Factors influencing mammalian kidney development: implications for health in adult life

Abstract

There are many reasons why it is timely to review the development of the mammalian kidney. Perhaps the most important of these is the increasing amount of evidence to demonstrate that factors which impinge on/alter the normal developmental processes of this organ can have lifelong consequences for the health of the adult. The'Developmental Origins of Health and Adult Disease' (DOHaD) hypothesis, proposes that changes in the environment during the development of an organ or system, can have permanent deleterious effects leading to increased risk of cardiovascular and/or metabolic disease. The permanent metanephric kidney has been shown to be very vulnerable to such influences with many factors shown to alter both the permanent structure and the level of expression of important functional genes. Thus it is important to understand the precise timing of kidney development in terms of both structure and the genes involved at each stage. Such knowledge has been gained by significant advances in technology, which allow quantification of the number of nephrons by unbiased stereology, detections of both levels and site of gene expression,'knock-out' and knock-in' of genes in animal (mainly mouse) models and by the ability to examine nephron development, in real time, in culture systems.