Abstract

Gestational diabetes mellitus (GDM) is a human pregnancy disease characterized by elevation of glucose levels (i.e., hyperglycemia) responsible for a several adverse perinatal outcomes included macrosomia, fetal hypoglycemia, requirement of neonatal intensive care and neonatal mortality, among others. Estimation of the epidemiological impact of GDM has indicated that at least 1 out of 10 pregnant woman is being affected by GDM worldwide. In addition, GDM causes not only short-term complication in both mother and fetus, but also is associated with elevated risk for long-term complication such as cardiovascular disease, obesity and diabetes. Even though it is not feasible to exclude the genetic component in the elevated risk for metabolic/cardiovascular disease later in life, the general agreement is that hyperglycemia generates an adaptive response in the fetus addressing to control the glucose level, characterized by hyperinsulinemia. Part of this adaptive response, might also include the elevation in the placental consumption of glucose and enhancement of the feto-placental blood flow, especially in fetus large-for-gestational age (LGA). On the other hand, due to lack of innervation in the placenta, the vascular tone is controlled by the regulation of the synthesis and release of vasoactive substances from the endothelium like vasoactive molecules, nitric oxide, adenosine, prostaglandin, among others. Interestingly, vasoactive molecules may also regulate endothelial proliferation and migration, suggesting that they also affect the vessel formation (i.e., angiogenesis). In this regard, several studies have shown that placenta from GDM is characterized by hypervascularization and elevation in the pro-angiogenic signals including the secretion and activity of the vascular endothelial growth factor (VEGF). In addition, hyperglycemia also generates a status of oxidative stress, where free radicals derived from oxygen (ROS) induces changes in the endothelial cell membranes producing an elevation in the cell permeability. Therefore, it is feasible that the adaptive response -useful for surviving in a hostile medium (i.e, hyperglycemia) - may be imprinting in the fetus and once he/she is exposed to other different conditions after delivery, this response might constitute a risk factor for developing metabolic diseases. In this chapter, we will review the available literature focus on the role of feto-placental endothelial dysfunction as the possible main factor in the generation of short-term complication during GDM and speculate how it may program the response of the sibling exposed to GDM.