Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and embryo death in mice
Inadequate histone deacetylation during oocyte meiosis causes aneuploidy and embryo death in mice
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DOI：
10.1073/pnas.0510946103
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发表时间：
2006-05-09
影响因子：
11.1
通讯作者：
Aoki, Fugaku
中科院分区：
文献类型：
--
作者：
Akiyama, Tomohiko;Nagata, Masao;Aoki, Fugaku
减数分裂染色体分离错误是自然流产和出生缺陷的主要原因。几乎所有这样的非整倍性都源于女性的减数分裂错误，母亲年龄的增加是一个主要的危险因素。最近有报道称，哺乳动物卵母细胞在减数分裂期间整体去乙酰化，而非有丝分裂。在本研究中，发现抑制减数分裂组蛋白去乙酰化可诱导受精卵母细胞非整倍体，从而导致胚胎发育早期在子宫内死亡。此外，在年龄较大（10个月）的雌性小鼠的卵母细胞中，一种组蛋白仍然乙酰化，这表明在这类小鼠的卵母细胞中，组蛋白去乙酰化的功能降低了。因此，组蛋白去乙酰化可能参与了减数分裂过程中染色体的公平分布。老年女性胚胎非整倍体的高发生率可能是由于减数分裂组蛋白去乙酰化不足。
Errors in meiotic chromosome segregation are the leading cause of spontaneous abortions and birth defects. Almost all such aneuploidy derives from meiotic errors in females, with increasing maternal age representing a major risk factor. It was recently reported that histories are globally deacetylated in mammalian oocytes during meiosis but not mitosis. In the present study, inhibition of meiotic histone deacetylation was found to induce aneuploidy in fertilized mouse oocytes, which resulted in embryonic death in utero at an early stage of development. In addition, a histone remained acetylated in the oocytes of older (10-month-old) female mice, suggesting that the function for histone deacetylation is decreased in the oocytes of such mice. Thus, histone deacetylation may be involved in the fair distribution of chromosomes during meiotic division. The high incidence of aneuploidy in the embryos of older females may be due to inadequate meiotic histone deacetylation.