An increasing number of studies indicate that drugs, diet and other environmental factors to which individual’s are exposed alter fetal origins of disease and health outcomes in their children, and even grandchildren. In many cases these effects are thought to be mediated by epigenetic changes in the germline that are transmitted by the sperm or egg to the offspring. Epigenetic modifications alter the way DNA is packaged in the cell and the selection of genes that can be switched on or off in each cell type. Significantly, epigenetic signatures are heritably transmitted from cell to cell, providing a memory of cellular identity and function. During development, epigenetic information is removed from the precursors of the egg and sperm, the developing germ cells. Specific enzymes then catalyse new epigenetic modifications in fetal germ cells, and in the maturing sperm and eggs in adults. Errors in these processes can lead to epigenetic changes in the sperm and egg that are transmitted to the offspring, but the epigenetic mechanisms involved and extent to which altered epigenetic state in germ cells impacts on development and health in offspring is very poorly understood.
Enzymes that catalyse epigenetic changes are commonly altered in cancer, and development of drugs that target epigenetic mechanisms has become an important focus in oncology. These drugs offer important new treatments for patients, but their impacts on the germline epigenome are almost completely unknown. As these drugs become more widely used in the clinic, it is increasingly likley that patients will want to conceive children. Since these drugs directly target epigenetic mechanisms it is of considerable importance that we understand their potential impacts on the germline epigenome, particularly during the maturation of male and female gametes. This talk will provide an example of a clinically relevant drug that can significantly alter germline epigenetic state, and will discuss the relevance of understanding the potential germline impacts of these drugs for patients intending to conceive children, post treatment.