Placental amino acid transport systems and fetal growth restriction – A workshop report

Abstract

Keywords: Placental amino acid transport; Fetal growth restriction; Amino acid transportersINTRODUCTIONTwo circulations perfuse the placental barrier, the maternal oruterine on one side and the fetal or umbilical on the other.This barrier consists of two specific membranes, the maternalfacing, microvillous (MVM) or apical membrane and the fetalfacing or basal membrane (BM). As human gestation advancesthe surface area of the microvillous membrane increases.Though late in pregnancy, this increase is not of comparablerate to the growth rate of the fetus, supporting the concept thatduring later pregnancy the increasing physiological needs ofthe fetus are achieved by multiple functional changes in thetotal placental exchange capacity. One component of thiscapacity is amino acid transport. Both placental membraneshave a range of active energy dependent amino acid transportsystems [1]. These systems act in a coordinated manner totransport amino acids from both circulations into thetrophoblast, as well as out of the trophoblast, into circulation.In addition to surface area, many other factors also influenceoverall activity. Maternal circulating concentrations of aminoacids also play a major role in regulating umbilical uptake,where the transport of any given amino acid from placenta tofetus is considered a function of both its own maternalconcentration and the maternal concentration of inhibitoryamino acids [2]. Additionally, electrical gradients exist over theplacenta, across which transport systems operate, indicative ofthe energy requirement of these systems [3]. It is important toremember that the trophoblast acts not only as a conduit foramino acids between the two circulations, but also has a highmetabolic rate, utilizing amino acids for its own metabolicfunctions, which include hormone and steroid production aswell as waste removal from fetal circulation [4].To understand the overall functional capacity of theplacental barrier, attempts to consider all of the abovecomponents need to be made, especially when investigatinghow adverse situations may impact upon the developmentaland functional capacity of the placenta. Specifically, in thesituation of fetal growth restriction (FGR), there is in vivo andin vitro data to demonstrate significant changes in the placentalsurface area/permeability constants [5], its amino acid trans-port activity in vitro [6e8], and in vivo [9e12]. The FGRplacenta has decreased total villous surface area, indicating thatmorphometric changes in vascularization may contribute to theoverall reduction in placental diffusional transport capacity.Thus, both decreased surface area for diffusional exchange forcompounds such as oxygen and reductions in the number ofspecific nutrient transporters and their activities may contrib-ute to a global reduction in nutrient transport in FGRpregnancies.The purpose of this workshop was to deal with a range ofwork representing aspects of amino acid transport systems,including their locations, their substrates and their activities,from both in vitro and in vivo settings. However, rather thanact as a forum for mini reviews, this workshop was designedfor presenters to put forward experimental inconsistencies insome of these aspects for general discussion and input from thegathered group. The aim, at the end of the workshop, was tohave a consensus of where specific placenta amino acidtransporters may be located, what their substrates and theirindividual activities may be, how they might interact with one