Age-cumulative Effect of REC8 Reduction on Meiotic Chromosome Segregation Errors in Mice

Objective:This study aimed to explore the relationship between cohesin subunit REC8 reduction and meiosis chromosome segregation errors in the ovary.Methods:Rec8^(+/-)mice were generated using CRIPSR/Cas9 gene editing.The association between age and REC8 expression levels in the ovary was determined by Western blotting.Chromosome segregation errors were investigated by immunofluorescence imaging of superovulated oocytes.Wild-type andRec8^(+/-)female mice at 5,8,20,36,and 40 weeks were used to evaluate ovarian reserve by ovarian clearing and immunolabeling.Results:Ovary REC8 expression levels gradually decreased with age,while chromosome segregation errors increased with age.Segregation errors were more common inRec8^(+/-)mice,suggesting an association with REC8 expression.The ovarian reserve capacity decreased significantly with age.The ovarian reserve inRec8^(+/-)mice was inferior to that of age-matched wild-type mice,indicating important roles of age and REC8 levels in the ovarian reserve.Conclusions:REC8 reduction has an age-cumulative effect on meiotic chromosome segregation errors in mouse ovaries.Rec8 haploinsufficiency poses a major challenge in generating normal and reproductive oocytes in aging mice.