Introduction

Evidence both from epidemiological studies and from experimental animal models supports the concept of developmental programming (Osmond and Barker 2000, Sorensen et al. 2000, Barker 2002, Eriksson and Forsen 2002, Ozanne and Hales 2002). In studies of genetically homogeneous animals there are now unequivocal data demonstrating that environmental stress during the period from peri-implantation development through to the end of suckling can impact on the health status of the adult offspring, and can also have behavioural consequences (Langley-Evans and Jackson 1996, Ozanne et al. 1998, Khan et al. 2003, Vickers et al. 2003, Weaver et al. 2004). Amongst the disorders that have been reported after suboptimal maternal nutrition, the most common are hypertension, insulin resistance, dyslipidaemia, obesity and endothelial dysfunction. In one particularly well-characterised animal model adult offspring display all these symptoms, which in humans are collectively known as syndrome X (Khan et al. 2003, 2005). This constellation of disorders is predicted to be increasing at an alarming rate and is currently affecting large numbers of adults in the western world. A molecular understanding of developmental programming is not only a challenging academic problem, but also one that may enable us to devise preventative strategies, which will benefit human health and reduce medical care costs in the future.

Addressing the molecular mechanisms of developmental programming is difficult because the cellular disorders that lead to disease susceptibility in the adult occur long after the initial causative stress has been removed.