Somatic cell nuclear reprogramming of mouse oocytes endures beyond reproductive decline
Somatic cell nuclear reprogramming of mouse oocytes endures beyond reproductive decline
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DOI：
10.1111/j.1474-9726.2010.00644.x
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发表时间：
2011-02-01
期刊：
影响因子：
7.8
通讯作者：
Boiani, Michele
中科院分区：
文献类型：
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作者：
Esteves, Telma Cristina;Balbach, Sebastian Thomas;Boiani, Michele
哺乳动物卵母细胞具有支持受精和正常发育的独特功能，同时能够将体细胞核重编程为多能性，有时甚至是全能性。虽然已知卵母细胞质量随着体细胞老化而衰退，但不同的生物功能同时衰退并不是一个给定的事实。在这项研究中，我们测试了卵母细胞的重编程能力是否随着年龄的增长而下降。我们发现，从年龄超过通常的生殖年龄（更年期）的小鼠中分离的卵母细胞产生的卵母细胞在体细胞核移植（SCNT）后保留重编程能力，与年轻供体卵母细胞相比，产生更高的囊胚率。尽管更年期和年轻的卵子之间的转录组的差异，SCNT囊胚的基因表达谱是非常相似的。重要的是，具有从所有胚层分化成组织的能力的胚胎干细胞系源自从更年期卵子获得的SCNT囊胚。虽然更年期卵质体中凋亡相关基因下调，转录因子重编程（直接诱导多能性）受益于抑制p53介导的凋亡，年轻卵质体的重编程能力并没有提高阻断p53。然而，更多的副产物来自于在p53抑制剂存在下发育的SCNT囊胚，表明对滋养外胚层功能的有益作用。结果强烈表明，卵母细胞诱导的重编程结果是由内在的亲和抗重编程因子的可用性和平衡决定的，这些因子在整个衰老过程中受到严格的调节，甚至得到改善，从而提出了卵母细胞仍然可以成为体细胞重编程的资源，当它们不再被认为是安全的有性生殖时。
P>The mammalian oocyte has the unique feature of supporting fertilization and normal development, while capable of reprogramming nuclei of somatic cells toward pluripotency, and occasionally even totipotency. While oocyte quality is known to decay with somatic aging, it is not a given that different biological functions decay concurrently. In this study, we tested whether oocyte's reprogramming ability decreases with aging. We show that oocytes isolated from mice aged beyond the usual reproductive age (climacteric) yield ooplasts that retain reprogramming capacity after somatic nuclear transfer (SCNT), giving rise to higher blastocysts rates compared to young donors ooplasts. Despite the differences in transcriptome between climacteric and young ooplasts, gene expression profiles of SCNT blastocysts were very similar. Importantly, embryonic stem cell lines with capacity to differentiate into tissues from all germ layers were derived from SCNT blastocysts obtained from climacteric ooplasts. Although apoptosis-related genes were down-regulated in climacteric ooplasts, and reprogramming by transcription factors (direct-induced pluripotency) benefits from the inhibition of p53-mediated apoptosis, reprogramming capacity of young ooplasts was not improved by blocking p53. However, more outgrowths were derived from SCNT blastocysts developed in the presence of a p53 inhibitor, indicating a beneficial effect on trophectoderm function. Results strongly suggest that oocyte-induced reprogramming outcome is determined by the availability and balance of intrinsic pro- and anti-reprogramming factors tightly regulated and even improved throughout aging, leading to the proposal that oocytes can still be a resource for somatic reprogramming when they cease to be considered safe for sexual reproduction.