Host: The Japanese Society of Toxicology
In recent years, the Developmental Origin of Health and Disease (DOHaD) theory, which claims that the causes of offspring’s health and disease can be traced back to the fetal period, has been gaining attention. DOHaD classically focuses on the uterine environment for the fetus, such as maternal nutritional intake and drug exposure. However, recent epidemiological studies have pointed out that paternal factors may also influence the next generation (Paternal Origin of Health and Disease, POHaD). For example, it has been repeatedly reported that there is an increase in low birth weight and neurodevelopmental disorders in children born to older fathers. In the United States, a longitudinal study (EARLI study) was conducted in an attempt to identify risk factors for autism spectrum disorder (ASD), a neurodevelopmental disorder (http://www.earlistudy.org/). The results of this study showed that paternal sperm DNA methylation changes were indeed correlated with ASD-like signs in the offspring, and that several of these DNA methylation changes were also common in autopsied brains of ASD patients. Based on this background, we have been studying the molecular mechanisms by which paternal aging is associated with the risk of neurodevelopmental disorders in children using aged male mice, and have focused on transgenic epigenomic mutations. In addition to paternal aging, it is becoming clear that the male germline epigenome, which can be altered by various factors such as endocrine disruptors, is a risk factor for disease in children. This also implies that offspring can have diverse phenotypes as a result of transgenerational effects of sperm-mediated epigenomics. The perspective of transgenerational effects of epigenomic variation may provide new insights into this issue.
