Intergenerational Transmission of Paternal Epigenetic Marks: Mechanisms Influencing Susceptibility to Post-Concussion Symptomology in a Rodent Model

Abstract

Abstract Epigenetic transmission of phenotypic variance has been linked to paternal experiences prior to conception and during perinatal development. Previous reports indicate that paternal experiences increase phenotypic heterogeneity and may contribute to offspring susceptibility to post-concussive symptomology. This study sought to determine if epigenetic tags, specifically DNA methylation of promoter regions, are transmitted from rodent fathers to their sons. Using MethyLight, promoter methylation of specific genes involved in recovery from concussion and brain plasticity were analyzed in sperm and brain tissue. Promoter methylation in sperm differed based on paternal experience. Differences in methylation were often identified in both the sperm and brain tissue obtained from their sons, demonstrating transmission of epigenetic tags. For certain genes, methylation in the sperm was altered following a concussion suggesting that a history of brain injury may influence paternal transmission of traits. As telomere length is paternally inherited and linked to neurological health, this study examined paternally derived differences in telomere length, in both sperm and brain. Telomere length was consistent between fathers and their sons, and between brain and sperm, with the exception of the older fathers. Older fathers exhibited increased sperm telomere length, which was not evident in sperm or brain of their sons.