Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, C97
Placental sirtuin 1 (SIRT-1) and mammalian target of rapamicyn (mTOR) in the Preobe Study: a protective response for the fetus against the adverse outcomes of maternal obesity?
J. Martino1,2, S. Sebert1, M. T. Segura2, I. Rusanova2, M. C. Martinez-Zaldivar2, L. Garcia-Valdez2, M. C. Padilla3, H. J. McArdle4, H. Budge1, M. E. Symonds1, C. Campoy2
1. Early Nutrition Research Unit and Respiratory Biomedical Research Unit, Academic Division of Child Health, University of Nottingham, Nottingham, United Kingdom. 2. Department of Paediatrics. University Clinical Hospital San Cecilio. Excellence Centre for Paediatric Research, University of Granada, Granada, Spain. 3. Department of Obstetrics and Gynecology. University Clinical Hospital San Cecilio, University of Granada, Granada, Spain. 4. The Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, United Kingdom.
Background: The maternal metabolic environment influences both fetal development and long-term health in the offspring (1). These responses can be modulated by the placenta due, in part, to its capacity to protect the fetus from adverse conditions. Aim: We, therefore, investigated whether maternal body mass index (BMI) influences placental oxidative status as a result of changes in gene expression for SIRT-1 and mTOR. Methods: Pregnant women were recruited at 20 weeks of gestation and classified according to their pre-pregnancy BMI as control (BMI<25kg/m2; n=56), overweight (BMI=25-30kg/m2; n=26) or obese (BMI>30kg/m2; n=21). At delivery, placentae were sampled and SIRT-1 and mTOR gene expression determined using real-time PCR. OxiSelectTM TBARS assay was used as a measure of lipid peroxidation. Data were analysed according to their parametric distribution by Kruskal-Wallis or 1-way ANOVA. Results: Obesity had no effect on gestational length, birth weight, or postnatal morbidity but obese mothers did produce the largest placentae (C=468.4±15.8g; OB=520±29.1g; (p=0.022)). Placental SIRT-1 gene expression showed a 1.5 fold upregulation with obesity (C=88±10; OB=134±19 x10-5 a.u. (p=0.024)) whereas mTOR expression was halved (C=177±18; OB=87±11 x10-4 a.u. (p=0.022)). TBARS concentrations were similar between groups. Discussion and conclusion: Overexpression of the anti-oxidant gene SIRT-1, combined with reduced mTOR in obese mothers, may indicate an enhanced placental anti-oxidative capacity. Surprisingly, higher placental weight was not associated with increased oxidative stress as measured by TBARS concentrations suggesting a placental compensatory response to raised maternal BMI. A follow up study of the offspring is currently being undertaken up to 18 months of age to establish whether obesity in pregnancy is accompanied with longer term responses.
Where applicable, experiments conform with Society ethical requirements