College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China; College of Veterinary Medicine, Northwest A&F University, Shaanxi, China
Kun-Huan Zhang
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
Si-Le Wu
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
Zhen-Nan Pan
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
Ming-Hong Sun
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
Xiao-Han Li
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
Jia-Qian Ju
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, China
Shi-Ming Luo
Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China
Xiang-Hong Ou
Fertility Preservation Lab, Reproductive Medicine Center, Guangdong Second Provincial General Hospital, Guangzhou, China
During mammalian oocyte meiosis, spindle migration and asymmetric cytokinesis are unique steps for the successful polar body extrusion. The asymmetry defects of oocytes will lead to the failure of fertilization and embryo implantation. In present study, we reported that an actin nucleating factor Formin-like 2 (FMNL2) played critical roles in the regulation of spindle migration and organelle distribution in mouse and porcine oocytes. Our results showed that FMNL2 mainly localized at the oocyte cortex and periphery of spindle. Depletion of FMNL2 led to the failure of polar body extrusion and large polar bodies in oocytes. Live-cell imaging revealed that the spindle failed to migrate to the oocyte cortex, which caused polar body formation defects, and this might be due to the decreased polymerization of cytoplasmic actin by FMNL2 depletion in the oocytes of both mice and pigs. Furthermore, mass spectrometry analysis indicated that FMNL2 was associated with mitochondria and endoplasmic reticulum (ER)-related proteins, and FMNL2 depletion disrupted the function and distribution of mitochondria and ER, showing with decreased mitochondrial membrane potential and the occurrence of ER stress. Microinjecting Fmnl2-EGFP mRNA into FMNL2-depleted oocytes significantly rescued these defects. Thus, our results indicate that FMNL2 is essential for the actin assembly, which further involves into meiotic spindle migration and ER/mitochondria functions in mammalian oocytes.
