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Apoptosis maintains oocyte quality in aging Caenorhabditis elegans females.
PLoS Genet. 2008 Dec; 4(12):e1000295
Helen Chamberlin, Ohio State University, OH, USA. F1000 Developmental Biology
08 Jan 2009 | New Finding
I like this paper because it provides a new way to think about the role of cell death in oocyte production and how this could lead to more viable eggs.
As with other animals, apoptosis of germ cells occurs in the C. elegans female germline, and the proportion of dying cells increases with age {1}. Previously, the biological role of this cell death was not entirely clear, especially since mutants defective in apoptosis were fertile. Through careful manipulation and measurement of maternal age and embryonic survival, the authors show that, in C. elegans, embryonic viability decreases with maternal age, and that this effect is exacerbated in mothers defective in germline apoptosis. The results argue that the role of cell death during oocyte production is to maintain the quality of the surviving oocytes, through the freeing-up of cellular resources, or other mechanisms. An exciting future direction will be to investigate the interaction between the maintenance of oocyte quality and pathways known to regulate aging.
Reference: {1} Gumienny et al. Development 1999, 126:1011-1022 [PMID:9927601].
Competing interests: None declared
Chamberlin H: "I like this paper because it provides a new way to think about the role..." Evaluation of: [Andux S, Ellis RE. Apoptosis maintains oocyte quality in aging Caenorhabditis elegans females. PLoS Genet. 2008 Dec; 4(12):e1000295; doi: 10.1371/journal.pgen.1000295]. Faculty of 1000, 08 Jan 2009. F1000.com/1136876#eval593970
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Chamberlin H: 2009. F1000.com/1136876#eval593970
Morris F Maduro, University of California Riverside, CA, USA. F1000 Developmental Biology
03 Feb 2009 | New Finding
The authors show that in C. elegans, as in humans, oocytes decline in quality with maternal age. Blocking of germline apoptosis by ced-3 or ced-4 mutation causes even further decline, but unexpectedly this is not simply due to elimination of DNA-damaged oocytes.
Instead, apoptosis seems to regulate how maternal resources are allocated to oocytes. Production of lower-quality oocytes is strongly correlated with decreased oocyte size, further suggesting that these resources are likely to be limited. The authors have established a nice system that couples the detailed knowledge of C. elegans biology with a rich suite of genetic tools. Now that this system is established, new questions are raised. If oocyte deaths allow redistribution of resources to oocytes, what are the resources that are in limited supply? Are they proteins, mRNAs or other molecules? There are known maternal-effect lethal mutations that can produce a decrease in oocyte/embryo size, such as ooc-3 or ooc-5 {1}, suggesting that it may be possible to identify such genes. Finally, a broader question is raised of how the abundance or quality of these resources related to the environment of the mothers in the wild.
Reference: {1} Basham and Rose, Dev Biol 1999, 215:253-63 [PMID:10545235].
Competing interests: None declared
Maduro M F: "The authors show that in C. elegans, as in humans, oocytes decline in quality with..." Evaluation of: [Andux S, Ellis RE. Apoptosis maintains oocyte quality in aging Caenorhabditis elegans females. PLoS Genet. 2008 Dec; 4(12):e1000295; doi: 10.1371/journal.pgen.1000295]. Faculty of 1000, 03 Feb 2009. F1000.com/1136876#eval604476
Short form
Maduro M F: 2009. F1000.com/1136876#eval604476
Faculty of 1000 evaluations, dissents and comments for [Andux S, Ellis RE. Apoptosis maintains oocyte quality in aging Caenorhabditis elegans females. PLoS Genet. 2008 Dec; 4(12):e1000295; doi: 10.1371/journal.pgen.1000295]. Faculty of 1000, 03 Feb 2009. F1000.com/1136876
Short form
Faculty of 1000: 2009. F1000.com/1136876
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.
DOI: 10.1371/journal.pgen.1000295
PMID: 19057674
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