Jiang Z-Z, Hu M-W, Wang Z-B, Huang L, Lin F, Qi S-T, Ouyang Y-C, Fan H-Y, Schatten H, Mak T W, Sun Q-Y
1] State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China [2] University of Chinese Academy of Sciences, Beijing 100101, China.
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
Cell Death Dis. 2014 Mar 27;5(3):e1154. doi: 10.1038/cddis.2014.126.
Survivin is the smallest member of the inhibitor of apoptosis protein (IAP) family and acts as a bifunctional protein involved in mitosis regulation and apoptosis inhibition. To identify the physiological role of Survivin in female reproduction, we selectively disrupted Survivin expression in oocytes and granulosa cells (GCs), two major cell types in the ovary, by two different Cre-Loxp conditional knockout systems, and found that both led to defective female fertility. Survivin deletion in oocytes did not affect oocyte growth, viability and ovulation, but caused tetraploid egg production and thus female infertility. Further exploration revealed that Survivin was essential for regulating proper meiotic spindle organization, spindle assembly checkpoint activity, timely metaphase-to-anaphase transition and cytokinesis. Mutant mice with Survivin depleted in GCs showed reduced ovulation and subfertility, caused by defective follicular growth, increased follicular atresia and impaired luteinization. These findings suggest that Survivin has an important role in regulating folliculogenesis and oogenesis in the adult mouse ovary.
生存素是凋亡抑制蛋白（IAP）家族中最小的成员，作为一种双功能蛋白参与有丝分裂调控和凋亡抑制。为了确定生存素在雌性生殖中的生理作用，我们通过两种不同的Cre-Loxp条件性敲除系统，选择性地破坏了卵巢中两种主要细胞类型——卵母细胞和颗粒细胞（GCs）中的生存素表达，发现这两种情况均导致雌性生育能力缺陷。卵母细胞中生存素的缺失不影响卵母细胞的生长、活力和排卵，但会导致四倍体卵子产生，从而导致雌性不育。进一步研究发现，生存素对于调节正常的减数分裂纺锤体组织、纺锤体组装检查点活性、及时的中期到后期转换和胞质分裂至关重要。颗粒细胞中生存素缺失的突变小鼠表现出排卵减少和生育力低下，这是由卵泡生长缺陷、卵泡闭锁增加和黄体化受损所致。这些发现表明，生存素在成年小鼠卵巢中调节卵泡发生和卵子发生方面具有重要作用。
