Grant: Team Grant: Boys' and Men's Health - General

Over the past 20 years, there is a clear trend for men to start having children at an increasingly older age. It is well-recognized that there is an association between maternal age and decreased fertility, higher incidence of abnormalities and diseases in their children; however, we are only beginning to grasp the impact of paternal age on fertility and progeny outcome. The objective of this Team Grant application is to examine how the trajectory of aging presents health challenges faced not only for older men but also for their children. Men older than 40 years of age take a longer time to make their partner pregnant and have a higher rate of infertility; partners of these men have a higher incidence of miscarriage. Paternal age is also linked to a higher risk for progeny to develop complex multi-gene diseases, such as autism, schizophrenia, and bipolar disease. Since sperm continue to be produced in men constantly throughout adult life at a rate of about 1000 sperm every heartbeat, decreased sperm cell function is likely to be associated with decreased sperm quality and not number. The central hypothesis underlying this Team Grant is that the trajectory of aging alters the quality of the sperm being delivered to the oocyte and that there is a direct relationship between infertility, paternal age, chromatin quality, epigenetic marks, and progeny outcome. The proposed studies represent a unique approach. There has been little attention to the quality of men's sperm as men move along their aging trajectory. The consequences of increased paternal age are only beginning to be demonstrated in studies from other countries. Our team has gathered the essential complementary expertise to make significant advances in this field. Our results will not only have positive consequences for men as they appreciate the link between aging and sperm chromatin quality but will also serve to decrease the health burden on future generations.