Utility of preclinical models of altered maternal nutrition to support the developmental origins of health and disease hypothesis.

Abstract

A clear link has been established between alterations in the early life environment and the risk for developing a range of cardiometabolic diseases in later life, a process preferentially termed developmental programming. In particular, alterations in the maternal nutritional environment have been associated with a range of adverse health outcomes in offspring across the lifecourse; effects that can be passed on to future generations. Following from the early epidemiological observations that provided the basis for the developmental origins of health and disease (DOHaD) hypothesis, a range of animal models were developed to examine the impact of early life programming and provide empirical data to support the emerging framework. These models became key tools to aid in our understanding of developmental programming as allowed investigation of potential mechanisms, strategies for intervention and transgenerational effects. The study published by Langley and Evans (Clin. Sci. 1994;86(2):217–222; DOI:10.1042/CS0860217), using a rat model of maternal low protein exposure, was one of the first to highlight the impact of an altered maternal nutritional environment on programming of elevated blood pressure in offspring. This work became a hallmark study in the DOHaD field by demonstrating key proof of principle to support the early epidemiological associations and characterizing a key preclinical model that has contributed greatly to our understanding of mechanisms underpinning developmental programming—particularly in the area of cardiovascular and renal function.