Embryos, DOHaD and David Barker.

The early embryo and periconceptional period is a window during which environmental factors may cause permanent change in the pattern and characteristics of development leading to risk of adult onset disease. This has now been demonstrated across small and large animal models and also in the human. Most evidence of periconceptional 'programming' has emerged from maternal nutritional models but also other in vivo and in vitro conditions including assisted reproductive treatments, show consistent outcomes. This short review first reports on the range of environmental in vivo and in vitro periconceptional models and resulting long-term outcomes. Second, it uses the rodent maternal low protein diet model restricted to the preimplantation period and considers the stepwise maternal-embryonic dialogue that comprises the induction of programming. This dialogue leads to cellular and epigenetic responses by the embryo, mainly identified in the extra-embryonic cell lineages, and underpins an apparently permanent change in the growth trajectory during pregnancy and associates with increased cardiometabolic and behavioural disease in adulthood. We recognize the important advice of David Barker some years ago to investigate the sensitivity of the early embryo to developmental programming, an insight for which we are grateful.