p53 and TAp63 participate in the recombination-dependent pachytene arrest in mouse spermatocytes

Area of Science:

• Reproductive biology
• Cellular and molecular biology
• Genetics

Background:

• Meiosis requires precise DNA repair and recombination for genomic stability in germ cells.
• The MRE11 complex-ATM-CHK2 pathway mediates pachytene arrest in response to unrepaired DNA double-strand breaks (DSBs) during mammalian spermatogenesis.
• p53 family members are downstream targets of ATM and CHK2, suggesting potential roles in this surveillance pathway.

Purpose of the Study:

• To investigate the role of p53 family members (p53, TAp63, p73) in the recombination-dependent meiotic arrest of spermatocytes.
• To determine if p53 family members are required for the arrest triggered by Trip13 deficiency.

Main Methods:

• Generation of double-mutant mice combining mutations in p53 family members (p53, TAp63, or p73) with a Trip13 mutation.
• Analysis of spermatocyte progression through meiotic prophase and detection of unrepaired DSBs in mutant mice.
• Assessment of apoptosis and sex body formation in developing spermatocytes.

Main Results:

• Deficiency in either p53 or TAp63, but not p73, allowed spermatocytes with unrepaired DSBs to progress further in meiotic prophase.
• Trip13-deficient spermatocytes lacking p53 or TAp63 still underwent apoptosis at late pachynema due to sex body deficiency.
• These findings demonstrate that recombination-dependent arrest and sex body-deficient arrest are regulated by distinct genetic pathways.

Conclusions:

• p53 and TAp63 are dispensable for the initial meiotic arrest caused by recombination defects and unrepaired DSBs.
• p53 and TAp63 are also dispensable for the later meiotic arrest resulting from sex body defects.
• The study delineates genetically separable mechanisms controlling meiotic arrest during spermatogenesis.