Reproduction Abstracts

Introduction: Aneuploidies in mammalian embryos usually originate from oocyte chromosome segregation errors in meiosis I and are a major genetic cause of pregnancy loss. But the mechanism remains poorly understood. We have previously shown total two-cell arrest of IVF embryos derived from superoxide dismutase 1 (SOD1)-deficient mouse oocytes under atmospheric oxygen conditions. This study was conducted to investigate effects of intrinsic oxidative stress by a SOD1 deficiency during in vitro maturation (IVM).

Materials and methods: Immature cumulus–oocyte complexes (COCs) were retrieved from SOD1-deficient and WT ICR mice after administration of equine chorionic gonadotropin (eCG), while IVM COCs were recovered after administration of eCG and human CG. Immature COCs underwent IVM for 18 h under 20 or 5% O₂ culture conditions. The resulted IVM and IVM oocytes were subjected to examination on spindle formation, aneuploidy and expression of BubR1 that is one of the spindle assembly checkpoint (SAC) proteins.

Results and discussion: SOD1-deficient oocytes under 20% O₂ IVM substantially increased chromosome misalignment (45.8%) and a withering spindle assembly compared with WT oocytes or in vivo oocytes (3.3–10%). Under 20% O₂ IVM, SOD1-deficient oocytes accelerated the timing of germinal vesicle break down and progression of anaphase I compared with WT oocytes. The percentage of aneuploidy was two times higher in SOD1-deficient oocytes than in WT oocytes under 20% O₂ IVM while in vivo oocytes showed similar percentage regardless of genotype. BubR1 signals on kinetocore were apparently weaken in SOD1-deficient oocytes compared with WT oocytes. Our results suggest that intrinsic oxidative stress during oocytes meiotic maturation impairs spindle assembly, regular timing of meiosis progression and localization of BubR1, which would consequently lead to aneuploidy.