Abstract
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.
Highlights
As women age, the quality and quantity of their oocytes decline, resulting in a decreased chance of becoming pregnant and an increased chance of having a child with birth defects [1,2]
We show that oocyte quality declines in these small animals during aging, much as in mammals
Since many oocytes die in humans as well as in nematodes, our studies point to the possibility of improving oocyte quality by manipulating cell death in the germ line
Summary
The quality and quantity of their oocytes decline, resulting in a decreased chance of becoming pregnant and an increased chance of having a child with birth defects [1,2]. A major cause of this decline is the increasing fraction of oocytes with chromosomal abnormalities, such as those that cause Down’s syndrome These abnormalities are caused, at least in part, by defects in recombination and chromosome cohesion during meiosis [3,4]. The accumulation of other types of mutations, a decreased ability to eliminate defective oocytes, or fewer resources to nurture developing oocytes might contribute to the decline in oocyte quality. While this decline in quality is occurring, many other oocytes are undergoing apoptosis [5]. It is not known what role these apoptotic deaths play in oogenesis and the maintenance of oocyte quality
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