Grant: Operating Grant

The exposure of males to many chemicals may affect their germ cells and result in embryo death, malformations, and behavioural abnormalities in their progeny. We are studying the effects of two treatment paradigms, a single drug,cyclophosphamide, and the drug regimen used to treat men with testicular cancer, bleomycin, etoposide and cis-platin. We have shown that the adverse effects on progeny resulting from paternal exposures to these drugs are associated with altered gene expression in sperm at key stages of sperm production. Our goal is to find out the mechanisms by which paternal exposures affect the structure and organization of the male genome and how these effects may impact on the embryo. These studies will establish a mechanistic understanding of how paternal chemical exposures alter male germ cell quality with the long term goal of preventing adverse effects on subsequent generations. These studies are relevant clinically since an increasing number of young men survive their cancer treatments and seek to be fathers.