Grant: Project Grant

In recent decades, men in Canada have been fathering children at older ages. This development has been attributed to many factors including increased life expectancy, wide-spread use of contraception, changing socio-economic pressures, pursuit of higher education and careers, higher rates of divorce and remarriage, and increased access to Assisted Reproductive Technologies (ART). Epidemiological evidence indicates that advanced paternal age at conception is associated with higher risks of neurodevelopmental and neuropsychiatric disorders such as autism spectrum disorder and schizophrenia in the offspring. Alterations in the epigenetic marking of DNA, DNA methylation, has been implicated as one of the key underlying mechanisms of these paternal age-associated complex disorders in the next generation. In this grant proposal, we will conduct studies to further explore the link between age-related DNA methylation defects in fathers who either conceive children naturally or use ART and adverse perinatal and neurodevelopmental outcomes in their children. We expect to gain a fundamental understanding of how advanced paternal age can predispose some children to birth and developmental defects, with the hope of identifying biomarkers to detect which children will be at risk and approaches to prevention in the future.