Research finds that REC8 degradation in mouse eggs causes chromosomal abnormalities — Evidence Review
Published in Nature Aging, by researchers from Yale University School of Medicine
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Table of Contents
Scientists at Yale have developed a new method to replicate age-related changes in mouse egg cells, helping to identify how chromosomal errors increase as eggs age. Related studies largely support the finding that loss of chromosome cohesion, particularly involving the protein REC8, is a key driver of aneuploidy in aging eggs, though additional mechanisms may also contribute (1, 2, 6).
- The new study’s focus on REC8 degradation aligns with prior research demonstrating that weakened chromosome cohesion, particularly at the centromere, leads to chromosomal missegregation and increased aneuploidy in both mice and humans (1, 2, 6).
- Related studies further identify that not only cohesion loss but also defects in spindle microtubule dynamics contribute to age-related segregation errors in eggs, suggesting a multifactorial process (3, 5).
- Research into fertility preservation and ovarian rejuvenation is ongoing, with experimental treatments such as platelet-rich plasma and mitochondrial supplementation showing preliminary promise but requiring further validation for effectiveness and safety (8, 9, 11).
Study Overview and Key Findings
Understanding why chromosomal errors in human eggs increase with age is crucial as more women delay childbearing and face higher risks of infertility and genetic disorders. The Yale study addresses a significant gap: the inability to experimentally model aging in eggs without waiting years for animals or humans to age naturally. By employing a CRISPR-based system to control the degradation of the REC8 protein in mouse egg cells, researchers can rapidly induce aging-like chromosomal changes and study their effects.
| Property | Value |
|---|---|
| Study Year | 2023 |
| Organization | Yale University School of Medicine |
| Journal Name | Nature Aging |
| Authors | Binyam Mogessie |
| Population | Mouse egg cells |
| Methods | Animal Study |
| Outcome | Chromosomal abnormalities and aging effects on eggs |
| Results | Degrading REC8 led to errors in chromosome splitting and aneuploidy. |
Literature Review: Related Studies
To place these findings in context, we searched the Consensus research database—which includes over 200 million papers—using targeted queries. The following search queries were used to identify relevant studies:
- aging eggs chromosome errors
- REC8 degradation aneuploidy effects
- fertility rejuvenation techniques research
Below is a summary of key topics and findings from the related studies:
| Topic | Key Findings |
|---|---|
| Why do chromosomal errors in eggs increase with age? | - Loss of chromosome cohesion, especially at centromeres (REC8-related), is a leading cause of age-related aneuploidy in oocytes (1, 2, 6). - Changes in spindle microtubule dynamics and checkpoint sensitivity also contribute (3, 5). |
| What molecular factors underlie cohesion loss and aneuploidy? | - Reduced levels of meiotic cohesin proteins (like REC8) are observed in aged eggs, leading to premature chromatid separation (1, 2, 6). - Loss of centromeric protector proteins (e.g., SGO2) exacerbates cohesion defects (1). |
| Can fertility or egg quality be rejuvenated or preserved? | - Platelet-rich plasma (PRP) injections and mitochondrial supplementation have shown preliminary promise in animal and small human studies, but robust evidence for clinical use is lacking (8, 9, 11). |
| What are the implications for clinical fertility preservation? | - Techniques like ovarian tissue cryopreservation and transplantation are effective in certain settings, but safety and effectiveness for broader rejuvenation remain under investigation (7, 10, 11). |
Why do chromosomal errors in eggs increase with age?
Related studies consistently report that chromosomal errors (aneuploidy) in eggs rise sharply with maternal age, primarily due to deterioration of chromosome cohesion. The Yale study supports this, pinpointing REC8 loss as a central mechanism and providing a precise, controllable model for studying these changes.
- Loss of chromosome cohesion, especially at centromeres, is a leading cause of age-related aneuploidy in both mice and humans (1, 2, 6).
- Spindle assembly checkpoint deficiencies and altered microtubule dynamics further increase the risk of missegregation (3, 5).
- The combination of cohesion loss and other structural changes in chromosomes explains the exponential increase in error rates after age 35 (4, 6).
- The Yale study’s rapid induction of REC8 degradation in mouse eggs provides a new tool to dissect these age-related mechanisms more efficiently (1, 6).
What molecular factors underlie cohesion loss and aneuploidy?
The molecular breakdown of cohesion—specifically involving cohesin proteins like REC8—has been repeatedly implicated in age-related chromosomal errors. The new study’s focus on REC8 degradation aligns with these findings, reinforcing its central role in maintaining chromosomal stability in eggs.
- Aged eggs show reduced levels of REC8, with corresponding increases in chromatid separation and aneuploidy (1, 6).
- Loss of centromeric protector proteins (e.g., SGO2) further destabilizes chromosome cohesion (1).
- Increased inter-kinetochore distance in aged human eggs is a marker of weakened cohesion (2).
- The Yale model enables controlled manipulation of these molecular components, advancing analysis beyond observational studies (6).
Can fertility or egg quality be rejuvenated or preserved?
Several experimental strategies aim to preserve or enhance egg quality, including PRP injections and mitochondrial supplementation. While some case studies and small trials report improvements, conclusive evidence for their effectiveness and safety is still lacking.
- PRP injections into ovaries have led to improved hormone levels and pregnancies in small cohorts, but mechanisms and long-term outcomes remain unclear (8, 11).
- Mitochondrial supplementation has not consistently improved embryo quality in human trials, highlighting the need for further study (9).
- The Yale system could be used to test such interventions in a controlled setting, providing more rigorous evidence for potential treatments (8, 9).
- Ovarian tissue cryopreservation and transplantation are established for fertility preservation in cancer patients, but broader rejuvenative applications are still experimental (7, 10).
What are the implications for clinical fertility preservation?
As more women seek to delay childbearing, clinical demand for fertility preservation and rejuvenation options is rising. Existing techniques like ovarian tissue cryopreservation are effective for specific groups, but broader use for age-related fertility decline requires more research.
- Ovarian tissue cryopreservation and transplantation have resulted in live births post-cancer treatment, but risks and benefits for age-related use are still being evaluated (7, 10).
- Experimental strategies to eliminate cancer risk in preserved tissue are under development, including artificial ovaries and stem cell approaches (10).
- Clinical application of ovarian rejuvenation techniques like PRP remains premature without more robust safety and efficacy data (11).
- The Yale model’s ability to simulate aging-like changes in eggs could facilitate preclinical testing of candidate therapies (10, 11).
Future Research Questions
While the Yale study offers a powerful new approach to modeling egg aging, several important questions remain. Further research is needed to clarify the complex, multifactorial causes of age-related aneuploidy, to validate potential rejuvenation treatments, and to translate findings from mice to humans.
| Research Question | Relevance |
|---|---|
| What other molecular pathways besides REC8 contribute to age-related chromosomal errors in eggs? | Understanding additional pathways is critical for comprehensive models of aneuploidy and could reveal new therapeutic targets beyond cohesion factors (1, 3, 5). |
| Can the Yale model predict human egg aging and therapy responses? | Validating the model’s predictive power for human eggs is essential for translating findings to clinical applications, given species differences in reproductive biology (2, 4, 6). |
| Are combination therapies targeting multiple cohesion and spindle factors more effective at preventing aneuploidy than single-agent approaches? | Since synergistic failures in chromosome separation machinery drive errors, multi-target interventions may offer superior outcomes (3, 5). |
| What are the long-term safety and efficacy outcomes of PRP and mitochondrial supplementation in human IVF? | Early studies are promising but lack long-term follow-up, and thorough evaluation is needed before these treatments can be widely adopted (8, 9, 11). |
| How do lifestyle or environmental factors influence age-related egg cohesion and aneuploidy? | Identifying modifiable risk factors could inform preventive strategies and public health guidance for women delaying childbearing (4, 5). |
This article is for informational purposes only and does not constitute medical advice.