Age-related decrease of meiotic cohesins in human oocytes.
Age-related decrease of meiotic cohesins in human oocytes.
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DOI：
10.1371/journal.pone.0096710
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Kurahashi H
中科院分区：
文献类型：
--
作者：
Tsutsumi M;Fujiwara R;Nishizawa H;Ito M;Kogo H;Inagaki H;Ohye T;Kato T;Fujii T;Kurahashi H
胎儿染色体非整倍体是导致流产和先天性出生缺陷的原因之一。已知卵母细胞非整倍体的频率随着人类母亲年龄的增加而增加。最近的数据强调了粘着蛋白复合物在减数分裂染色体正确分离中的作用。在哺乳动物卵母细胞中，凝聚力是在胎儿阶段建立的，出生后减数分裂特异性凝聚素亚基没有得到补充，这增加了卵母细胞长时间减数分裂停滞促进凝聚力恶化的可能性，从而导致与年龄相关的非整倍性增加。我们在此通过免疫荧光分析卵巢切片检测了不同年龄组人类和小鼠的网状卵母细胞中的粘附素水平。减数分裂特异性粘附素亚基REC8和SMC1B在40岁及以上组较20岁左右组明显降低（P<0.01）。在小鼠中，减数分裂粘连蛋白的减少也是明显的。有趣的是，SMC1A，SMC1B的有丝分裂对应物，在人类卵母细胞中基本上是可检测的，但在小鼠中几乎没有表达。此外，小鼠的有丝分裂粘附素的量随着年龄的增长而略有增加。这些结果表明，有丝分裂和减数分裂凝聚素可能以协调的方式运作，以维持凝聚力在一个持续的时期在人类和年龄相关的减数分裂凝聚素亚基的减少损害姐妹染色单体凝聚力，导致分离错误增加。
Aneuploidy in fetal chromosomes is one of the causes of pregnancy loss and of congenital birth defects. It is known that the frequency of oocyte aneuploidy increases with the human maternal age. Recent data have highlighted the contribution of cohesin complexes in the correct segregation of meiotic chromosomes. In mammalian oocytes, cohesion is established during the fetal stages and meiosis-specific cohesin subunits are not replenished after birth, raising the possibility that the long meiotic arrest of oocytes facilitates a deterioration of cohesion that leads to age-related increases in aneuploidy. We here examined the cohesin levels in dictyate oocytes from different age groups of humans and mice by immunofluorescence analyses of ovarian sections. The meiosis-specific cohesin subunits, REC8 and SMC1B, were found to be decreased in women aged 40 and over compared with those aged around 20 years (P<0.01). Age-related decreases in meiotic cohesins were also evident in mice. Interestingly, SMC1A, the mitotic counterpart of SMC1B, was substantially detectable in human oocytes, but little expressed in mice. Further, the amount of mitotic cohesins of mice slightly increased with age. These results suggest that, mitotic and meiotic cohesins may operate in a coordinated way to maintain cohesions over a sustained period in humans and that age-related decreases in meiotic cohesin subunits impair sister chromatid cohesion leading to increased segregation errors.
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