The Role of Oxidative Stress in the Pathophysiology of Gestational Diabetes Mellitus

Abstract

Normal human pregnancy is considered a state of enhanced oxidative stress. In pregnancy, it plays important roles in embryo development, implantation, placental development and function, fetal development, and labor. However, pathologic pregnancies, including gestational diabetes mellitus (GDM), are associated with a heightened level of oxidative stress, owing to both overproduction of free radicals and/or a defect in the antioxidant defenses. This has important implications on the mother, placental function, and fetal well-being. Animal models of diabetes have confirmed the important role of oxidative stress in the etiology of congenital malformations; the relative immaturity of the antioxidant system facilitates the exposure of embryos and fetuses to the damaging effects of oxidative stress. Of note, there are only a few clinical studies evaluating the potential beneficial effects of antioxidants in GDM. Thus, whether or not increased antioxidant intake can reduce the complications of GDM in both mother and fetus needs to be explored. This review provides an overview and updated data on our current understanding of the complications associated with oxidative changes in GDM.

PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats

“…Excessive production of NO can affect embryo and fetal development and is a marker of a pro-inflammatory state (Lappas et al 2011). In this work, we found increased nitrates/nitrites concentrations, an index of NO production, in the hearts of female and male fetuses of diabetic rats when compared with controls (P!0.01, Fig.…”

“…Diabetes induces a pro-oxidant and pro-inflammatory state in both the non-pregnant and the pregnant states (Calkin & Thomas 2008, Lappas et al 2011. In previous studies, in a mild diabetic rat model during pregnancy we have evaluated and found alterations in PPARa expression and signaling in different fetal organs such as the liver and the lungs (Jawerbaum & White 2010, Martinez et al 2011a).…”

The effect of pre-existing maternal obesity on the placental proteome: two-dimensional difference gel electrophoresis coupled with mass spectrometry

“…Animal models have been very useful to demonstrate that increases in reactive oxygen species (ROS), together with increases in reactive nitrogen species, are clearly related to the induction of malformations in the fetus (Lappas et al 2011). In this study, we found increased expression of proteins that involved in the generation of ROS as well as increased expression of proteins with antioxidant properties.…”

“…Oxidative stress disturbs placental function leading to perpetrations in fetal growth and development (Lappas et al 2011). Animal models have been very useful to demonstrate that increases in reactive oxygen species (ROS), together with increases in reactive nitrogen species, are clearly related to the induction of malformations in the fetus (Lappas et al 2011).…”

A gestatiós diabetes mellitus súlyossága befolyásolja a három évvel a szülést követően mért microvascularis diszfunkció mértékét, amely kapcsolatban állhat az emelkedett szisztémás oxidatív stresszel

“…Később a lipidperoxidáció egyéb markereinek emelkedését -például 4-hidroxinonenal (4-HNE), TBARS (tiobarbiturát reaktív anyagok) és LOOH (lipidhidroperoxid) -is kimutatták. A placenta szöveteiben is emelkedett oxidatív stresszt találtak; magasabb xantinoxidáz-expresszió, MDA-és 4-HNE-szintek jellemzik a GDM-es placentát [6]. Korábbi tanulmányainkban kimutattuk, hogy a cardiovascularis kockázat becslésére is használható microvascularis endothelfunkciós vizsgálat, a posztokkluvíz reaktív hyper aemia (PORH) teszt során, 3 évvel a szülést köve-tően, a korábban GDM-es anyák reakciókészsége szignifi kánsan elmarad az egészséges terhesekhez képest [7].…”