Obesity and nutritional programming of the paternal sperm epigenome: effects on offspring development and health

The impact of diet and body condition on the father's reproductive health and that of his offspring has been relatively under-explored and under-emphasized. Over the past two decades male fertility is declining as measured by lowered sperm counts, increased DNA damage in sperm and rising rates of testicular cancer. Other factors contributing to increasing male infertility are the increase in chronic diseases that are widespread including, obesity, cardiovascular disease and metabolic disorders. While we know each of these factors can negatively impact sperm counts and quality, what is even more alarming is the emerging evidence from the field of epigenetics which suggests these factors are not limited to just damaging male fertility, but may passed on to influence the health of children and perhaps even grandchildren. So how does sperm transmit information concerning diet and body condition across generations? It involves a biochemical set of information that is hereditary just like DNA, but sits on top, or within the DNA and controls whether a gene is turned active or not. The overall research question we address is: Does a father's diet and body mass index predispose his offspring to chronic disease or developmental defects and how is this information related to the sperm epigenome? The mechanisms underlying transmission of environmental memory from parents to offspring is far from understood. In prior studies we demonstrated that a folate deficient diet altered the sperm epigenome and that these changes were associated to genes implicated in development and chronic disease. In humans fast food diets, obesity and its metabolic sequelae are known to alter folate metabolism. Using data from murine models and human samples collected from a fertility clinic we will determine how folate and body mass affects the sperm epigenome, its association with markers of chronic disease and the consequences for offspring.