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Updated: Apr 6, 2026
Meiotic Spindle Assessment in Mouse Oocytes by siRNA-mediated Silencing
Published on: October 11, 2015
Functions of the MRE11 complex in the development and maintenance of oocytes
Akiko Inagaki1, Ramon Roset1,2, John H J Petrini3,4
1Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA.
Abstract:
The MRE11 complex (MRE11, RAD50, and NBS1) is a central component of the DNA damage response, governing both double-strand break repair and DNA damage response signaling. To determine the functions of the MRE11 complex in the development and maintenance of oocytes, we analyzed ovarian phenotypes of mice harboring the hypomorphic Mre11 (ATLD1) allele. Mre11 (ATLD1/ATLD1) females exhibited premature oocyte elimination attributable to defects in homologous chromosome pairing and double-strand break repair during meiotic prophase. Other aspects of meiotic progression, including attachment of telomeres to the nuclear envelope and recruitment of RAD21L, a component of the meiotic cohesin complex to the synaptonemal complex, were normal. Unlike Dmc1 (-/-) and Trp13 (Gt/Gt) mice which exhibit comparable defects in double-strand break repair and oocyte depletion by 5 days post-partum, we found that oocyte attrition occurred by 12 weeks in Mre11 (ATLD1/ATLD1) . Disruption of the oocyte checkpoint pathway governed by Chk2 gene further enhanced the survival of Mre11 (ATLD1/ATLD1) follicles. Together our data suggest that the MRE11 complex influences the elimination of oocytes with unrepaired meiotic double-strand breaks post-natally, in addition to its previously described role in double-strand break repair and homologous synapsis during female meiosis.
Insights
The MRE11 complex is crucial for DNA repair and oocyte maintenance. Its dysfunction leads to premature oocyte loss due to meiotic errors, impacting female fertility.
Area of Science:
- Reproductive Biology
- Molecular Biology
- Genetics
Background:
- The MRE11 complex (MRE11, RAD50, NBS1) is vital for DNA damage response, including double-strand break repair.
- Its role in oocyte development and maintenance requires further elucidation.
Purpose of the Study:
- To investigate the function of the MRE11 complex in oocyte development and maintenance.
- To analyze the ovarian phenotype of mice with a hypomorphic Mre11 allele (ATLD1).
Main Methods:
- Analysis of ovarian phenotypes in Mre11 (ATLD1/ATLD1) mice.
- Assessment of meiotic progression, homologous chromosome pairing, and double-strand break repair.
- Investigation of the MRE11 complex's role in oocyte attrition and checkpoint pathways.
Main Results:
- Mre11 (ATLD1/ATLD1) females showed premature oocyte elimination linked to meiotic prophase defects.
- Homologous pairing and synaptonemal complex formation were impaired, but telomere attachment and RAD21L recruitment were normal.
- Oocyte attrition occurred by 12 weeks, later than in other DNA repair-deficient models, and disrupting the Chk2 pathway improved follicle survival.
Conclusions:
- The MRE11 complex is essential for homologous chromosome pairing and double-strand break repair during female meiosis.
- It influences post-natal oocyte elimination, particularly those with unrepaired meiotic double-strand breaks.
- These findings highlight the MRE11 complex's critical role in maintaining female reproductive potential.
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