英国纽卡斯尔大学等机构研究人员在新一期《当代生物学》（Current Biology）杂志上报告说，现代社会中有越来越多的女性到40岁左右才开始要孩子，由此导致的各种生育问题也日渐增多，研究发现大龄妇女生育易出问题可能与一种蛋白质老化有关。
研究人员对实验鼠在不同年龄时产生卵子的过程进行了对比分析。结果显示，实验鼠体内一种名为黏合素的蛋白质其功能会随年龄增长而逐渐老化。这种蛋白质的作用是将染色体连接在一起，通常体细胞中有两套染色体，而卵子在形成的时候需要黏合素精确地“断开”，以便成为只有一套染色体的生殖细胞。如果黏合素功能失常，就会导致卵子中的染色体数目不正常，从而导致不孕、流产或胎儿缺陷等问题。
领导研究的玛丽·赫伯特博士说，实验中使用的大龄实验鼠年龄约相当于人类的40岁，其体内黏合素的功能已经大幅降低，常导致卵子中染色体数目不正常以及相应的生育问题，这说明黏合素老化可能是人类女性在40岁左右生育能力大幅下降的深层原因，这一发现也有助于从此入手寻找治疗方法。（生物谷Bioon.com）
生物谷推荐英文摘要：
Current Biology doi：10.1016/j.cub.2010.08.023
Age-Related Meiotic Segregation Errors in Mammalian Oocytes Are Preceded by Depletion of Cohesin and Sgo2
Lisa Martine Lister, Anna Kouznetsova, Louise Ann Hyslop, Dimitrios Kalleas, Sarah Louise Pace, Jaclyn Catharina Barel, Abinaya Nathan, Vasileios Floros, Caroline Adelfalk, Yoshinori Watanabe, Rolf Jessberger, Thomas B. Kirkwood, Christer H??g, Mary Herbert
Background
The growing trend for women to postpone childbearing has resulted in a dramatic increase in the incidence of trisomic pregnancies. Maternal age-related miscarriage and birth defects are predominantly a consequence of chromosome segregation errors during the first meiotic division (MI), which involves the segregation of replicated recombined homologous chromosomes. Despite the importance to human reproductive health, the events precipitating female age-related meiotic errors are poorly understood.
Results
Here we use a long-lived wild-type mouse strain to show that the ability to segregate chromosomes synchronously during anaphase of MI declines dramatically during female aging. This is preceded by depletion of chromosome-associated cohesin in association with destabilization of chiasmata, the physical linkages between homologous chromosomes, and loss of the tight association between sister centromeres. Loss of cohesin is not due to an age-related decline in the ability of the spindle checkpoint to delay separase-mediated cleavage of cohesin until entry into anaphase I. However, we find that reduced cohesin is accompanied by depletion of Sgo2, which protects centromeric cohesin during MI.
Conclusions
The data indicate that cohesin declines gradually during the long prophase arrest that precedes MI in female mammals. In aged oocytes, cohesin levels fall below the level required to stabilize chiasmata and to hold sister centromeres tightly together, leading to chromosome missegregation during MI. Cohesin loss may be amplified by a concomitant decline in the levels of the centromeric cohesin protector Sgo2. These findings indicate that cohesin is a key molecular link between female aging and chromosome missegregation during MI.
