The developmental origins of health and disease: current theories and epigenetic mechanisms

Abstract

The retrospective cohort studies of David Barker and colleagues during the late 1980s established the principle that the incidence of certain adult diseases such as stroke, type 2 diabetes and dyslipidaemia may be linked to in utero development. Later termed the "Developmental Origins of Health and Disease (DOHaD)" hypothesis, there have been several more recent attempts to explain this phenomenon. Although a general conceptual framework has been established to explain how mechanisms may have evolved to facilitate rapid adaptations to changing ecological conditions, it doesn't identify the actual mechanisms responsible for such effects. Extensive covalent modifications to DNA and related proteins occur from the earliest stages of mammalian development. These determine lineage-specific patterns of gene expression and so represent the most plausible mechanisms by which environmental factors can influence development during the life course. In providing a contemporary overview of chromatin modifications during early mammalian development, this review highlights both the complexity and our current lack of understanding of how epigenetic alterations may contribute to in utero programming. It concludes by providing some thoughts to future research endeavours where the emphasis should be on bettering our understanding of epigenesis and devising more thoughtful experimental approaches that focus on specific environmental factors in appropriate animal and cellular models.