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Male Germline Chromatin

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A special issue of Genes (ISSN 2073-4425). This special issue belongs to the section "Molecular Genetics and Genomics".

Deadline for manuscript submissions: closed (31 December 2018) | Viewed by 41376

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Special Issue Editors

Prof. Dr. Darren Griffin

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Guest Editor

School of Biosciences, University of Kent, Canterbury CT2 7NJ, UK
Interests: chromosomes; cytogenetics; aneuploidy; genome evolution; chromosome segregation; infertility; IVF
Special Issues, Collections and Topics in MDPI journals

Dr. Peter Ellis

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Guest Editor

1. School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK
2. Centre for Interdisciplinary Studies of Reproduction (CISoR),University of Kent, Canterbury, Kent CT2 7NJ, UK
Interests: evolution; reproduction; testis; meiosis; spermatogenesis; DNA damage; chromatin; epigenetics; genomics;

Special Issue Information

Dear Colleagues,

Spermatogenesis requires radical restructuring of germline chromatin at multiple stages, involving co-ordinated waves of DNA methylation and demethylation, histone modification, replacement and removal occurring before, during and after meiosis. This Special Issue will draw together papers addressing all aspects of chromatin organization and dynamics in the male germ line, in humans and in model organisms. In particular, we will invite authors to discuss novel methods for studying germline chromatin structure, the interplay between chromatin structure and susceptibility to DNA damage and mutation, chromatin modifications associated with epigenetic inheritance in the early embryo, and the impact this work has for understanding natural fertility and improving assisted reproduction techniques.

Prof. Darren Griffin
Dr. Peter Ellis
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Genes is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

spermatogenesis
chromatin
nuclear organisation
DNA oxidation
DNA fragmentation
epigenetic inheritance
histone retention
assisted reproduction
in vitro fertilisation

Published Papers (10 papers)

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Editorial

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3 pages, 177 KiB

Open AccessEditorial

Form from Function, Order from Chaos in Male Germline Chromatin

by Peter J. I. Ellis and Darren K. Griffin

Genes 2020, 11(2), 210; https://0-doi-org.brum.beds.ac.uk/10.3390/genes11020210 - 18 Feb 2020

Cited by 1 | Viewed by 1917

Abstract

Spermatogenesis requires radical restructuring of germline chromatin at multiple stages, involving co-ordinated waves of DNA methylation and demethylation, histone modification, replacement and removal occurring before, during and after meiosis. This Special Issue has drawn together papers addressing many aspects of chromatin organization and dynamics in the male germ line, in humans and in model organisms. Two major themes emerge from these studies: the first is the functional significance of nuclear organisation in the developing germline; the second is the interplay between sperm chromatin structure and susceptibility to DNA damage and mutation. The consequences of these aspects for fertility, both in humans and other animals, is a major health and social welfare issue and this is reflected in these nine exciting manuscripts. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

Research

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12 pages, 804 KiB

Open AccessArticle

Telomere Dynamics Throughout Spermatogenesis

by Heather E. Fice and Bernard Robaire

Genes 2019, 10(7), 525; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10070525 - 12 Jul 2019

Cited by 18 | Viewed by 4524

Abstract

Telomeres are repeat regions of DNA that cap either end of each chromosome, thereby providing stability and protection from the degradation of gene-rich regions. Each cell replication causes the loss of telomeric repeats due to incomplete DNA replication, though it is well-established that progressive telomere shortening is evaded in male germ cells by the maintenance of active telomerase. However, germ cell telomeres are still susceptible to disruption or insult by oxidative stress, toxicant exposure, and aging. Our aim was to examine the relative telomere length (rTL) in an outbred Sprague Dawley (SD) and an inbred Brown Norway (BN) rat model for paternal aging. No significant differences were found when comparing pachytene spermatocytes (PS), round spermatids (RS), and sperm obtained from the caput and cauda of the epididymis of young and aged SD rats; this is likely due to the high variance observed among individuals. A significant age-dependent decrease in rTL was observed from 115.6 (±6.5) to 93.3 (±6.3) in caput sperm and from 142.4 (±14.6) to 105.3 (±2.5) in cauda sperm from BN rats. Additionally, an increase in rTL during epididymal maturation was observed in both strains, most strikingly from 115.6 (±6.5) to 142 (±14.6) in young BN rats. These results confirm the decrease in rTL in rodents, but only when an inbred strain is used, and represent the first demonstration that rTL changes as sperm transit through the epididymis. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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17 pages, 2153 KiB

Open AccessArticle

Human Sperm Chromosomes: To Form Hairpin-Loops, Or Not to Form Hairpin-Loops, That Is the Question

by Dimitrios Ioannou and Helen G. Tempest

Genes 2019, 10(7), 504; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10070504 - 03 Jul 2019

Cited by 3 | Viewed by 3116

Abstract

Background: Genomes are non-randomly organized within the interphase nucleus; and spermatozoa are proposed to have a unique hairpin-loop configuration, which has been hypothesized to be critical for the ordered exodus of the paternal genome following fertilization. Recent studies suggest that the hairpin-loop model of sperm chromatin organization is more segmentally organized. The purpose of this study is to examine the 3D organization and hairpin-loop configurations of chromosomes in human spermatozoa. Methods: Three-color sperm-fluorescence in-situ hybridization was utilized against the centromeres, and chromosome p- and q-arms of eight chromosomes from five normozoospermic donors. Wide-field fluorescence microscopy and 3D modelling established the radial organization and hairpin-loop chromosome configurations in spermatozoa. Results: All chromosomes possessed reproducible non-random radial organization (p < 0.05) and formed discrete hairpin-loop configurations. However, chromosomes preferentially formed narrow or wide hairpin-loops. We did not find evidence to support the existence of a centralized chromocenter(s) with centromeres being more peripherally localized than one or both of their respective chromosome arms. Conclusion: This provides further evidence to support a more segmental organization of chromatin in the human sperm nucleus. This may be of significance for fertilization and early embryogenesis as specific genomic regions are likely to be exposed, remodeled, and activated first, following fertilization. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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14 pages, 599 KiB

Open AccessArticle

A Comparison Between Two Assays for Measuring Seminal Oxidative Stress and their Relationship with Sperm DNA Fragmentation and Semen Parameters

by Sheryl T. Homa, Anna M. Vassiliou, Jesse Stone, Aideen P. Killeen, Andrew Dawkins, Jingyi Xie, Farley Gould and Jonathan W. A. Ramsay

Genes 2019, 10(3), 236; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10030236 - 19 Mar 2019

Cited by 70 | Viewed by 5614

Abstract

Oxidative stress (OS) is a significant cause of DNA fragmentation and is associated with poor embryo development and recurrent miscarriage. The aim of this study was to compare two different methods for assessing seminal OS and their ability to predict sperm DNA fragmentation and abnormal semen parameters. Semen samples were collected from 520 men attending for routine diagnostic testing following informed consent. Oxidative stress was assessed using either a chemiluminescence assay to measure reactive oxygen species (ROS) or an electrochemical assay to measure oxidation reduction potential (sORP). Sperm DNA fragmentation (DFI) and sperm with immature chromatin (HDS) were assessed using sperm chromatin structure assay (SCSA). Semen analysis was performed according to WHO 2010 guidelines. Reactive oxygen species sORP and DFI are negatively correlated with sperm motility (p = 0.0012, 0.0002, <0.0001 respectively) and vitality (p < 0.0001, 0.019, <0.0001 respectively). The correlation was stronger for sORP than ROS. Reactive oxygen species (p < 0.0001), sORP (p < 0.0001), DFI (p < 0.0089) and HDS (p < 0.0001) were significantly elevated in samples with abnormal semen parameters, compared to those with normal parameters. Samples with polymorphonuclear leukocytes (PMN) have excessive ROS levels compared to those without (p < 0.0001), but sORP and DFI in this group are not significantly increased. DNA fragmentation was significantly elevated in samples with OS measured by ROS (p = 0.0052) or sORP (p = 0.004). The results demonstrate the multi-dimensional nature of oxidative stress and that neither assay can be used alone in the diagnosis of OS, especially in cases of leukocytospermia. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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18 pages, 5547 KiB

Open AccessArticle

Rescue of Sly Expression Is Not Sufficient to Rescue Spermiogenic Phenotype of Mice with Deletions of Y Chromosome Long Arm

by Jonathan M. Riel, Yasuhiro Yamauchi, Victor A. Ruthig, Qushay U. Malinta, Mélina Blanco, Charlotte Moretti, Julie Cocquet and Monika A. Ward

Genes 2019, 10(2), 133; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10020133 - 12 Feb 2019

Cited by 6 | Viewed by 3074

Abstract

Mice with deletions of the Y-specific (non-PAR) region of the mouse Y chromosome long arm (NPYq) have sperm defects and fertility problems that increase proportionally to deletion size. Mice with abrogated function of NPYq-encoded gene Sly (sh367 Sly-KD) display a phenotype similar to that of NPYq deletion mutants but less severe. The milder phenotype can be due to insufficient Sly knockdown, involvement of another NPYq gene, or both. To address this question and to further elucidate the role of Sly in the infertile phenotype of mice with NPYq deletions, we developed an anti-SLY antibody specifically recognizing SLY1 and SLY2 protein isoforms and used it to characterize SLY expression in NPYq- and Sly-deficient mice. We also carried out transgene rescue by adding Sly1/2 transgenes to mice with NPYq deletions. We demonstrated that SLY1/2 expression in mutant mice decreased proportionally to deletion size, with ~12% of SLY1/2 retained in shSLY sh367 testes. The addition of Sly1/2 transgenes to mice with NPYq deletions rescued SLY1/2 expression but did not ameliorate fertility and testicular/spermiogenic defects. Together, the data suggest that Sly deficiency is not the sole underlying cause of the infertile phenotype of mice with NPYq deletions and imply the involvement of another NPYq gene. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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12 pages, 2289 KiB

Open AccessArticle

Nucleolar Expression and Chromosomal Associations in Robertsonian Spermatocytes of Mus musculus domesticus

by Fernanda López-Moncada, Daniel Tapia, Nolberto Zuñiga, Eliana Ayarza, Julio López-Fenner, Carlo Alberto Redi and Soledad Berríos

Genes 2019, 10(2), 120; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10020120 - 06 Feb 2019

Cited by 2 | Viewed by 2983

Abstract

We studied and compared the nucleolar expression or nucleoli from specific bivalents in spermatocytes of the standard Mus musculus domesticus 2n = 40, of Robertsonian (Rb) homozygotes 2n = 24 and heterozygotes 2n = 32. We analyzed 200 nuclear microspreads of each specific nucleolar chromosome and spermatocyte karyotype, using FISH to identify specific nucleolar bivalents, immunofluorescence for both fibrillarin of the nucleolus and the synaptonemal complex of the bivalents, and DAPI for heterochromatin. There was nucleolar expression in all the chromosomal conditions studied. By specific nucleolar bivalent, the quantitative relative nucleolar expression was higher in the bivalent 12 than in its derivatives, lower in the bivalent 15 than in its derivatives and higher in the bivalent 16 than its Rb derivatives. In the interactions between non-homologous chromosomal domains, the nucleolar bivalents were preferentially associated through pericentromeric heterochromatin with other bivalents of similar morphology and sometimes with other nucleolar bivalents. We suggest that the nucleolar expression in Rb nucleolar chromosomes is modified as a consequence of different localization of ribosomal genes (NOR) in the Rb chromosomes, its proximity to heterochromatin and its associations with chromosomes of the same morphology. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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14 pages, 7347 KiB

Open AccessArticle

Automated Nuclear Cartography Reveals Conserved Sperm Chromosome Territory Localization across 2 Million Years of Mouse Evolution

by Benjamin Matthew Skinner, Joanne Bacon, Claudia Cattoni Rathje, Erica Lee Larson, Emily Emiko Konishi Kopania, Jeffrey Martin Good, Nabeel Ahmed Affara and Peter James Ivor Ellis

Genes 2019, 10(2), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10020109 - 01 Feb 2019

Cited by 6 | Viewed by 3147

Abstract

Measurements of nuclear organization in asymmetric nuclei in 2D images have traditionally been manual. This is exemplified by attempts to measure chromosome position in sperm samples, typically by dividing the nucleus into zones, and manually scoring which zone a fluorescence in-situ hybridisation (FISH) signal lies in. This is time consuming, limiting the number of nuclei that can be analyzed, and prone to subjectivity. We have developed a new approach for automated mapping of FISH signals in asymmetric nuclei, integrated into an existing image analysis tool for nuclear morphology. Automatic landmark detection defines equivalent structural regions in each nucleus, then dynamic warping of the FISH images to a common shape allows us to generate a composite of the signal within the entire cell population. Using this approach, we mapped the positions of the sex chromosomes and two autosomes in three mouse lineages (Mus musculus domesticus, Mus musculus musculus and Mus spretus). We found that in all three, chromosomes 11 and 19 tend to interact with each other, but are shielded from interactions with the sex chromosomes. This organization is conserved across 2 million years of mouse evolution. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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17 pages, 3833 KiB

Open AccessArticle

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

by Alexandre Champroux, Christelle Damon-Soubeyrand, Chantal Goubely, Stephanie Bravard, Joelle Henry-Berger, Rachel Guiton, Fabrice Saez, Joel Drevet and Ayhan Kocer

Genes 2018, 9(10), 501; https://doi.org/10.3390/genes9100501 - 17 Oct 2018

Cited by 17 | Viewed by 4701

Abstract

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. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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Review

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13 pages, 2403 KiB

Open AccessReview

Single and Double Strand Sperm DNA Damage: Different Reproductive Effects on Male Fertility

by Jordi Ribas-Maynou and Jordi Benet

Genes 2019, 10(2), 105; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10020105 - 31 Jan 2019

Cited by 80 | Viewed by 7919

Abstract

Reproductive diseases have become a growing worldwide problem and male factor plays an important role in the reproductive diagnosis, prognosis and design of assisted reproductive treatments. Sperm cell holds the mission of carrying the paternal genetic complement to the oocyte in order to contribute to an euploid zygote with proper DNA integrity. Sperm DNA fragmentation had been used for decades as a male fertility test, however, its usefulness have arisen multiple debates, especially around Intracytoplasmic Sperm Injection (ICSI) treatments. In the recent years, it has been described that different types of sperm DNA breaks (single and double strand DNA breaks) cause different clinical reproductive effects. On one hand, single-strand DNA breaks are present extensively as a multiple break points in all regions of the genome, are related to oxidative stress and cause a lack of clinical pregnancy or an increase of the conception time. On the other hand, double-strand DNA breaks are mainly localized and attached to the sperm nuclear matrix as a very few break points, are possibly related to a lack of DNA repair in meiosis and cause a higher risk of miscarriage, low embryo quality and higher risk of implantation failure in ICSI cycles. The present work also reviews different studies that may contribute in the understanding of sperm chromatin as well as treatments to prevent sperm DNA damage. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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10 pages, 276 KiB

Open AccessReview

Genetic Instability and Chromatin Remodeling in Spermatids

by Tiphanie Cavé, Rebecka Desmarais, Chloé Lacombe-Burgoyne and Guylain Boissonneault

Genes 2019, 10(1), 40; https://0-doi-org.brum.beds.ac.uk/10.3390/genes10010040 - 14 Jan 2019

Cited by 13 | Viewed by 3352

Abstract

The near complete replacement of somatic chromatin in spermatids is, perhaps, the most striking nuclear event known to the eukaryotic domain. The process is far from being fully understood, but research has nevertheless unraveled its complexity as an expression of histone variants and post-translational modifications that must be finely orchestrated to promote the DNA topological change and compaction provided by the deposition of protamines. That this major transition may not be genetically inert came from early observations that transient DNA strand breaks were detected in situ at chromatin remodeling steps. The potential for genetic instability was later emphasized by our demonstration that a significant number of DNA double-strand breaks (DSBs) are formed and then repaired in the haploid context of spermatids. The detection of DNA breaks by 3′OH end labeling in the whole population of spermatids suggests that a reversible enzymatic process is involved, which differs from canonical apoptosis. We have set the stage for a better characterization of the genetic impact of this transition by showing that post-meiotic DNA fragmentation is conserved from human to yeast, and by providing tools for the initial mapping of the genome-wide DSB distribution in the mouse model. Hence, the molecular mechanism of post-meiotic DSB formation and repair in spermatids may prove to be a significant component of the well-known male mutation bias. Based on our recent observations and a survey of the literature, we propose that the chromatin remodeling in spermatids offers a proper context for the induction of de novo polymorphism and structural variations that can be transmitted to the next generation. Full article

(This article belongs to the Special Issue Male Germline Chromatin)

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