STUDY QUESTION Is CDC26 a key factor in human oocyte aging? SUMMARY ANSWER The lack of CDC26 disrupts the oocytes maturation process, leading to oocyte aging, but these defects could be partially rescued by overexpression of the CDC26 protein. WHAT IS KNOWN ALREADY Age-related oocyte aging is the main cause of female fertility decline. In mammalian oocytes, aberrant meiosis can cause chromosomal abnormalities that might lead to infertility and developmental disorders. CDC26 participates in the meiosis process. STUDY DESIGN, SIZE, DURATION Differential gene expression in young and old women oocytes were screened by single-cell RNA-seq technology, and the functions of differentially genes were verified on mouse oocytes. Finally, transfection technology was used to evaluate the effect of a differentially expressed gene in rescuing human oocyte from aging. PARTICIPANTS/MATERIALS, SETTING, METHODS Discarded human oocytes were collected for single-cell RNA-seq, q-PCR and immunocytochemical analyses to screen for and identify differential gene expression. Female KM mice oocytes were collected for IVM of oocytes, q-PCR and immunocytochemical analyses to delineate the relationships between oocyte aging and differential gene expression. Additionally, recombinant lentiviral vectors encoding CDC26 were transfected into the germinal vesicle oocytes of older women, to investigate the effects of the CDC26 gene expression on oocyte development. MAIN RESULTS AND THE ROLE OF CHANCE Many genes were found to be differentially expressed in the oocytes of young versus old patients via RNA-seq technology. CDC26 mRNA and protein levels in aged oocytes were severely decreased, when compared with the levels observed in young oocytes. Moreover, aged oocytes lacking CDC26 were more prone to aneuploidy. These defects in aged oocytes could be partially rescued by overexpression of the CDC26 protein. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION Our study delineated key steps in the oocyte aging process by identifying the key role of CDC26 in the progression of oocyte maturation. Future studies are required to address whether other signaling pathways play a role in regulating oocyte maturation via CDC26 and which genes are the direct molecular targets of CDC26. WIDER IMPLICATIONS OF THE FINDINGS Our results using in vitro systems for both mouse and human oocyte maturation provide a proof of principle that CDC26 may represent a novel therapeutic approach against maternal aging-related spindle and chromosomal abnormalities. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by grants from the National Natural Science Foundation of China (81571442 and 81170571), the outstanding Talent Project of Shanghai Municipal Commission of Health (XBR2011067) and Clinical Research and Cultivation Project in Shanghai Municipal Hospitals (SHDC12019X32). The authors declare no conflict of interest.

中文翻译：

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CDC26是人类卵母细胞衰老的关键因素

研究问题 CDC26 是人类卵母细胞衰老的关键因素吗？总结答案 CDC26 的缺乏会破坏卵母细胞的成熟过程，导致卵母细胞老化，但这些缺陷可以通过 CDC26 蛋白的过表达来部分挽救。已知情况 与年龄相关的卵母细胞老化是女性生育能力下降的主要原因。在哺乳动物卵母细胞中，异常减数分裂会导致染色体异常，从而导致不育和发育障碍。CDC26 参与减数分裂过程。研究设计、大小、持续时间通过单细胞RNA-seq技术筛选年轻和老年女性卵母细胞的差异基因表达，并在小鼠卵母细胞上验证差异基因的功能。最后，转染技术用于评估差异表达基因在拯救人类卵母细胞免于衰老中的作用。参与者/材料、设置、方法收集废弃的人类卵母细胞进行单细胞 RNA-seq、q-PCR 和免疫细胞化学分析，以筛选和鉴定差异基因表达。收集雌性 KM 小鼠卵母细胞用于卵母细胞的 IVM、q-PCR 和免疫细胞化学分析，以描绘卵母细胞衰老与差异基因表达之间的关系。此外，将编码 CDC26 的重组慢病毒载体转染到老年女性的生泡卵母细胞中，以研究 CDC26 基因表达对卵母细胞发育的影响。主要结果和机会的作用 通过 RNA-seq 技术发现许多基因在年轻和老年患者的卵母细胞中存在差异表达。与年轻卵母细胞中观察到的水平相比，老年卵母细胞中 CDC26 mRNA 和蛋白质水平严重下降。此外，缺乏 CDC26 的老年卵母细胞更容易出现非整倍体。衰老卵母细胞中的这些缺陷可以通过 CDC26 蛋白的过表达来部分挽救。大规模数据 不适用。限制和谨慎的原因 我们的研究通过确定 CDC26 在卵母细胞成熟进程中的关键作用，描绘了卵母细胞衰老过程中的关键步骤。未来的研究需要解决其他信号通路是否在通过 CDC26 调节卵母细胞成熟中发挥作用，以及哪些基因是 CDC26 的直接分子靶点。研究结果的更广泛意义 我们使用体外系统进行小鼠和人类卵母细胞成熟的结果提供了原理证明，即 CDC26 可能代表一种针对母体衰老相关纺锤体和染色体异常的新治疗方法。研究资助/竞争兴趣(S) 这项工作得到了国家自然科学基金 (81571442 和 81170571)、上海市卫健委杰出人才项目 (XBR2011067) 和上海市临床研究与培养项目的资助医院 (SHDC12019X32)。作者宣称没有利益冲突。