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Comments on Wei, Qing et al. (2011) International Worm Meeting "Regulation of oocyte quality by the level of germ cell death." (0)
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Wei, Qing, Andux, Sara, & Ellis, Ronald (2011). Regulation of oocyte quality by the level of germ cell death presented in International Worm Meeting. Unpublished information; cite only with author permission.
As women age, the quality and quantity of their oocytes declines, resulting in a lower chance of getting pregnant and a higher chance of birth defects. We are using C. elegans to study this problem. Previous work showed that oocyte quality decreased with age in C. elegans females, and that physiological germ cell deaths maintain oocyte quality, possibly by reducing the number of oocytes that compete for resources. Although blocking all germ cell deaths leads to poor oocyte quality, we don't know the relationship between the frequency of germ cell death and oocyte quality. Is it linear? Is the level of germ cell deaths in wildtype animals optimal during aging? To answer these questions, we are testing mutants with moderate effects on germ cell death. Mutations that increase the number of deaths include those in the transcription factor pax-2, which regulates the expression of ced-9; and in csp-2, which inhibits ced-3 autoactivation. Mutations that decrease the number of germ cell deaths include weak alleles of ced-3. We found that pax-2 mutants and csp-2 mutants produce slightly worse oocytes than the wild type. Moreover, ced-3 weak alleles also produce oocytes of poorer quality of than the wild type, but not as poor as those of strong ced-3 mutants. Because either increasing or decreasing the number of germ cells can lower oocyte quality, the relationship between the level of germ cell deaths and oocyte quality is not linear. Surprisingly, our studies of the DNA-damage-induced cell death pathway show that in some conditions, mutations in egl-1 and ced-13 improve oocyte quality in old animals. Since these egl-1; ced-13 mutants have fewer germ cell deaths than the wild type, the number of germ cell death might not be optimal in older wildtype animals. We also found that mutants that disrupt the Insulin/IGF signaling pathway improve oocyte quality in older females. However; this effect appears to be independent of apoptosis.
Affiliation:
- Molec Biol, UMDNJ-SOM, GSBS, Stratford, NJ.