GO:0007141 male meiosis I: Spermatogenesis Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0007141 (male meiosis I) is the first meiotic division in the male germline, producing haploid secondary spermatocytes from diploid primary spermatocytes.
• Key events include meiotic initiation, prophase I with synapsis and recombination, metaphase I with homolog conjunction, and anaphase I with separase-mediated segregation [1,6,7].
• Epigenetic regulators such as SMARCA5, METTL16, and hnRNPA2B1 are essential for male meiosis I progression and fertility [2,3,8].
• Histone modifications, including lysine lactylation, dynamically change during meiotic prophase I and influence gene expression.
• Drosophila male meiosis I provides a powerful genetic model, revealing unique homolog conjunction mechanisms [5,7].
• Disruption of male meiosis I genes causes azoospermia, oligospermia, and male infertility, making these genes targets for reproductive research [1,3].
Description
Male meiosis I (GO:0007141) is the specialized cell cycle process that produces haploid secondary spermatocytes from diploid primary spermatocytes during spermatogenesis. This process is essential for generating genetically diverse gametes and ensuring faithful chromosome segregation. Errors in male meiosis I lead to aneuploidy, meiotic arrest, and male infertility [1,6]. Understanding the molecular mechanisms of male meiosis I is critical for reproductive biology, developmental genetics, and clinical andrology. Recent studies have identified numerous regulators, including chromatin remodelers, RNA-binding proteins, and epigenetic modifiers, that orchestrate this complex process [2,3,8]. This article synthesizes current knowledge on male meiosis I, focusing on its definition, stages, key genes, regulatory mechanisms, disease relevance, and research methodologies.
male meiosis I At A Glance
| GO ID | GO:0007141 |
|---|---|
| GO term | male meiosis I |
| Ontology | biological_process |
| Synonym | male meiosis I nuclear division |
| Definition | A cell cycle process comprising the steps by which a cell progresses through male meiosis I, the first meiotic division in the male germline. |
| Major function | Production of haploid secondary spermatocytes from diploid primary spermatocytes |
| Key stages | Meiotic initiation, prophase I, metaphase I, anaphase I, telophase I |
| Related processes | Homologous recombination, synapsis, chromosome segregation |
What Is GO:0007141?
Male meiosis I is the first meiotic division in the male germline, comprising the steps by which a diploid primary spermatocyte progresses through meiosis I to yield two haploid secondary spermatocytes. It is a specialized cell cycle process that includes meiotic initiation, prophase I (with homologous chromosome pairing, synapsis, and recombination), metaphase I, anaphase I, and telophase I, followed by cytokinesis [1,6].
Why Is male meiosis I Important in Cell Biology?
Male meiosis I is fundamental for sexual reproduction, as it ensures the halving of chromosome number and the generation of genetic diversity through recombination. Defects in this process cause meiotic arrest, aneuploidy, and male infertility, affecting millions of men worldwide [1,3]. Moreover, understanding male meiosis I provides insights into conserved mechanisms of chromosome segregation and cell cycle regulation, with implications for cancer and developmental disorders.
• Essential for haploid gamete production and fertility.
• Generates genetic diversity via meiotic recombination.
• Prevents aneuploidy by ensuring accurate homolog segregation.
• Dysregulation leads to azoospermia and oligospermia.
• Involves unique chromatin remodeling and epigenetic regulation [2,4].
• Provides a model for studying cell cycle checkpoints and chromosome dynamics [5,7].
• Key genes are potential targets for male contraception.
• Relevant to understanding testicular germ cell tumors.
• Conserved mechanisms inform studies in other species.
• Advances in CRISPR enable functional dissection of meiosis genes [2,3].
What Happens During male meiosis I?
Meiotic Initiation and Prophase I Entry
In simple terms: The cell gets ready to start meiosis and begins the long first phase.
Male meiosis I begins with the differentiation of spermatogonia into primary spermatocytes, which then enter prophase I. This transition is regulated by retinoic acid signaling and the expression of Stra8, which triggers meiotic initiation. During early prophase I, chromosomes condense and homologous chromosomes pair, forming synaptonemal complexes.
Prophase I: Synapsis and Recombination
In simple terms: Homologous chromosomes pair up and exchange genetic material.
Prophase I is subdivided into leptonema, zygonema, pachynema, and diplonema. During zygonema, synapsis occurs with the formation of the synaptonemal complex, mediated by proteins such as SYCP1, SYCP2, and SYCP3. Recombination is initiated by SPO11-induced double-strand breaks, followed by strand invasion and crossover formation [1,3]. METTL16 is required for meiotic sex chromosome inactivation and DSB formation during male meiosis.
Metaphase I: Homolog Conjunction and Spindle Assembly
In simple terms: Paired chromosomes line up in the middle of the cell.
In metaphase I, homologous chromosomes are held together by chiasmata and the synaptonemal complex, and they align at the metaphase plate. In Drosophila male meiosis, homolog conjunction is mediated by the protein UNO, which is cleaved by separase at anaphase I. The spindle assembly checkpoint ensures proper attachment of chromosomes to microtubules.
Anaphase I and Telophase I: Segregation and Cytokinesis
In simple terms: The paired chromosomes separate and the cell divides into two.
At anaphase I, homologous chromosomes are pulled to opposite poles by the spindle apparatus. Separase-mediated cleavage of cohesin and UNO allows sister chromatid separation in preparation for meiosis II. Telophase I follows, and cytokinesis produces two haploid secondary spermatocytes.
Epigenetic Regulation During Male Meiosis I
In simple terms: Chemical tags on DNA and proteins control gene activity during meiosis.
Dynamic changes in histone modifications, such as lysine lactylation, occur during meiotic prophase I and regulate gene expression. SMARCA5 restricts chromatin accessibility to promote male meiosis and fertility. The m6A reader hnRNPA2B1 modulates late pachytene progression through post-transcriptional control.
Key Genes Involved in GO:0007141 male meiosis I
The following genes and proteins are critical for male meiosis I progression, as supported by recent literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| STRA8 | Meiotic initiation | Essential for entry into meiosis |
| SPO11 | Double-strand break formation | Initiates recombination |
| SYCP1 | Synaptonemal complex formation | Required for synapsis |
| SYCP3 | Synaptonemal complex formation | Marker of prophase I |
| SMARCA5 | Chromatin remodeling | Promotes male meiosis and fertility |
| METTL16 | m6A methyltransferase | Required for MSCI and DSB formation |
| hnRNPA2B1 | m6A reader | Modulates late pachytene progression |
| UNO | Homolog conjunction | Drosophila male meiosis I specific |
| Separase | Cohesin cleavage | Required for chromosome separation |
| HORMAD1 | Meiotic chromosome organization | Regulates synapsis and recombination |
| HORMAD2 | Meiotic chromosome organization | Regulates synapsis and recombination |
| DMC1 | Meiotic recombinase | Catalyzes strand invasion |
| RAD51 | Meiotic recombinase | Catalyzes strand invasion |
| MLH1 | Crossover formation | Mismatch repair protein |
| MLH3 | Crossover formation | Mismatch repair protein |
| TEX11 | Crossover formation | Regulates recombination |
| BRCA2 | Recombination mediator | Loads RAD51 |
How Is male meiosis I Regulated?
Male meiosis I is regulated by a complex network of transcription factors, signaling pathways, and epigenetic modifiers. Retinoic acid signaling activates Stra8, which is essential for meiotic initiation. The chromatin remodeler SMARCA5 restricts chromatin accessibility to promote male meiosis. METTL16, an m6A methyltransferase, is required for meiotic sex chromosome inactivation and DSB formation. The m6A reader hnRNPA2B1 modulates late pachytene progression through post-transcriptional control. Additionally, dynamic histone lactylation during prophase I influences gene expression. These regulatory layers ensure the timely progression and fidelity of male meiosis I.
male meiosis I and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SYCP3 | Azoospermia | Knockout mouse |
| TEX11 | Meiotic arrest | Knockout mouse |
| MLH3 | Male infertility | Point mutation knock-in |
| METTL16 | Impaired MSCI and DSB | Conditional knockout mouse |
| SMARCA5 | Meiotic arrest | Knockout mouse |
Male Infertility
Disruption of male meiosis I genes causes meiotic arrest, leading to azoospermia or oligospermia and male infertility [1,3]. Mutations in genes such as SYCP3, TEX11, and MLH3 have been associated with human spermatogenic failure. METTL16 deficiency impairs meiotic sex chromosome inactivation and DSB formation, resulting in infertility in mouse models.
Aneuploidy and Birth Defects
Errors in chromosome segregation during male meiosis I can produce aneuploid sperm, contributing to trisomy syndromes such as Klinefelter syndrome (47,XXY) and Down syndrome (trisomy 21). Proper homolog conjunction and spindle assembly checkpoint control are critical to prevent aneuploidy [6,7].
Testicular Germ Cell Tumors
Aberrant expression of meiosis-specific genes, including those involved in male meiosis I, has been observed in testicular germ cell tumors. Understanding the regulation of male meiosis I may provide insights into the origin and progression of these tumors.
From male meiosis I-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate meiotic initiation? | Knockout mouse (Stra8, etc.) |
| Does a point mutation in gene Y affect recombination? | Point mutation knock-in mouse |
| Does overexpression of gene Z rescue meiosis? | Transgenic overexpression mouse |
| Where is protein X localized during meiosis I? | Tagged knock-in (e.g., GFP) mouse |
| What is the role of gene W in chromatin accessibility? | Conditional knockout (SMARCA5) |
| How does m6A modification affect pachytene progression? | METTL16 knockout and hnRNPA2B1 knockout |
How to Study the male meiosis I Process
| Method | What It Measures | Typical Application |
|---|---|---|
| RNA-seq | Gene expression | Identify meiosis-specific transcripts |
| scRNA-seq | Single-cell transcriptomes | Dissect stage-specific regulation |
| ATAC-seq | Chromatin accessibility | Study SMARCA5 function |
| ChIP-seq | Histone modifications | Map lactylation and methylation |
| Proteomics | Protein abundance and modifications | Discover interaction networks |
| Immunofluorescence | Protein localization | Assess synapsis and recombination |
| Live-cell imaging | Chromosome dynamics | Monitor segregation in real time |
Transcriptomics and Single-Cell RNA Sequencing
RNA-seq and scRNA-seq can profile gene expression changes during male meiosis I, identifying stage-specific transcripts and alternative splicing events [1,8]. These methods are useful for discovering novel regulators and validating knockout phenotypes.
Epigenomic Profiling
ATAC-seq, ChIP-seq, and bisulfite sequencing measure chromatin accessibility, histone modifications, and DNA methylation during male meiosis I [2,4]. These techniques reveal dynamic epigenetic changes, such as histone lactylation and m6A modifications [3,4].
Proteomics and Post-Translational Modification Analysis
Mass spectrometry-based proteomics can identify protein interactions and post-translational modifications, such as lactylation and phosphorylation, during meiosis I. This approach helps elucidate signaling pathways and regulatory networks.
Imaging and Cytogenetics
Immunofluorescence and live-cell imaging with markers such as SYCP3 and MLH1 allow visualization of synapsis, recombination, and chromosome segregation [1,5]. These methods are essential for assessing meiotic defects in mutant models.
How CRISPR Can Be Used to Study GO:0007141 male meiosis I
Knockout
CRISPR knockout of male meiosis I genes in mouse models or cell lines can reveal essential functions. For example, Smarca5 knockout causes meiotic arrest and infertility, while Mettl16 knockout impairs meiotic sex chromosome inactivation and DSB formation. These models are valuable for studying gene function in vivo.
Point Mutation
Point mutations can mimic human disease variants or disrupt specific protein domains. For instance, introducing a point mutation in the separase cleavage site of UNO in Drosophila can block homolog separation. Such models help dissect domain-specific functions.
Knock-in
Knock-in of tagged proteins (e.g., GFP, HA) allows visualization and biochemical purification of meiotic proteins. Tagged SYCP3 or MLH1 knock-in mice enable live imaging of synapsis and crossover formation. Knock-in of reporter genes can also track meiotic stage-specific expression.
Overexpression
Overexpression of male meiosis I genes can test sufficiency or rescue phenotypes. For example, overexpression of hnRNPA2B1 may rescue late pachytene defects in knockout models. Transgenic overexpression in mouse testes can be achieved via CRISPR-mediated knock-in of a strong promoter.
How EDITGENE Supports male meiosis I Research
Researchers studying male meiosis I-related genes often need to determine whether a candidate gene is causally involved in meiotic progression, fertility, or disease. EDITGENE provides comprehensive CRISPR-based services to accelerate functional genomics in reproductive biology.
Contact EDITGENE today to design your custom CRISPR model for male meiosis I research.
Frequently Asked Questions About male meiosis I
What is male meiosis I (GO:0007141)?
Male meiosis I is the first meiotic division in the male germline, producing haploid secondary spermatocytes from diploid primary spermatocytes.
What genes are involved in male meiosis I?
Key genes include STRA8, SPO11, SYCP1, SYCP3, SMARCA5, METTL16, and hnRNPA2B1, among others [1,2,3,8].
How does male meiosis I differ from female meiosis I?
Male meiosis I is continuous and produces four sperm, while female meiosis I is arrested at prophase I until ovulation and produces one egg and polar bodies.
What are the stages of male meiosis I?
The stages are meiotic initiation, prophase I (leptonema, zygonema, pachynema, diplonema), metaphase I, anaphase I, and telophase I [1,6].
What causes meiotic arrest in male meiosis I?
Mutations in genes such as SYCP3, TEX11, and METTL16 can cause meiotic arrest, leading to azoospermia [1,3].
How is male meiosis I regulated epigenetically?
Epigenetic regulation includes histone lactylation, m6A RNA methylation, and chromatin remodeling by SMARCA5 [2,3,4].
What research methods are used to study male meiosis I?
Common methods include RNA-seq, scRNA-seq, ATAC-seq, ChIP-seq, proteomics, and immunofluorescence [1,2,4].
Can CRISPR be used to study male meiosis I?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect gene function in male meiosis I [2,3,7].
What diseases are linked to male meiosis I defects?
Defects are linked to male infertility, aneuploidy, and testicular germ cell tumors [1,3,6].
What is the role of SMARCA5 in male meiosis I?
SMARCA5 restricts chromatin accessibility to promote male meiosis and fertility.
Conclusion
Male meiosis I (GO:0007141) is a tightly regulated process essential for spermatogenesis and fertility. Recent advances have uncovered critical roles for chromatin remodelers, RNA modifiers, and epigenetic marks in ensuring proper meiotic progression [1,2,3,4,8]. Dysregulation of these pathways leads to meiotic arrest and male infertility, highlighting the clinical importance of this process [1,3]. Continued research using CRISPR models and multi-omics approaches will further elucidate the molecular logic of male meiosis I and inform therapeutic strategies for reproductive disorders.
References
- 1. Ishiguro KI. 2024. Mechanisms of meiosis initiation and meiotic prophase progression during spermatogenesis.. Mol Aspects Med 97:101282 PMID: 38797021
- 2. 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
- 3. Yin L et al.. 2025. METTL16 is Required for Meiotic Sex Chromosome Inactivation and DSB Formation and Recombination during Male Meiosis.. Adv Sci (Weinh) 12(3):e2406332 PMID: 39607422
- 4. Zhang X et al.. 2025. Dynamic changes in histone lysine lactylation during meiosis prophase I in mouse spermatogenesis.. Proc Natl Acad Sci U S A 122(7):e2418693122 PMID: 39928879
- 5. Bonaccorsi S et al.. 2017. Drosophila Male Meiosis.. Methods Mol Biol 1471:277-288 PMID: 28349403
- 6. Zhang X et al.. 2026. Orchestrating homolog segregation in meiosis I: molecular logic and regulatory networks with emphasis on male metaphase I.. Cell Commun Signal 24(1) PMID: 41827022
- 7. Weber J et al.. 2020. Chromosome separation during Drosophila male meiosis I requires separase-mediated cleavage of the homolog conjunction protein UNO.. PLoS Genet 16(10):e1008928 PMID: 33001976
- 8. Yin L et al.. 2025. m(6)A Reader hnRNPA2B1 Modulates Late Pachytene Progression in Male Meiosis Through Post-Transcriptional Control.. Adv Sci (Weinh) 12(38):e06600 PMID: 40720760
