Modelling the developmental origins of health and disease in the early embryo

The concept that certain adult diseases, such as hypertension, type 2 diabetes and dyslipidaemia can originate from events occurring in utero arose from epidemiological studies in humans but has since been supported by numerous animal-based studies. Referred to as the “developmental origins of health and disease” or “DOHaD” hypothesis, nutritional studies to date have largely focused on two experimental paradigms involving either calorie or protein restriction for varying intervals during pregnancy, where the favoured animal models have been the sheep and rat. In recent times, attention has been directed towards the earliest stages of gestation, where there is emerging evidence to indicate that the pre-implantation embryo may be particularly sensitive to environmentally induced perturbations leading to impaired health in adulthood. In this article, we make the case for hESCs as a model of the human pre-implantation embryo. Working with comparatively large populations of embryonic cells from the species of clinical interest, the scope exists to investigate the effects of specific genetic manipulations or combinations of metabolites against contrasting genetic backgrounds, where the consequences can be evaluated in downstream tissue specific progenitor and/or terminally differentiated cells. In order to fully realize these potentials, however, both derivation and culture conditions need to be harmonized and refined so as to preclude the requirement for feeder cells and serum.