scholarly journals Epigenetic regulation in male germ cells

Reproduction ◽  
2008 ◽  
Vol 136 (2) ◽  
pp. 131-146 ◽  
Author(s):  
Natasha M Zamudio ◽  
Suyinn Chong ◽  
Moira K O'Bryan
Keyword(s):  
Germ Cells ◽  
Epigenetic Regulation ◽  
Sex Chromosome ◽  
Current Knowledge ◽  
Regulation Of Gene Expression ◽  
Male Meiosis ◽  
Paternal Effects ◽  
Male Germ Cells ◽  
Epigenetic Effects ◽  
Meiotic Sex Chromosome Inactivation

In recent years, it has become increasingly clear that epigenetic regulation of gene expression is critical during spermatogenesis. In this review, the epigenetic regulation and the consequences of its aberrant regulation during mitosis, meiosis and spermiogenesis are described. The current knowledge on epigenetic modifications that occur during male meiosis is discussed, with special attention on events that define meiotic sex chromosome inactivation. Finally, the recent studies focused on transgenerational and paternal effects in mice and humans are discussed. In many cases, these epigenetic effects resulted in impaired fertility and potentially long-ranging affects underlining the importance of research in this area.

scholarly journals Healthy ageing and spermatogenesis

Reproduction ◽  
2021 ◽  
Vol 161 (4) ◽  
pp. R89-R101
Author(s):  
Eva Pohl ◽  
Jörg Gromoll ◽  
Joachim Wistuba ◽  
Sandra Laurentino
Keyword(s):  
Stem Cell ◽  
Germ Cells ◽  
Current Knowledge ◽  
Hormone Secretion ◽  
Healthy Ageing ◽  
Hormone Production ◽  
Male Germ Cells ◽  
Cell Niche ◽  
Stem Cell Populations ◽  
The Impact

Delayed family planning and increased parental age increase the risk for infertility and impaired offspring health. While the impact of ageing on oogenesis is well studied, this is less understood on spermatogenesis. Assessing ageing effects on the male germline presents a challenge in differentiating between the effects of ageing-associated morbidities, infertility and ‘pure’ ageing. However, understanding the impact of ageing on male germ cells requires the separation of age from other factors. In this review, we therefore discuss the current knowledge on healthy ageing and spermatogenesis. Male ageing has been previously associated with declining sperm parameters, disrupted hormone secretion and increased time-to-pregnancy, among others. However, recent data show that healthy ageing does not deteriorate testicular function in terms of hormone production and spermatogenic output. In addition, intrinsic, age-dependent, highly specific processes occur in ageing germ cells that are clearly distinct from somatic ageing. Changes in spermatogonial stem cell populations indicate compensation for stem cell exhaustion. Alterations in the stem cell niche and molecular ageing signatures in sperm can be observed in ageing fertile men. DNA fragmentation rates as well as changes in DNA methylation patterns and increased telomere length are hallmarks of ageing sperm. Taken together, we propose a putative link between the re-activation of quiescent Adark spermatogonia and molecular changes in aged sperm descending from these activated spermatogonia. We suggest a baseline of ‘pure' age effects in male germ cells which can be used for subsequent studies in which the impact of infertility or co-morbidities will be studied.

scholarly journals Control of KIT signalling in male germ cells: what can we learn from other systems?

Reproduction ◽  
2009 ◽  
Vol 138 (5) ◽  
pp. 743-757 ◽  
Author(s):  
Sridurga Mithraprabhu ◽  
Kate L Loveland
Keyword(s):  
Germ Cell ◽  
Germ Cells ◽  
Current Knowledge ◽  
Cell Maturation ◽  
Biological Processes ◽  
Limited Information ◽  
Male Germ Cells ◽  
Endogenous Factors ◽  
Kit Ligand ◽  
Spermatogonial Proliferation

The KIT ligand (KITL)/KIT-signalling system is among several pathways known to be essential for fertility. In the postnatal testis, the KIT/KITL interaction is crucial for spermatogonial proliferation, differentiation, survival and subsequent entry into meiosis. Hence, identification of endogenous factors that regulateKITsynthesis is important for understanding the triggers driving germ cell maturation. Although limited information is available regarding local factors in the testicular microenvironment that modulateKITsynthesis at the onset of spermatogenesis, knowledge from other systems could be used as a basis for identifying how KIT function is regulated in germ cells. This review describes the known regulators of KIT, including transcription factors implicated inKITpromoter regulation. In addition, specific downstream outcomes in biological processes that KIT orchestrates are addressed. These are discussed in relationship to current knowledge of mammalian germ cell development.

scholarly journals Meiotic Double-Strand Break Processing and Crossover Patterning Are Regulated in a Sex-Specific Manner by BRCA1–BARD1 in Caenorhabditis elegans

Genetics ◽  
2020 ◽  
Vol 216 (2) ◽  
pp. 359-379 ◽  
Author(s):  
Qianyan Li ◽  
Sara Hariri ◽  
JoAnne Engebrecht
Keyword(s):  
Caenorhabditis Elegans ◽  
Meiotic Recombination ◽  
Sex Chromosome ◽  
Strand Break ◽  
Male Meiosis ◽  
Female Meiosis ◽  
Link Type ◽  
Meiotic Sex Chromosome Inactivation ◽  
Specific Manner ◽  
Dna End Resection

Meiosis is regulated in a sex-specific manner to produce two distinct gametes, sperm and oocytes, for sexual reproduction. To determine how meiotic recombination is regulated in spermatogenesis, we analyzed the meiotic phenotypes of mutants in the tumor suppressor E3 ubiquitin ligase BRC-1-BRD-1 complex in Caenorhabditis elegans male meiosis. Unlike in mammals, this complex is not required for meiotic sex chromosome inactivation, the process whereby hemizygous sex chromosomes are transcriptionally silenced. Interestingly, brc-1 and brd-1 mutants show meiotic recombination phenotypes that are largely opposing to those previously reported for female meiosis. Fewer meiotic recombination intermediates marked by the recombinase RAD-51 were observed in brc-1 and brd-1 mutants, and the reduction in RAD-51 foci could be suppressed by mutation of nonhomologous-end-joining proteins. Analysis of GFP::RPA-1 revealed fewer foci in the brc-1brd-1 mutant and concentration of BRC-1-BRD-1 to sites of meiotic recombination was dependent on DNA end resection, suggesting that the complex regulates the processing of meiotic double-strand breaks to promote repair by homologous recombination. Further, BRC-1-BRD-1 is important to promote progeny viability when male meiosis is perturbed by mutations that block the pairing and synapsis of different chromosome pairs, although the complex is not required to stabilize the RAD-51 filament as in female meiosis under the same conditions. Analyses of crossover designation and formation revealed that BRC-1-BRD-1 inhibits supernumerary COs when meiosis is perturbed. Together, our findings suggest that BRC-1-BRD-1 regulates different aspects of meiotic recombination in male and female meiosis.

scholarly journals Extensive meiotic asynapsis in mice antagonises meiotic silencing of unsynapsed chromatin and consequently disrupts meiotic sex chromosome inactivation

2008 ◽  
Vol 182 (2) ◽  
pp. 263-276 ◽  
Author(s):  
Shantha K. Mahadevaiah ◽  
Déborah Bourc'his ◽  
Dirk G. de Rooij ◽  
Timothy H. Bestor ◽  
James M.A. Turner ◽  
...  
Keyword(s):  
Sex Chromosome ◽  
Male Meiosis ◽  
Chromosome Inactivation ◽  
Null Mouse ◽  
Dna Double Strand Breaks ◽  
Meiotic Silencing ◽  
Meiotic Sex Chromosome Inactivation ◽  
Y Chromosomes ◽  
Meiotic Dsbs ◽  
Sex Chromosome Inactivation

Chromosome synapsis during zygotene is a prerequisite for the timely homologous recombinational repair of meiotic DNA double-strand breaks (DSBs). Unrepaired DSBs are thought to trigger apoptosis during midpachytene of male meiosis if synapsis fails. An early pachytene response to asynapsis is meiotic silencing of unsynapsed chromatin (MSUC), which, in normal males, silences the X and Y chromosomes (meiotic sex chromosome inactivation [MSCI]). In this study, we show that MSUC occurs in Spo11-null mouse spermatocytes with extensive asynapsis but lacking meiotic DSBs. In contrast, three mutants (Dnmt3l, Msh5, and Dmc1) with high levels of asynapsis and numerous persistent unrepaired DSBs have a severely impaired MSUC response. We suggest that MSUC-related proteins, including the MSUC initiator BRCA1, are sequestered at unrepaired DSBs. All four mutants fail to silence the X and Y chromosomes (MSCI failure), which is sufficient to explain the midpachytene apoptosis. Apoptosis does not occur in mice with a single additional asynapsed chromosome with unrepaired meiotic DSBs and no disturbance of MSCI.

scholarly journals Germ granule-mediated RNA regulation in male germ cells

Reproduction ◽  
2018 ◽  
Vol 155 (2) ◽  
pp. R77-R91 ◽  
Author(s):  
Tiina Lehtiniemi ◽  
Noora Kotaja
Keyword(s):  
Germ Cells ◽  
Posttranscriptional Regulation ◽  
Current Knowledge ◽  
Expression Patterns ◽  
Rna Degradation ◽  
Regulatory Mechanisms ◽  
Rna Regulation ◽  
Male Germ Cells ◽  
Germ Granules ◽  
Rnp Granules

Germ cells have exceptionally diverse transcriptomes. Furthermore, the progress of spermatogenesis is accompanied by dramatic changes in gene expression patterns, the most drastic of them being near-to-complete transcriptional silencing during the final steps of differentiation. Therefore, accurate RNA regulatory mechanisms are critical for normal spermatogenesis. Cytoplasmic germ cell-specific ribonucleoprotein (RNP) granules, known as germ granules, participate in posttranscriptional regulation in developing male germ cells. Particularly, germ granules provide platforms for the PIWI-interacting RNA (piRNA) pathway and appear to be involved both in piRNA biogenesis and piRNA-targeted RNA degradation. Recently, other RNA regulatory mechanisms, such as the nonsense-mediated mRNA decay pathway have also been associated to germ granules providing new exciting insights into the function of germ granules. In this review article, we will summarize our current knowledge on the role of germ granules in the control of mammalian male germ cell’s transcriptome and in the maintenance of fertility.

scholarly journals Dynamic sex chromosome expression in Drosophila male germ cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Sharvani Mahadevaraju ◽  
Justin M. Fear ◽  
Miriam Akeju ◽  
Brian J. Galletta ◽  
Mara M. L. S. Pinheiro ◽  
...  
Keyword(s):  
Rna Polymerase Ii ◽  
Germ Cells ◽  
Sex Chromosomes ◽  
Copy Number ◽  
Defense Mechanism ◽  
Sex Chromosome ◽  
Rna Seq ◽  
Male Germ Cells ◽  
Transcript Levels ◽  
Y Chromosomes

AbstractGiven their copy number differences and unique modes of inheritance, the evolved gene content and expression of sex chromosomes is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4th) that re-acquired autosomal status. Here we use single cell RNA-Seq on fly larvae to demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes, based on measuring all genes or a set of broadly expressed genes in testis we identified. In contrast, genes on the single Y chromosome become maximally active in primary spermatocytes. Reduced X transcript levels are due to failed activation of RNA-Polymerase-II by phosphorylation of Serine 2 and 5.

scholarly journals Dynamic Sex Chromosome Expression in Drosophila Male Germ Cells

2020 ◽  
Author(s):  
Sharvani Mahadevaraju ◽  
Justin M. Fear ◽  
Miriam Akeju ◽  
Brian J. Galletta ◽  
Mara MLS. Pinheiro ◽  
...  
Keyword(s):  
Single Cell ◽  
Rna Polymerase Ii ◽  
Germ Cells ◽  
Defense Mechanism ◽  
Sex Chromosome ◽  
Single Cell Level ◽  
Rna Seq ◽  
Cell Level ◽  
Male Germ Cells ◽  
Y Chromosomes

AbstractSex chromosome gene content and expression is unusual. In many organisms the X and Y chromosomes are inactivated in spermatocytes, possibly as a defense mechanism against insertions into unpaired chromatin. In addition to current sex chromosomes, Drosophila has a small gene-poor X-chromosome relic (4th) that re-acquired autosomal status. Using single cell RNA-Seq, we demonstrate that the single X and pair of 4th chromosomes are specifically inactivated in primary spermatocytes. In contrast, genes on the single Y chromosome become maximally active in primary spermatocytes. Reduced X steady-state transcript levels are due to failed activation of RNA-Polymerase-II by phosphorylation of Serine 2 and 5.One Sentence SummarySex chromosome expression during spermatogenesis at the single cell level

scholarly journals C. elegans BRC-1-BRD-1 functions at an early step of DSB processing and inhibits supernumerary crossovers during male meiosis

2020 ◽  
Author(s):  
Qianyan Li ◽  
Sara Hariri ◽  
JoAnne Engebrecht
Keyword(s):  
Meiotic Recombination ◽  
Sex Chromosome ◽  
Male Meiosis ◽  
Nonhomologous End Joining ◽  
End Joining ◽  
Female Meiosis ◽  
Strand Breaks ◽  
C Elegans ◽  
Meiotic Sex Chromosome Inactivation ◽  
Dna End Resection

AbstractMeiosis is regulated in a sex-specific manner to produce two distinct gametes, sperm and oocytes, for sexual reproduction. To determine how meiotic recombination is regulated in spermatogenesis, we analyzed the meiotic phenotypes of mutants in the tumor suppressor E3 ubiquitin ligase BRC-1-BRD-1 complex in Caenorhabditis elegans male meiosis. Unlike in mammals, this complex is not required for meiotic sex chromosome inactivation, the process whereby hemizygous sex chromosomes are transcriptionally silenced. Interestingly, brc-1 and brd-1 mutants showed meiotic recombination phenotypes that are largely opposing to those previously reported for female meiosis. Fewer meiotic recombination foci marked by the recombinase RAD-51 were observed in brc-1 and brd-1 mutants, and the reduction in RAD-51 foci can be suppressed by mutation of nonhomologous end joining proteins. We show that concentration of BRC-1-BRD-1 to sites of meiotic recombination is dependent on DNA end resection, suggesting that BRC-1-BRD-1 regulates the processing of meiotic double strand breaks to promote repair by homologous recombination, similar to a role for the complex in somatic cells. We also show that BRC-1-BRD-1 is important to promote progeny viability when male meiosis is perturbed by mutations that block the pairing and synapsis of different chromosome pairs, although the complex is not required to stabilize the RAD-51 filament as in female meiosis under the same conditions. Analyses of crossover designation and formation reveal that BRC-1-BRD-1 inhibits supernumerary crossovers when meiosis is perturbed. Together, our findings suggest that BRC-1-BRD-1 regulates different aspects of meiotic recombination in male and female meiosis.

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