Transgenerational Epigenetic Inheritance: Does It Exist?

Abstract

Introduction: Epigenetic inheritance refers to the mechanisms for transmission of gene regulatory information which is not coded in the DNA sequence (i.e. not genetic) through successive cellular divisions (mitosis and/or meiosis). It plays a crucial role for the development and importantly, through epigenetic changes, environmental influences (food, smoking, etc.) can be `remembered` and could have long lasting effects after exposure. Transgenerational epigenetic inheritance (TEI) refers to the transmittance of epigenetic information between successive generations and it is generally accepted that such a process (with a few exceptions) does not occur as there is extensive epigenetic reprogramming and every new generation starts with an epigenetically `clean slate`. Currently, there are convincing demonstrations of transgenerational inheritance of an epigenetic state at a few loci in plants and mice and the evidence in humans is mainly indirect. Nonetheless, even if the epigenetic state of a small number of genes in humans is transgenerationally inherited, it would herald a major shift in the way we think about the inheritance of phenotype. With this in mind, our aim is to review current literature to assess the evidence for existence of TEI in humans and to review its possible mechanisms. Materials and Methods: We performed a PubMed search and analysis of articles containing the term `transgenerational epigenetic inheritance` in their title. Results: At the time of writing there were 31 articles indexed in PubMed corresponding to the given search criteria, nine of which concern TEI in humans. A major drawback in the field is the lack of a clear definition of transgenerational epigenetic inheritance and clear discrimination from inherited epimutation. There are no articles presenting solid evidence for the TEI phenomenon in humans. Possible key mechanisms of transmission are DNA methylation, histone modifications, and non-coding RNAs. Conclusions: There is still lack of solid evidence for the phenomenon of transgenerational epigenetic inheritance in humans.