英國紐卡斯爾大學等機構研究人員在新一期《當代生物學》（Current Biology）雜志上報告說，現(xiàn)代社會中有越來越多的女性到40歲左右才開始要孩子,，由此導致的各種生育問題也日漸增多,，研究發(fā)現(xiàn)大齡婦女生育易出問題可能與一種蛋白質老化有關。
研究人員對實驗鼠在不同年齡時產(chǎn)生卵子的過程進行了對比分析,。結果顯示,，實驗鼠體內一種名為黏合素的蛋白質其功能會隨年齡增長而逐漸老化。這種蛋白質的作用是將染色體連接在一起,，通常體細胞中有兩套染色體,，而卵子在形成的時候需要黏合素精確地“斷開”，以便成為只有一套染色體的生殖細胞,。如果黏合素功能失常,，就會導致卵子中的染色體數(shù)目不正常，從而導致不孕,、流產(chǎn)或胎兒缺陷等問題,。
領導研究的瑪麗·赫伯特博士說，實驗中使用的大齡實驗鼠年齡約相當于人類的40歲,，其體內黏合素的功能已經(jīng)大幅降低,，常導致卵子中染色體數(shù)目不正常以及相應的生育問題，這說明黏合素老化可能是人類女性在40歲左右生育能力大幅下降的深層原因,，這一發(fā)現(xiàn)也有助于從此入手尋找治療方法,。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
