Endocrine Abstracts

Background and aims: The relationship between gestational diabetes mellitus (GDM) and oxidative stress is not well known and the effect of both oxidative and nitrosative stress in GDM placenta and the impact that could have on perinatal morbidity and risk of future complications is still pending to be elucidated. The aim of the study was to evaluate the relationships between maternal and placental tissue levels of markers of nitrosative and oxidative stress and antioxidants in women with GDM, which potentially may have considerable clinical implications in the pathogenesis and/or the evolution of GDM.

Material and methods: Pregnant women (n=78; 53 with GDM, 25 controls), between the 24th and 29th weeks of gestation were enrolled. Both groups were analysed for demographic data, perinatal and obstetrics results and the levels of the markers oxidative stress and antioxidants status were measured (measured in serum or plasma using a commercial kit (Cayman Chemical, Ann Arbor, MI, USA)). Seven placenta GDMs and seven normal placentas were studied. Placental tissue levels of markers of oxidative stress and antioxidant were measured by Western Blotting techniques and Biotin-switch technique has been performed to identify S-nitrosylated protein in placental tissue.

Results: In the univariate analysis control versus patient results were: pre-gestational BMI 23.31±4.2 kg/m² vs 27.13±4.6 kg/m² (P=0.001); weeks at delivery 39.2±3.05 vs 38.9±1.8 (P=0.09); caesarean delivery 12.5% vs 43% (P=0.004); macrosomia 4% vs 9.4% (P=0.6); lipoperoxides (LPO) 2.06±1.00 mol/mg vs 3.14±1.55 mol/mg (P=0.001); catalase 3.23±1.41 nmol/min per ml vs 2.52±1.3 nmol/min per ml (P=0.03); superoxide dismutase (SOD) 0.11±0.04 U/ml vs 0.08±0.01 U/ml (P=0.0003); glutathione peroxidase (GPX) 0.03±0.006 nmol/min per ml vs 0.025±0.006 nmol/min per ml (P=0.01); glutathione reductase (GSH) 0.004±0.002 nmol/min per ml vs 0.004±0.004 nmol/min per ml (P=0.9); and glutathione transferase (GST) 0.0025±0.0012 nmol/min per ml vs 0.0027±0.00017 nmol/min per ml (P=0.7). Multivariate analysis that was performed using non-conditional logistic regression showed catalase might have a protective effect and LPO seems to be a risk factor for GDM development. In GDM placenta, protein expression of catalase (n=0.05), SOD (n=0.03), and GPx (n=0.04) were significantly increased. In addition, an increased S-nitrosylation of catalase (n=0.02), SOD, and GPx has been determinate in GDM placenta comparing with control.

Conclusions: i) An increase in oxidative stress and a decrease in antioxidative defence can be observed in plasma of women with GDM. However, in placental tissue, elevated expression of antioxidant enzymes and an increment of their S-nitrosylation have been found which could be related with regulation of these activity. ii) Results suggest that resistance to oxidative insults generated in placenta by a chronic mild oxidative/nitrosative environment could alleviate the effect of systemic elevation of ROS and RNS. The effect of both oxidative and nitrosative stress in GDM placenta and the impact that could have on perinatal morbidity should be studied more extensively.