Influence of gestational weight gain on placental oxidative stress in women with normal pre-pregnancy body mass index

Abstract Background: Body mass index (BMI) has long been used as a well-known risk factor for assessing the presence of an inappropriate gestational weight gain (GWG) and their potential repercussions on maternal-fetal axis during pregnancy and postpartum, especially for women with overweight and obesity. However, the potential role that the placenta plays on pregnancy outcomes has not been considered so far, particularly in those women that initiate with a normal-range BMI. We aim to examine the impact of GWG on redox state biomarkers in full-term human placentas from uncomplicated pregnant women with normal pregestational BMI. Methods: 25 full-term pregnancies were chosen among a total of 94 after fulfilling the required study inclusion criteria, including mandatory normal singleton pregnancies and scheduled caesarean sections. The selected pregnant women were subsequently categorized as insufficient (<11 Kg), recommended (11-16 Kg) and excessive (>16 Kg), according to the weight gained during gestation for a normal pregestational BMI (18,5-24,9 Kg/m2), as indicated in the clinical guidelines revised and published by the IOM in 2009. At delivery, fresh placental villi were isolated and subjected to measure universal indicators of oxidative damage (carbonyl groups and NADPH oxidase activity) and antioxidant activity (superoxide dismutase [SOD] and antioxidant capacity parameters) by molecular biology techniques. Results: We significantly report an elevated presence of oxidized proteins (carbonyl groups), along with a high activity of the NADPH oxidase enzyme in agreement with an increasing rate of GWG, being more accentuated above 11 kg. Conversely, we also show an overall decrease in both SOD and other antioxidant defense activity in relation to increased weight gain in pregnancy. Conclusions: Our findings reveal the presence of severe oxidative damage, accompanied by a decline in antioxidant function, in those placentas from healthy pregnancies that achieved a GWG within the recommended range associated with pregnancy “good outcomes” for a normal pregestational BMI. Thus, GWG could be a key “unrecognized” maternal factor in the development of a redox impairment in human placenta, and consequently, in the fetal programming of metabolic disease during pregnancy and later in life.