role of chromosome segregation and nuclear organisation in human subfertility

2019 ◽  
Vol 47 (1) ◽  
pp. 425-432 ◽  
Author(s):  
Katie E. Fowler ◽  
Anjali A. Mandawala ◽  
Darren K. Griffin
Keyword(s):  
Dna Damage ◽  
Chromosome Segregation ◽  
Academic Research ◽  
Sperm Nucleus ◽  
Sperm Dna Damage ◽  
Male Gametes ◽  
Nuclear Organisation ◽  
Spatio Temporal ◽  
The Right

Abstract Spermatogenesis is central to successful sexual reproduction, producing large numbers of haploid motile male gametes. Throughout this process, a series of equational and reductional chromosome segregation precedes radical repackaging of the haploid genome. Faithful chromosome segregation is thus crucial, as is an ordered spatio-temporal ‘dance’ of packing a large amount of chromatin into a very small space. Ergo, when the process goes wrong, this is associated with an improper chromosome number, nuclear position and/or chromatin damage in the sperm head. Generally, screening for overall DNA damage is relatively commonplace in clinics, but aneuploidy assessment is less so and nuclear organisation studies form the basis of academic research. Several studies have focussed on the role of chromosome segregation, nuclear organisation and analysis of sperm morphometry in human subfertility observing significant alterations in some cases, especially of the sex chromosomes. Importantly, sperm DNA damage has been associated with infertility and both extrinsic (e.g. lifestyle) and intrinsic (e.g. reactive oxygen species levels) factors, and while some DNA-strand breaks are repaired, unexpected breaks can cause differential chromatin packaging and further breakage. A ‘healthy’ sperm nucleus (with the right number of chromosomes, nuclear organisation and minimal DNA damage) is thus an essential part of reproduction. The purpose of this review is to summarise state of the art in the fields of sperm aneuploidy assessment, nuclear organisation and DNA damage studies.

miR-424/322 is downregulated in the semen of patients with severe DNA damage and may regulate sperm DNA damage

2016 ◽  
Vol 28 (10) ◽  
pp. 1598 ◽  
Author(s):  
Kai Zhao ◽  
Yaoping Chen ◽  
Ruifeng Yang ◽  
Yang Bai ◽  
Cuiling Li ◽  
...  
Keyword(s):  
Dna Damage ◽  
Human Sperm ◽  
Vital Role ◽  
Dna Integrity ◽  
Dna Double Strand Breaks ◽  
Human Seminal Plasma ◽  
Sperm Dna Damage ◽  
Sperm Dna ◽  
Murine Homologue

Sperm DNA integrity is an essential factor for accurate transmission of genetic information. Human sperm DNA damage is a common cause of male infertility but the exact mechanism remains poorly understood. Considering the vital role of microRNA (miRNA) in multiple pathophysiological processes, we hypothesised that testicular miRNA is involved in sperm DNA damage during spermatogenesis. Infertile patients with high sperm DNA fragment index (DFI; n = 94) were selected from 1090 infertile men and a total of 18 testis-specific seminal miRNAs previously identified from human seminal plasma were chosen and tested. miR-29c and miR-424 were downregulated in men with high DFI. The inhibition of these two miRNAs in mice confirmed the role of miR-424 (murine homologue miR-322) in sperm DNA damage during spermatogenesis; by contrast, miR-29c exhibited a negative result. Thus, miR-424/322 is involved in sperm DNA damage. Furthermore, the dysregulation of this miRNA can induce DNA double-strand breaks during spermatogenesis.

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

Genes ◽  
2018 ◽  
Vol 9 (10) ◽  
pp. 501 ◽  
Author(s):  
Alexandre Champroux ◽  
Christelle Damon-Soubeyrand ◽  
Chantal Goubely ◽  
Stephanie Bravard ◽  
Joelle Henry-Berger ◽  
...  
Keyword(s):  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Sperm Nucleus ◽  
Sperm Chromatin ◽  
Sperm Dna Fragmentation ◽  
Chromosome 2 ◽  
Mouse Sperm ◽  
Sperm Dna Damage ◽  
Chromosome Architecture ◽  
Sperm Dna

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.

scholarly journals A mitosis-specific and R loop–driven ATR pathway promotes faithful chromosome segregation

Science ◽  
2017 ◽  
Vol 359 (6371) ◽  
pp. 108-114 ◽  
Author(s):  
Lilian Kabeche ◽  
Hai Dang Nguyen ◽  
Rémi Buisson ◽  
Lee Zou
Keyword(s):  
Dna Damage ◽  
Chromosome Segregation ◽  
Stress Responses ◽  
Chromosome Instability ◽  
Protein A ◽  
Aurora B ◽  
Cyclin Dependent Kinase ◽  
Ataxia Telangiectasia Mutated ◽  
Atr Kinase

The ataxia telangiectasia mutated and Rad3-related (ATR) kinase is crucial for DNA damage and replication stress responses. Here, we describe an unexpected role of ATR in mitosis. Acute inhibition or degradation of ATR in mitosis induces whole-chromosome missegregation. The effect of ATR ablation is not due to altered cyclin-dependent kinase 1 (CDK1) activity, DNA damage responses, or unscheduled DNA synthesis but to loss of an ATR function at centromeres. In mitosis, ATR localizes to centromeres through Aurora A–regulated association with centromere protein F (CENP-F), allowing ATR to engage replication protein A (RPA)–coated centromeric R loops. As ATR is activated at centromeres, it stimulates Aurora B through Chk1, preventing formation of lagging chromosomes. Thus, a mitosis-specific and R loop–driven ATR pathway acts at centromeres to promote faithful chromosome segregation, revealing functions of R loops and ATR in suppressing chromosome instability.

Role of Oxidative Stress in the Etiology of Sperm DNA Damage

2011 ◽  
pp. 277-293 ◽  
Author(s):  
R. John Aitken ◽  
Geoffry N. De Iuliis
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Sperm Dna Damage ◽  
Sperm Dna

Role of Sperm DNA Damage in Male Infertility Assessment

2019 ◽  
pp. 57-68 ◽  
Author(s):  
Saradha Baskaran ◽  
Chak-Lam Cho ◽  
Ashok Agarwal
Keyword(s):  
Dna Damage ◽  
Male Infertility ◽  
Sperm Dna Damage ◽  
Sperm Dna

scholarly journals DNA damage response clamp loader Rad24(Rad17) and Mec1(ATR) kinase have distinct functions in regulating meiotic crossovers

2019 ◽  
Author(s):  
Miki Shinohara ◽  
Douglas K. Bishop ◽  
Akira Shinohara
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Chromosome Segregation ◽  
Clamp Loader ◽  
Tetrad Analysis ◽  
Ectopic Recombination ◽  
Damage Response ◽  
Specific Manner ◽  
Atr Kinase

AbstractCrossover (CO) recombination is essential for chromosome segregation during meiosis I. The number and distribution of COs are tightly regulated during meiosis. CO control includes CO assurance and CO interference, which guarantee at least one CO per a bivalent and evenly-spaced CO distribution, respectively. Previous studies showed the role of DNA damage response (DDR) clamp and its loader in efficient formation of meiotic COs by promoting the recruitment of a pro-CO protein Zip3 and interhomolog recombination, and also by suppressing ectopic recombination. In this study, by classical tetrad analysis ofSaccharomyces cerevisiae, we showed that a mutant defective in theRAD24 gene(RAD17in other organisms), which encodes the DDR clamp loader, displayed reduced CO frequencies on two shorter chromosomes (IIIandV) but not on a long chromosome (chromosomeVII). The residual COs in therad24mutant do not show interference. In contrast to therad24mutant, mutants defective in the ATR kinase homolog Mec1/Esr1, including amec1null and amec1kinase-dead mutant, show little or no defect in CO frequency. On the other hand,mec1COs show defects in interference, similar to therad24mutant. Moreover, CO formation and its control are implemented in a chromosome-specific manner, which may reflect a role for chromosome size in regulation.

scholarly journals Why Should We Care What Extremists Think? The Contribution of Emic Perspectives to Understanding the “right-wing extremist” Mind-Set

2021 ◽  
pp. 089124162110411
Author(s):  
Hilary Pilkington
Keyword(s):  
Academic Research ◽  
Ethnographic Research ◽  
Right Wing ◽  
Policy And Practice ◽  
Far Right ◽  
Mind Set ◽  
The Right ◽  
The Mind ◽  
Right Wing Extremism

This article considers the implications of the mainstreaming of ‘right-wing extremism’ for what, and whom, we understand as ‘extreme’. It draws on ethnographic research (2017-2020) with young people active in movements routinely referred to in public and academic discourse as ‘extreme right’ or ‘far right’. Based on interviews, informal communication and observation, the article explores how actors in the milieu understand ‘extremism’ and how far this corresponds to academic and public conceptualisations of ‘right-wing extremism’, in particular cognitive ‘closed-mindedness’. Emic perspectives are not accorded privileged authenticity. Rather, it is argued, critical engagement with them reveals the important role of ethnographic research in gaining insight into, and challenging what we know about, the ‘mind-set’ of right-wing extremists. Understanding if such a mind-set exists, and if it does, in what it consists, matters, if academic research is to inform policy and practice to counter socially harmful practices among those it targets effectively.

Sign in / Sign up

Export Citation Format

Share Document