Review: The placenta and developmental programming: balancing fetal nutrient demands with maternal resource allocation.

The placenta evolved to support development of the fetus, and so potentially plays a key role in the aetiology of developmental programming through its impact on nutrient transfer. Placental transport efficiency depends on a variety of parameters, including surface area for exchange, thickness of the interhaemal membrane and density of transporter proteins inserted into the trophoblast membranes. Here, we review recent studies that tested whether adaptations of placental efficiency are induced in the mouse placenta when maternal nutrient supply and fetal demand are manipulated experimentally. Naturally small placentas, and those exposed to maternal undernutrition, displayed structural changes indicative of accelerated maturation at E16, with enlargement of the labyrinth exchange zone at the expense of the endocrine junctional zone. These changes were associated with increased transport of a non-metabolisable amino acid analogue per gram of placenta, and expression of genes encoding specific System A transporters. Up-regulation of transporters was also observed when a mismatch between placental size and fetal demand was generated through genetic manipulation of the Igf2/H19 axis. Conversely, overgrowth of the placenta induced by deletion of H19 resulted in reduced transport capacity and expression of transporter genes. We conclude that under conditions when the maternal nutrient supply or placental size may be limiting for normal fetal growth, the placenta adapts so as to increase its transport capacity. Hence, it ameliorates the effects of environmental cues that would otherwise lead to more extensive developmental programming. The P0 transcript of Igf2 appears to be a strong candidate as a mediator of these adaptations in the mouse.