Proceedings of The Physiological Society

Future Physiology (Leeds, UK) (2017) Proc Physiol Soc 39, PC37

Poster Communications

Placental cell accumulation of substrates transported by system A is inversely related to placental size

K. McIntyre1, S. Greenwood1, C. Hayward1, C. Sibley1, M. Dilworth1

1. Maternal and Fetal Health Research Centre, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.

During pregnancy, nutrients required by the developing fetus must be transferred via the placenta. Thus, placental nutrient transport is a key determinant of fetal growth and size at birth. Activity of the placental system A amino acid transporter is reduced in fetal growth restriction (FGR, affects 5-10% of UK pregnancies), indicating its importance for appropriate fetal growth. In mice and humans, system A activity (per mg membrane protein) in normal pregnancy (measured using the non-metabolisable substrate methylaminoisobutyric acid, MeAIB) is inversely related to placental size, suggesting an adaptation that facilitates appropriate fetal growth. Glutamine, transported by systems A, L and N, and glutamate (XAG-) are important amino acids (AA) for fetal growth. We tested the hypothesis that placental accumulation of MeAIB, glutamine and glutamate, per mg protein, is inversely correlated to placental weight. Placental villous fragments from 11 uncomplicated pregnancies were maintained in medium with AA concentrations equivalent to maternal plasma and trace amounts of 14C-MeAIB, 14C-glutamine or 14C-glutamate. Radiolabel accumulation, expressed as pM/mg fragment protein, was assessed over 1-26hr (37°C). Accumulation at steady state was taken to reflect AA concentration in the tissue at equilibrium. For each radiolabelled AA, accumulation reached steady-state at 24 hr. Accumulation was inhibited by ouabain (Na+K+-ATPase inhibitor 1mM; 79-92%) and unlabelled substrates (10mM;80-90%;n=3) indicating that AA accumulation was predominantly intracellular and achieved by membrane transport. Birthweight and placental weight were positively correlated (p<0.004). 14C-MeAIB and 14C-glutamine accumulation (pmol/mg) were negatively correlated with placental weight (p<0.05; p=0.06) and birthweight (p<0.05; p<0.003, linear regression). Accumulation of 14C-MeAIB and 14C-glutamine was significantly correlated (p<0.001). In contrast, 14C-glutamate accumulation was unrelated to birthweight, placental weight or accumulation of 14C-MeAIB. The negative relationship between villous tissue accumulation of the system A substrates 14C-MeAIB and 14C-glutamine and placental weight supports previous findings that system A activity adapts according to placental size in normal pregnancy. Future work should focus on assessment of intracellular 14C-MeAIB, 14C-glutamine and 14C-glutamate in FGR, where a small, dysfunctional placenta is observed.

Where applicable, experiments conform with Society ethical requirements