GO:0007140 male meiotic nuclear division: Spermatogenesis Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0007140 male meiotic nuclear division is the cell cycle process by which the nucleus divides during meiosis specifically in the male germline.
• It encompasses two consecutive nuclear divisions, meiosis I and meiosis II, that produce four haploid spermatids from one diploid spermatocyte.
• Key molecular drivers include cohesin complexes (STAG3), chromatin remodelers (SMARCA5), and testis-specific transcription factors such as HSF5.
• Defects in male meiotic nuclear division cause azoospermia, oligozoospermia, and macronuclear spermatozoa in humans.
• Y-chromosome genes have been systematically mapped to specific meiotic steps using mouse knockout resources.
• CRISPR knockout, point-mutation, and knock-in models are essential for dissecting gene function in male meiosis.
Description
Male meiotic nuclear division (GO:0007140) is the specialized cell cycle process by which a diploid male germ cell undergoes two successive nuclear divisions to produce four haploid spermatids. This process is fundamental to sexual reproduction, ensuring the halving of chromosome number and the generation of genetic diversity through recombination. In mammals, male meiotic nuclear division is tightly coordinated with spermatogenesis, and its disruption leads to infertility. Understanding the molecular mechanisms of this process is critical for reproductive biology, evolutionary genetics, and clinical andrology. Recent studies have identified numerous genes essential for male meiotic progression, including chromatin remodelers, cohesin subunits, and transcription factors. The systematic analysis of Y-chromosome genes in mouse models has further revealed stage-specific requirements during male meiosis. This article synthesizes current knowledge on GO:0007140, covering its definition, molecular players, disease relevance, and research methodologies.
male meiotic nuclear division At A Glance
| GO ID | GO:0007140 |
|---|---|
| GO term | male meiotic nuclear division |
| Ontology | biological_process |
| Synonym | male meiosis, male nuclear division |
| Major function | Nuclear division during meiosis in the male germline, producing haploid gametes |
| Related processes | Spermatogenesis, meiotic recombination, chromosome segregation |
| Cellular location | Nucleus of male germ cells |
| Key regulators | STAG3, SMARCA5, HSF5, Y-chromosome genes |
What Is GO:0007140?
GO:0007140 male meiotic nuclear division is defined as a cell cycle process by which the cell nucleus divides as part of a meiotic cell cycle in the male germline. It includes the two meiotic divisions (meiosis I and meiosis II) that occur during spermatogenesis, leading to the formation of haploid spermatids. This term is a biological process and is synonymous with male meiosis and male nuclear division.
Why Is male meiotic nuclear division Important in Cell Biology?
Male meiotic nuclear division is essential for fertility and genetic diversity. Errors in this process lead to aneuploidy, sperm DNA damage, and male infertility. It is also a hotspot for meiotic drive elements that can cause reproductive isolation and speciation. Understanding the genetic control of male meiosis provides insights into evolutionary mechanisms and offers targets for contraception and infertility treatments.
• Ensures haploid gamete production for sexual reproduction.
• Generates genetic diversity through recombination and independent assortment.
• Defects cause azoospermia and oligozoospermia in humans.
• Meiotic drive in male meiosis can drive speciation.
• Y-chromosome genes are critical for male meiotic progression.
• Chromatin remodeling is required for meiotic prophase.
• Cohesin complexes maintain chromosome structure during meiosis.
• Heat shock factors regulate meiotic gene expression.
• Provides targets for male contraception.
• Model organisms like Drosophila inform conserved mechanisms.
What Happens During male meiotic nuclear division?
Meiosis Initiation and Prophase I
In simple terms: The germ cell starts the special two-step division by preparing and recombining its chromosomes.
Male meiotic nuclear division begins with the commitment of spermatogonia to meiosis, marked by retinoic acid signaling and expression of Stra8. During prophase I, homologous chromosomes pair, synapse, and undergo reciprocal recombination, forming crossovers that are essential for proper segregation. This phase is regulated by testis-specific transcription factors such as HSF5, which is critical for male meiotic prophase under non-stress conditions.
Meiosis I Nuclear Division
In simple terms: The first division separates homologous chromosomes into two new nuclei.
In meiosis I, homologous chromosomes are segregated reductionally, requiring the cohesin complex to hold sister chromatids together until anaphase I. The mitotic STAG3-cohesin complex shapes the male germline nucleome and is essential for this division. Errors in meiosis I lead to macronuclear spermatozoa, a phenotype associated with male meiotic division deficiency.
Meiosis II Nuclear Division
In simple terms: The second division separates sister chromatids, resulting in four haploid nuclei.
Meiosis II resembles mitosis but lacks an S phase, and it separates sister chromatids to produce four haploid spermatids. This step requires the same core cell cycle machinery but is specialized for the male germline. Defects in meiosis II also contribute to abnormal sperm morphology.
Chromatin Remodeling and Nuclear Organization
In simple terms: The DNA packaging changes dramatically to allow chromosome movements and compaction.
SMARCA5, a chromatin remodeler, restricts chromatin accessibility to promote male meiosis and fertility in mammals. The cohesin complex further organizes the nucleome during male meiosis. These structural changes are necessary for proper chromosome segregation and for the transition to spermatids.
Cytokinesis and Spermatid Formation
In simple terms: The cell physically splits into four sperm precursor cells.
Following the two nuclear divisions, cytokinesis yields four haploid spermatids that undergo spermiogenesis. This step is coupled to the nuclear divisions and requires precise regulation of the cytoskeleton and membrane dynamics. Failure leads to incomplete division and abnormal sperm.
Key Genes Involved in GO:0007140 male meiotic nuclear division
The following genes have been experimentally implicated in male meiotic nuclear division, based on knockout, knockdown, and genetic studies in model organisms and humans.
| Gene | Major Role | Research Relevance |
|---|---|---|
| STAG3 | Cohesin subunit; maintains sister chromatid cohesion | Knockout causes meiotic arrest and infertility |
| SMARCA5 | Chromatin remodeler; restricts chromatin accessibility | Essential for male meiosis and fertility |
| HSF5 | Heat shock transcription factor; regulates prophase I genes | Critical for male meiotic prophase |
| Stra8 | Retinoic acid-responsive gene; initiates meiosis | Knockout blocks meiotic initiation |
| DMC1 | Meiotic recombinase; catalyzes strand invasion | Required for crossover formation |
| SYCP1 | Synaptonemal complex protein; mediates synapsis | Knockout leads to meiotic arrest |
| SYCP3 | Synaptonemal complex protein; axial element | Knockout causes meiotic defects |
| REC8 | Meiosis-specific cohesin; sister chromatid cohesion | Essential for meiosis I |
| SMC1B | Meiosis-specific cohesin subunit | Required for chromosome segregation |
| TEX11 | Meiotic protein; crossover formation | Mutations associated with azoospermia |
| MLH1 | Mismatch repair protein; crossover marker | Defects linked to meiotic errors |
| MLH3 | Mismatch repair protein; crossover formation | Required for normal meiosis |
| HORMAD1 | Meiotic chromosome axis protein | Regulates synapsis and recombination |
| HORMAD2 | Meiotic chromosome axis protein | Involved in checkpoint control |
| USP26 | Y-chromosome gene; deubiquitinase | Associated with spermatogenic failure |
| DAZ1 | Y-chromosome gene; RNA-binding protein | Deletions cause azoospermia |
| RBMY1 | Y-chromosome gene; RNA-binding protein | Required for spermatogenesis |
How Is male meiotic nuclear division Regulated?
Male meiotic nuclear division is regulated at multiple levels. Transcriptional control by retinoic acid and Stra8 initiates meiosis. Chromatin remodeling by SMARCA5 restricts accessibility to promote meiosis. Heat shock factor HSF5 regulates prophase I gene expression under non-stress conditions. Cohesin complexes and their regulators ensure proper chromosome segregation. Additionally, meiotic drive elements can distort segregation ratios, influencing speciation.
male meiotic nuclear division and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| TEX11 | Azoospermia | Knockout mouse, patient-derived iPSCs |
| DAZ1 | Spermatogenic failure | Y-chromosome deletion mouse models |
| USP26 | Sertoli cell-only syndrome | Knockout mouse, overexpression cell lines |
| STAG3 | Premature ovarian failure and male infertility | Conditional knockout mouse |
| SMARCA5 | Male infertility | Germline-specific knockout mouse |
Male Infertility and Azoospermia
Defects in male meiotic nuclear division are a major cause of azoospermia and oligozoospermia. The phenotype of macronuclear spermatozoa is specifically linked to meiotic division deficiency. Mutations in genes such as TEX11 and Y-chromosome genes like DAZ1 and USP26 are associated with spermatogenic failure.
Meiotic Drive and Speciation
Meiotic drive in male meiosis can cause biased transmission of chromosomes, leading to reproductive isolation and speciation. This evolutionary mechanism highlights the importance of understanding male meiotic nuclear division in natural populations.
Chromosome Aneuploidy
Errors in meiotic chromosome segregation result in aneuploid sperm, which can lead to miscarriage or genetic disorders such as Klinefelter syndrome. Proper cohesin function and recombination are essential to prevent aneuploidy.
From male meiotic nuclear division-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is gene X required for meiosis I? | Knockout mouse or CRISPR KO cell line |
| Does mutation Y affect crossover frequency? | Point-mutation knock-in mouse |
| Where is protein Z localized during meiosis? | Tagged knock-in (e.g., GFP) mouse |
| Can overexpression rescue fertility? | Transgenic overexpression mouse |
| What are the transcriptomic changes? | RNA-seq of sorted germ cells |
| Which Y-chromosome genes are essential? | Systematic Y-gene knockout panel |
How to Study the male meiotic nuclear division Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Gene essentiality | Identifying meiotic genes |
| RNA-seq | Transcriptome changes | Stage-specific expression |
| Single-cell RNA-seq | Cell-to-cell variability | Germ cell heterogeneity |
| Immunofluorescence | Protein localization | Synapsis and recombination |
| ChIP-seq | Chromatin occupancy | Cohesin binding sites |
| Proteomics | Protein interactions | Complex composition |
| Live imaging | Nuclear division dynamics | Meiotic progression |
Genetic Knockout Models
CRISPR/Cas9-mediated knockout in mice or cell lines is the gold standard to test gene essentiality in male meiotic nuclear division. Conditional knockouts using germline-specific Cre drivers avoid lethality and allow stage-specific analysis.
Transcriptomics and Single-Cell RNA-seq
RNA-seq of purified spermatocytes at different stages reveals dynamic gene expression during meiosis. Single-cell RNA-seq can resolve heterogeneity within the germline and identify rare meiotic defects.
Imaging and Cytogenetics
Immunofluorescence of meiotic chromosome spreads visualizes synapsis, recombination foci, and chromosome segregation. Live-cell imaging in Drosophila and mouse models tracks nuclear division dynamics.
Proteomics and Interactomics
Affinity purification coupled to mass spectrometry identifies cohesin and chromatin remodeler complexes in meiotic cells. Phosphoproteomics can reveal signaling pathways regulating meiotic progression.
How CRISPR Can Be Used to Study GO:0007140 male meiotic nuclear division
Knockout
CRISPR knockout of candidate genes in mouse models or spermatogonial stem cell lines is used to assess loss-of-function phenotypes in male meiotic nuclear division. This approach has been applied to Y-chromosome genes systematically.
Point Mutation
Point mutations can be introduced to model human variants associated with infertility or to dissect domain-specific functions of meiotic proteins. This is particularly useful for genes with pleiotropic roles.
Knock-in
Knock-in of tagged versions (e.g., GFP, HA) allows visualization and biochemical purification of meiotic proteins. Knock-in of human disease alleles into mouse models can validate pathogenicity.
Overexpression
Overexpression of meiotic regulators can test sufficiency for meiotic progression or rescue of knockout phenotypes. It is also used to study meiotic drive elements.
How EDITGENE Supports male meiotic nuclear division Research
Researchers studying male meiotic nuclear division-related genes often need to determine whether a candidate gene is causally involved in meiotic progression, chromosome segregation, or fertility. EDITGENE provides comprehensive CRISPR services to accelerate this discovery.
Contact EDITGENE today to design your custom CRISPR model for male meiotic nuclear division research.
Frequently Asked Questions About male meiotic nuclear division
What is male meiotic nuclear division?
It is the cell cycle process by which the nucleus divides during meiosis in the male germline, producing haploid spermatids.
What genes are involved in male meiotic nuclear division?
Key genes include STAG3, SMARCA5, HSF5, Stra8, DMC1, SYCP1, SYCP3, REC8, SMC1B, TEX11, and Y-chromosome genes like DAZ1 and USP26.
What is the GO ID for male meiotic nuclear division?
The GO ID is GO:0007140.
How does male meiotic nuclear division differ from mitosis?
It involves two consecutive divisions without DNA replication between them, producing four haploid cells instead of two diploid cells.
What diseases are linked to defects in male meiotic nuclear division?
Defects cause azoospermia, oligozoospermia, macronuclear spermatozoa, and aneuploidy.
Which model organisms are used to study male meiosis?
Mouse, Drosophila, and yeast are common models, with Drosophila offering powerful genetic tools.
What is the role of cohesin in male meiosis?
Cohesin complexes, including STAG3 and REC8, maintain sister chromatid cohesion and shape the nucleome during male meiosis.
How can CRISPR help study male meiotic nuclear division?
CRISPR enables knockout, point mutation, knock-in, and overexpression models to test gene function in meiosis.
What is macronuclear spermatozoa?
It is a sperm phenotype with enlarged nuclei, associated with meiotic division deficiency and male infertility.
What is meiotic drive?
Meiotic drive is a phenomenon where certain alleles are transmitted more frequently than expected, often involving male meiosis, and can drive speciation.
Conclusion
Male meiotic nuclear division (GO:0007140) is a fundamental biological process required for fertility and genetic diversity. Recent advances have identified critical genes and regulatory mechanisms, from cohesin complexes to chromatin remodelers and transcription factors. Understanding these pathways has direct implications for diagnosing and treating male infertility and for understanding evolutionary processes like meiotic drive. Continued research using CRISPR models and multi-omics approaches will further illuminate this complex process.
References
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- 3. Searle JB et al.. 2024. Meiotic Drive and Speciation.. Annu Rev Genet 58(1):341-363 PMID: 39585909
- 4. Kataruka S et al.. 2025. SMARCA5 restricts chromatin accessibility to promote male meiosis and fertility in mammals.. Proc Natl Acad Sci U S A 122(31):e2422356122 PMID: 40743397
- 5. Yoshimura S et al.. 2024. Atypical heat shock transcription factor HSF5 is critical for male meiotic prophase under non-stress conditions.. Nat Commun 15(1):3330 PMID: 38684656
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