Gestational diabetes mellitus (GDM) and obesity in pregnancy (OP) are pathological conditions associated with placenta vascular dysfunction coursing with metabolic changes at the fetoplacental microvascular and macrovascular endothelium. These alterations are seen as abnormal expression and activity of the cationic amino acid transporters and endothelial nitric oxide synthase isoform, that is, the “endothelial L-arginine/nitric oxide signalling pathway.” Several studies suggest that the endogenous nucleoside adenosine along with insulin, and potentially arginases, are factors involved in GDM-, but much less information regards their role in OP-associated placental vascular alterations. There is convincing evidence that GDM and OP prone placental endothelium to an “altered metabolic state” leading to fetal programming evidenced at birth, a phenomenon associated with future development of chronic diseases. In this paper it is suggested that this pathological state could be considered as a metabolic marker that could predict occurrence of diseases in adulthood, such as cardiovascular disease, obesity, diabetes mellitus (including gestational diabetes), and metabolic syndrome. 1. Introduction Pregnancy is a physiological state with a complex anatomical and functional interaction between mother and fetus . When this interaction is not a success, the mother, the fetus, or both exhibit functional impairments. Complications of pregnancy are important causes of maternal mortality, where gestational diabetes mellitus (GDM) and obesity of the mother in pregnancy (OP) are major obstetric pathologies. Fetal-maternal interaction could result in metabolic disturbances leading, for example, to placental and endothelial dysfunction [2, 3]. Endothelial dysfunction is defined as an altered capacity of the endothelium to take up and metabolize the cationic amino acid L-arginine, the substrate for nitric oxide (NO) synthesis via NO synthases (NOS) [4, 5]. Interestingly, it is reported that GDM and OP are pathological conditions associated with altered L-arginine transport and NO synthesis (i.e., the “L-arginine/NO signalling pathway”), probably due to altered uptake and metabolism of adenosine [6, 7], an endogenous nucleoside acting as vasodilator in most vascular beds [8, 9]. These pathophysiological characteristics are considered key in the establishment of a “programmed state” of the developing fetus (i.e., “fetal programming”). This concept refers to the impact of abnormal intrauterine conditions on the development of diseases in adulthood and becomes a key mechanism
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