INTRODUCTION: In the UK it is estimated that 20% of pregnant women are obese (body mass index BMI≥30kg/m2) at their first antenatal appointment. Maternal obesity increases the risk of gestational diabetes mellitus (GDM), a condition of severe insulin resistance and hyperglycemia. Both GDM and maternal obesity increase the risk of fetal mortality and morbidity and are associated with elevated placental oxidative stress. Animal studies have shown that taurine supplementation in pregnancy protects against diabetes-induced oxidative stress in mother and embryo1. We have shown that the activity of TauT, the protein that transports taurine into the placenta, is significantly lower in obesity than in normal pregnancy2. Taurine is an antioxidant amino acid and a reduction in placental taurine uptake could contribute to elevated oxidative stress in obesity and GDM. Here we test the hypothesis that placental TauT activity is lower in women with GDM as compared to normal pregnancy. METHODS: Placentas were collected at term from women with GDM and women experiencing normal pregnancy (NP). BMI was recorded at antenatal booking (12 weeks gestation) to allow separation of women into obese (BMI≥30) and non-obese (BMI 18.5-29) groups. TauT activity was determined by measuring Na+-dependent uptake of 3H-taurine into freshly isolated placental villous tissue over 120min (fmol/mg protein). TauT protein expression in membrane-enriched placental homogenates was assessed by Western blotting. Nitrocellulose membranes were re-probed for β-actin to normalise TauT expression. Data are presented as medians and analysed by Mann Whitney. RESULTS: In non-obese women, placental TauT activity was significantly lower in GDM compared to NP (2335 and 4137 respectively, p<0.03, n=7 in each group). In common with our earlier observations2, in NP TauT activity was lower in placentas of obese (2590, n=3) compared to non-obese women (4137, n=7). However, TauT activity did not differ in obese (n=6) and non-obese (n=7)women experiencing GDM (p>0.05). Following Western blot analysis, TauT protein was observed at 70kDa consistent with previous reports in human placenta2. In non-obese women, there was no difference in the normalised density of immunoreactive signals between NP and GDM (n=7 in each group). CONCLUSIONS: Placental TauT activity, but not expression, is lower in non-obese women with GDM compared to NP. We have previously shown that the reduction in TauT activity in obesity is not associated with a change in protein expression2, suggesting that post-translation regulation of transporter activity is common to both conditions. Experiments are ongoing to determine the mechanism of TauT down-regulation and to explore a link between reduced TauT activity and elevated placental oxidative stress in obesity and GDM.
Obesity – A Physiological Perspective (Newcastle, UK) (2014) Proc Physiol Soc 32, PC042
Poster Communications: Human placental taurine transporter activity is reduced in pregnancies complicated by gestational diabetes mellitus
F. Hey1, S. L. Greenwood1, M. Price1, M. Desforges1
1. Maternal and Fetal Health Research Centre, University of Manchester, Manchester, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.