(Peer-Reviewed) Age-cumulative effect of REC8 reduction on meiotic chromosome segregation errors in mice
Li-Yuan Tian ¹, Ling Zhang 张玲 ¹, Cheng-Qiu Tao ², Xiao-Qi Lin ², Feng Zhang 张锋 ¹ ², Bin Zhang 张斌 ¹
¹ Department of Obstetrics, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China
中国 上海 复旦大学附属妇产科医院妇产科
² Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai 200011, China
中国 上海 上海市女性生殖内分泌相关疾病重点实验室
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 and Rec8+/− 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 in Rec8+/− mice, suggesting an association with REC8 expression. The ovarian reserve capacity decreased significantly with age. The ovarian reserve in Rec8+/− 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.
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