Proceedings of The Physiological Society
University of Manchester (2010) Proc Physiol Soc 19, PC245
Raised maternal body mass index (BMI) differentially alters amino acid transporter activity in human placenta.
A. Ditchfield1, T. A. Mills1, M. Wareing1, C. P. Sibley1, S. L. Greenwood1
1. Maternal and Fetal Health Research Centre, The University of Manchester, Manchester, United Kingdom.
Fig 1A: Placental system β activity is negatively related to maternal BMI. Fig 1B: Placental system A and system β activities are positively related in women with normal BMI (closed circles; regression line) but unrelated in women with raised BMI (25-49.9; open circles). AUC =area under curve 30-120 min; least squares linear regression
Maternal obesity is associated with fetal complications including stillbirth, developmental abnormalities, excessive or restricted fetal growth and predisposition to obesity and cardiovascular disease in later life1. Abnormal fetal growth and development in women with raised BMI may have its origin in altered placental nutrient transport. We tested the hypothesis that placental amino acid transporter system A (transports small neutral amino acids, sustains fetal growth2) and system β (transports taurine, essential for fetal organogenesis3) activities are altered in women with raised BMI. Maternal BMI was recorded at the first antenatal visit (<12 weeks) and women grouped as normal BMI (18.5-24.9; n=17), overweight (25-29.9; n=12) or obese (class I/II 30-39.9; n=7: class III 40-49.9; n=4). Placentas were collected at term following normal pregnancy. Placental weight was recorded and villous tissue sampled to determine system A and β activity as the Na+-dependent uptake of 14C methylaminoisobutyric acid (MeAIB; non-metabolised substrate of system A) and 3H taurine respectively. Uptake was measured in control or Na+-free Tyrode’s buffer (choline Cl replaced NaCl) at 30, 60, 90 and 120 min. The Na+-dependent component was expressed per mg tissue protein and analysed by least squares linear regression. Most women (34/40) delivered appropriately sized babies for gestational age; 5 women (3 normal, 2 raised BMI) had large infants (birthweight >90th centile) and 1 overweight mother delivered a growth-restricted infant (birthweight <5th centile). Overall, maternal BMI was unrelated to birthweight, placental weight or fetal:placental weight ratio. Na+-dependent 14C MeAIB and 3H taurine uptake was linear over 30-120 min (p<0.0001; n=40). System A activity did not differ between BMI categories and was not related to BMI expressed as a continuous variable (linear regression p=0.62). In contrast, placental system β activity was significantly lower in obese (class III) women compared with women of normal BMI (log linear regression 30-120 min; p<0.0009) and there was a significant negative relationship between system β activity and maternal BMI (Fig 1A). System A and system β activity were positively related in normal weight women, but not in women with raised BMI (Fig 1B). Conclusions: Reduced system β activity in women with class III obesity could inhibit placental taurine transfer and compromise fetal development through taurine deficiency. The loss of relationship between system A and system β activity in women with raised BMI suggests an imbalance in placental nutrient transporter activity may increase susceptibility of obese women to poor fetal outcome. Future studies will explore links between the obesogenic environment and reduced placental taurine transport.
Where applicable, experiments conform with Society ethical requirements