Apoptosis Maintains Oocyte Quality in Aging Caenorhabditis elegans Females
Apoptosis Maintains Oocyte Quality in Aging Caenorhabditis elegans Females
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DOI：
10.1371/journal.pgen.1000295
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发表时间：
2008-12-01
期刊：
影响因子：
4.5
通讯作者：
Ellis, Ronald E.
中科院分区：
文献类型：
--
作者：
Andux, Sara;Ellis, Ronald E.
在女性中，卵母细胞在减数分裂I前期结束时停止发育，并保持静止多年。随着时间的推移，这些卵母细胞的质量和数量都会下降，导致怀孕的次数减少，出生缺陷的发生率增加。我们使用线虫秀丽线虫来研究卵母细胞质量是如何在老化过程中被调节的。为了检测质量，我们测定受精后产生可存活卵子的卵母细胞的比例。我们的结果表明，在老化的线虫中，卵母细胞的质量下降，就像人类一样。这种下降会影响到在早期晚期滞留的等待信号成熟的卵母细胞，也会影响在生命后期发育的卵母细胞。此外，阻止所有细胞死亡的突变会导致卵母细胞质量的严重早期下降，而且这种影响随着年龄的增长而增加。然而，仅阻止体细胞死亡或DNA损伤导致的死亡的突变不会降低卵母细胞的质量。有两条证据表明，大多数发育程序性生殖细胞死亡促进了资源在卵母细胞之间的适当分配，而不是消除了染色体受损的卵母细胞。首先，突变降低了卵母细胞的质量，这些突变不能阻止生殖细胞死亡，但会阻止细胞身体的吞噬和循环。其次，许多成熟卵母细胞的大小减少也反映了由凋亡突变所导致的质量下降。我们的结论是，对资源的竞争是老化生殖系中的一个严重问题，而细胞凋亡有助于缓解这个问题。
In women, oocytes arrest development at the end of prophase of meiosis I and remain quiescent for years. Over time, the quality and quantity of these oocytes decreases, resulting in fewer pregnancies and an increased occurrence of birth defects. We used the nematode Caenorhabditis elegans to study how oocyte quality is regulated during aging. To assay quality, we determine the fraction of oocytes that produce viable eggs after fertilization. Our results show that oocyte quality declines in aging nematodes, as in humans. This decline affects oocytes arrested in late prophase, waiting for a signal to mature, and also oocytes that develop later in life. Furthermore, mutations that block all cell deaths result in a severe, early decline in oocyte quality, and this effect increases with age. However, mutations that block only somatic cell deaths or DNA-damage-induced deaths do not lower oocyte quality. Two lines of evidence imply that most developmentally programmed germ cell deaths promote the proper allocation of resources among oocytes, rather than eliminate oocytes with damaged chromosomes. First, oocyte quality is lowered by mutations that do not prevent germ cell deaths but do block the engulfment and recycling of cell corpses. Second, the decrease in quality caused by apoptosis mutants is mirrored by a decrease in the size of many mature oocytes. We conclude that competition for resources is a serious problem in aging germ lines, and that apoptosis helps alleviate this problem.