Martino, Jole
(2013)
Metabolic alterations induced by high maternal BMI and gestational diabetes in maternal, placental and neonatal outcomes.
PhD thesis, University of Nottingham.
Abstract
Maternal obesity and diabetes increase the risk of delivering large for gestational age infants (LGA), who have higher risk of long term obesity or metabolic syndrome [1]. As the underpinning mechanisms of how fetal growth is regulated by the placenta remain unclear [2], this thesis has investigated placental responses to high maternal BMI and gestational diabetes.
Spanish pregnant women recruited at 20 gestational weeks were classified according to pre-pregnancy BMI as control (BMI<25kg/m2; n=59), overweight (BMI=25-30kg/m2; n=29) or obese (BMI>30kg/m2; n=22), and gestational diabetes status (GDM) classified at 28 weeks. Maternal anthropometry and gestational weight gain (GWG) were measured during pregnancy. Placenta, cord blood, newborn antrophometry and infant weight were sampled or measured. Expression of genes involved in placental energy sensing pathways, folate transporters and DNA methylation was determined using real-time PCR, and placental triglyceride concentrations, lipid peroxidation and genomic DNA methylation patterns measured. Data were analysed according to their parametric distribution by Kruskal-Wallis or 1-way ANOVA.
Despite lower GWG, a greater proportion of obese women exceeded recommended weight gain [3], had higher placental weight and increased numbers of LGA infants. Maternal hyperinsulinaemia and hyperglycaemia with obesity were accompanied by unchanged placental IGFR1 and ISR1 expression, similar cord blood glucose and triglyceride concentrations. Placental mTOR was halved with obesity, whilst SIRT1 and UCP2 gene expression were 1.8 and 1.6 fold upregulated respectively with no differences in TBARS concentrations. Hyperleptinaemia in obese women resulted in unchanged placental leptin and leptin receptor expression, but higher cord blood leptin and monocyte concentrations with placental hypermethylation of genes involved in the immune response. Lower folate concentrations in obese mothers led to similar cord blood folate, and decreased placental FRα, but raised DNMT1, mRNA expression. No major differences were observed with GDM, probably due to small sample size.
In conclusion, it appears that the placenta can protect the fetus of obese women by increasing antioxidant capacity, compensating for maternal hyperglycaemia and lower folate. However, maternal obesity was associated with enhanced cord blood leptin and monocyte concentrations, increased placental weight and more LGA delivery, leaving infants at ongoing risk of increased adiposity and inflammation. Therefore, current studies are currently exploring these interacting aspects.
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