GERM CELL GENOTOXICITY THE LASTING EFFECTS OF PEDIATRIC CANCER THERAPY

Abstract

In this thesis, I set out to examine fertility as a late effect of pediatric cancer therapy. I determine why fertility is an inadequate measure of the reproductive fitness of adult cancer survivors and explore the causes of deficits in fertility after pediatric cancer therapy. I focus mainly on the male germ cell line, exploring various sperm genomic damages that occur as a result of chemotherapy and/or radiotherapy in childhood and adolescence. Although sperm chromosome aneuploidy presents as a consequence of pediatric cancer therapy, I worry more with sperm DNA fragmentation, which includes single-strand and double-strand DNA breaks, which are genotoxic and have the ability to be transmitted to offspring. I find, however, that although DNA-impaired spermatozoa may fertilize an egg, it is unlikely for these damages to remain in the embryo or for the embryo to remain.