Environmental epigenetic inheritance through gametes and implications for human reproduction.

BACKGROUND Traditional studies focused on DNA as the heritable information carrier that passes the phenotype from parents to offspring. However, increasing evidence suggests that information, that is independent of the DNA sequence, termed epigenetic information, can be inherited between generations. Recently, in our lab, we found that prediabetes in fathers increases the susceptibility to diabetes in offspring through gametic cytosine methylation changes. Paternal prediabetes changed overall methylation patterns in sperm, and a large portion of differentially methylated loci can be transmitted to pancreatic islets of offspring up to the second generation. In this review, we survey the extensive examples of environmentally induced epigenetic inheritance in various species, ranging from Caenorhabditis elegans to humans. We focus mainly on elucidating the molecular basis of environmental epigenetic inheritance through gametes, which is an emerging theme and has important implications for explaining the prevalence of obesity, type 2 diabetes and other chronic non-genetic diseases, which is also important for understanding the influence of environmental exposures on reproductive and overall health in offspring. METHODS For this review, we included relevant data and information obtained through a PubMed database search for all English language articles published up to August 2014 which included the term ‘environmental epigenetic inheritance’ and ‘transgenerational epigenetic inheritance’. We focused on research papers using animal models including Drosophila, C. elegans, mouse and rat. Human data were also included. RESULTS Evidence from animal models suggests that environmental epigenetic inheritance through gametes exists in various species. Extensive molecular evidence suggests that epigenetic information carriers including DNA methylation, non-coding RNAs and chromatin proteins in gametes play important roles in the transmission of phenotypes from parents to offspring. CONCLUSIONS Given the large number of experimental evidence from various organisms, it is clear that parental environmental alterations can affect the phenotypes of offspring through gametic epigenetic alterations. This more recent thinking based on new data may have implications in explaining the prevalence of obesity, type 2 diabetes and other chronic non-genetic diseases. This also implies that, in the near future, epigenetic factors which are heritable should be regarded important in determining the risk of certain diseases. Moreover, identification of epigenetic markers in gametes (polar body or sperm) may hold great promise for predicting susceptibility to and preventing certain non-genetic diseases in offspring, as well as providing indications on parental environmental exposures. [ABSTRACT FROM PUBLISHER]