304 - The Paternal Programming of Periconception Development

Abstract: There is now a significant body of human and animal model data which identify common associations between perturbed development during gestation, disproportionate fetal growth and poor adult cardiovascular and metabolic health. Typically, these studies focus on the impact of poor maternal health on offspring development and well-being. However, a growing evidence base now indicates that sub-optimal paternal factors (such as diet) can also program adult offspring ill-health. While the link between paternal health and offspring well-being is becoming established, attention is being focused on defining the underlying mechanism(s). Here, the father may influence post-fertilization development through two main pathways, the integrity and status of the sperm genome (including epigenome) and through components of the seminal plasma. We have used mouse models of poor-quality diet to study the impact sub-optimal paternal nutrition has on the quality and epigenetic status of the sperm, embryonic development and fetal growth. We have also used our models to study the relative seminal plasma and sperm contributions to adult offspring cardiovascular and metabolic health. Our studies identify a continuum of changes ranging from testicular morphology, sperm epigenetic status, preimplantation embryo development, fetal growth and adult offspring cardio-metabolic ill-health in response to either over or undernutrition. Interestingly, we also observed that these long-term offspring effects appear mediated through specific sperm and seminal plasma specific mechanisms. Our data highlight the significance of a father’s diet at the time of conception for the development and well-being of his offspring.