Diabetes or Obesity in Pregnancy and Oxidative Stress in the Offspring

Abstract

Abstract During normal gestations, oxidant molecules have many physiological functions, which are summarized in controlling cellular fate and signaling, thus playing a crucial role in pregnancy development. Oxidative stress (OS) arises when the production of reactive oxygen species (ROS) overwhelms the intrinsic antioxidant defenses. OS is implicated in the pathophysiology of many complications of human pregnancy, such as gestational diabetes mellitus (GDM), in which both free-radical production and antioxidant defenses are disrupted. The mechanisms of such kind of relation between OS and gestational diabetes have been analyzed during the years. Hyperglycemia leads to an increased production of ROS through different metabolic pathways. Thus, when ROS production increases, transcription factors (TFs) such as nuclear factor-κB will become activated and lead to insulin resistance due to the impairment of insulin signaling. Moreover, TFs may also induce proinflammatory cytokine expression, such as interleukin-6, tumor necrosis factor-α, and monocyte chemoattractant protein-1, which are able to cause insulin resistance directly or indirectly. Placental tissue, fetuses and preterm infants are greatly susceptible to OS damage because of the organ and functional immaturity. ROS were first suggested to be related to diabetes-induced teratogenicity by Eriksson and Borg. Indeed, during the period of organogenesis, ROS attack on DNA represents the first step involved in mutagenesis, carcinogenesis, and fetal programming. Therefore, pregnancies complicated with GDM have miscarriage, PROM, and other anomaly rates higher than nondiabetic gestation. Furthermore, children of GDM mothers are at high risk to develop obesity and type 2 diabetes later in life. The management of OS, along with tight glycemic control, could be beneficial, both preconceptionally and during pregnancy, in women with GDM. However, whether an antioxidant supplementation or a diet rich in antioxidants can prevent the consequences of OS in the offspring or not is yet to be elucidated.