MRE11 orchestrates porcine oocyte meiotic progression by modulating the spindle assembly checkpoint

Dandan Zhang¹Zaishan Yang²ZHANG Yongteng²Fugui Fang²Hongguo Cao²Yunsheng Li²Zubing Cao²Yanfeng Xue²Mianqun Zhang^2*

• ¹Department of Reproductive Medicine, General Hospital of WanBei Coal Group, SuZhou, 234000, China, Wanbei Coal and Power Group General Hospital, Suzhou, Anhui Province, China
• ²Anhui Province Key Laboratory of Local Livestock and Poultry Genetical Resource Conservation and Breeding, College of Animal Science and Technology, Anhui Agricultural University, Hefei, 230036, China, Anhui Agricultural University, Hefei, China

Mre11 is a multisubunit nuclease, and its dysfunction often leads to DNA damage sensitivity, genomic instability, telomere shortening, and aberrant meiosis. However, its functional roles in porcine oocyte meiosis have not yet been fully elucidated. In the present study, we applied the Mre11-specific inhibitor mirin in porcine oocytes, validating the roles of Mre11 during mammalian oocyte maturation. We demonstrated that inhibition of Mre11 activity led to the failure of first polar body extrusion, accompanied by the presence of BubR1 at kinetochores. In addition, spindle/chromosome structure was disrupted in Mre11-inhibited oocytes due to the weakened microtubule stability, which is a major cause resulting in the activation of SAC. Additionally, the spindle was unable to migrate to the oocyte cortex, leading to defects in polar body formation. This issue may be attributed to reduced cytoplasmic actin polymerization resulting from MRE11 depletion in porcine oocytes. Last, we found that the level DNA damage as assessed by γH2A.X staining was considerably elevated when MRE11 was inhibited, suggesting that DNA damage might be another critical factor leading to the meiotic failure of oocytes. Collectively, our data demonstrate that Mre11 participates in the porcine oocyte meiotic progression through ensuring normal spindle assembly and SAC activity.