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The effects of aging and apoptosis on oocyte quality in Caenorhabditis elegans females

by
Sara J. Andux
B.S., 1998
Cook College, Rutgers University
M.N.M., 2004
Regis University

Thesis Advisor: Ronald Ellis, Ph.D.
Cell and Molecular Biology Program

Science Center, Room 290

Tuesday, December 2, 2008
9 am


Abstract

In all women, fertility declines with age. This decline is due a decrease in both the quantity and the quality of their oocytes, which ultimately results in fewer pregnancies and an increased incidence of birth defects. We are using the nematode C. elegans to study how oocyte quality changes during aging, and to learn if it might be improved in older females. To assay quality, we determine the fraction of viable eggs after fertilization. Our results show that oocyte quality declines in aging nematodes, as in humans. Under normal conditions, physiological germ cell death maintains oocyte quality at all ages, and most of these deaths appear to promote the proper allocation of resources among developing oocytes. Following high levels of irradiation, the deaths of oocytes with damaged DNA also helps maintain oocyte quality in young females. Surprisingly, some of the genes that regulate DNA-damage-induced apoptosis are harmful to the oocytes of older mothers. Finally, the DAF-2/IGF signaling pathway is also harmful to oocytes in older females. Thus, mutations in these two pathways improve oocyte quality in older animals. We conclude that these pathways have been optimized for reproductive success early in life, but cause harm to later reproduction.


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