Abstract
Amino acid transfer to the fetus is dependent on several different factors. While these factors can be understood in isolation, it is still not possible to predict the function of the system as a whole. In order to do this an integrated approach is required which incorporates the interactions between the different determinants of amino acid transfer. Computational modelling of amino acid transfer in the term human placenta provides a mechanism by which this integrated approach can be delivered. Such a model would be invaluable for understanding amino acid transfer in both normal and pathological pregnancies.In order to develop a computational model it is necessary to determine all the biological factors which are important contributors to net amino acid transfer and the ways in which they interact. For instance, how different classes of amino acid transporter must interact to transfer amino acids across the placenta. Mathematically, the kinetics of each type of transporter can be represented by separate equations that describe their transfer rate as a non-linear function of amino acid concentrations. These equations can then be combined in the model to predict the overall system behaviour. Testing these predictions experimentally will demonstrate the strengths and weaknesses of the model, which can then be refined with increasing complexity and retested in an iterative fashion.In this way we hope to develop a functional computational model which will allow exploration of the factors that determine amino acid transfer across the placenta. This model may also allow the development of strategies to optimise placental transfer in pathologies associated with impaired amino acid transfer such as fetal growth restriction.
Highlights
Placental amino acid transfer is essential for fetal growth
The complex interactions between these factors mean that the effect of all these determinants together cannot be intuitively predicted [3]. This limits our ability to understand how these factors contribute to net flux across the placenta and which of these factors are most likely to be ratelimiting for amino acid transfer and so for fetal growth
We have previously reported on modelling the interaction of specific transporters with two amino acids [4]
Summary
Placental amino acid transfer is essential for fetal growth. In growth restricted fetuses amino acid transfer across the placenta is reduced and in animal models amino acid transfer has been shown to be decreased prior to the onset of fetal growth restriction, emphasising its causal role [1,2]. It is important to understand the factors which determine amino acid transfer across the placenta if we are to develop interventions and preventive strategies to optimise fetal growth. The complex interactions between these factors mean that the effect of all these determinants together cannot be intuitively predicted [3] This limits our ability to understand how these factors contribute to net flux across the placenta and which of these factors are most likely to be ratelimiting for amino acid transfer and so for fetal growth. This review will begin by outlining our approach to developing a computational model It will consider the processes by which amino acids are transported across the placenta in order to identify those factors which are likely to be important components of a computational model. Lewis et al / Placenta 34, Supplement A, Trophoblast Research, Vol 27 (2013) S46eS51
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