Meiotic Regulation in Mammalian Oocyte Development

Meiotic regulation in mammalian oocytes is a finely tuned process that ensures the faithful reduction of the genome and the generation of a competent egg capable of supporting early embryonic development. Oocytes arrest in prophase I shortly after foetal life and remain dormant until hormonal cues at puberty trigger the resumption of meiosis. Central to this transition are cyclin‐dependent kinases, notably CDK1 in complex with specific cyclins, whose activity is modulated by phosphorylation, dephosphorylation and controlled proteolysis. Concomitantly, epigenetic regulators remodel chromatin to permit accurate chromosome segregation and spindle assembly in the absence of centrioles. Quality control is enforced by the spindle assembly checkpoint, which monitors kinetochore–microtubule attachments and delays anaphase onset until all chromosomes are correctly aligned. Disruption of any component of this network can lead to aneuploidy, arrested maturation or early oocyte attrition, with profound implications for fertility and reproductive lifespan.

Research from Nature Portfolio

Studies have demonstrated that the lysine demethylase LSD1 is indispensable for the timely progression of meiosis I in mouse oocytes: its conditional deletion elevates H3K4 di‐methylation, prematurely upregulates the CDK1‐activating phosphatase CDC25B and precipitates spindle and chromosomal abnormalities, culminating in meiotic arrest and apoptosis. In parallel, investigation of the centrosomal protein Cep55 in acentrosomal oocytes has revealed its localisation to meiotic spindle poles; depletion of Cep55 impairs γ‐tubulin recruitment, activates the spindle assembly checkpoint and prevents first polar body extrusion, underscoring an essential noncanonical role in spindle organisation and metaphase I progression.

Meiotic Regulation in Mammalian Oocyte Development publication trend

The graph below shows the total number of articles in meiotic regulation in mammalian oocyte development across all publications each year (not limited to Nature Index journals).

Technical terms

Meiosis: A specialised cell division that reduces chromosome number by half, generating haploid gametes.

Oocyte: A female germ cell undergoing development to form a mature egg.

Cyclin-dependent kinase 1 (CDK1): A serine/threonine kinase that, in association with cyclins, drives cell cycle transitions.

Cyclin: Regulatory proteins whose periodic synthesis and destruction control CDK activity and cell cycle progression.

Anaphase-promoting complex/cyclosome (APC/C): A ubiquitin ligase that targets cyclins and other proteins for degradation to permit anaphase and exit from mitosis or meiosis.

Spindle assembly checkpoint (SAC): A surveillance mechanism that delays anaphase onset until all chromosomes are properly attached to the spindle.

Germinal vesicle (GV): The oocyte nucleus during prophase I arrest prior to meiotic resumption.

References

1. Meiotic Cell Cycle Progression in Mouse Oocytes: Role of Cyclins. International Journal of Molecular Sciences (2023).
2. Mutations in CCNB3 affect its location thus causing a multiplicity of phenotypes in human oocytes maturation by aberrant CDK1 activity and APC/C activity at different stages. Journal of Ovarian Research (2023).
3. Inhibitory phosphorylation of Cdk1 mediates prolonged prophase I arrest in female germ cells and is essential for female reproductive lifespan. Cell Research (2016).
4. LSD1 is essential for oocyte meiotic progression by regulating CDC25B expression in mice. Nature Communications (2015).
5. Aneuploidy in Oocytes Is Prevented by Sustained CDK1 Activity through Degron Masking in Cyclin B1. Developmental Cell (2019).
6. Cep55 regulates spindle organization and cell cycle progression in meiotic oocyte. Scientific Reports (2015).
7. Translational control of cyclins. Cell Division (2011).