Although there is significant interest in elucidating the role of placenta-derived exosomes (PdEs) during pregnancy, the exosomal profile in pregnancies complicated by gestational diabetes mellitus (GDM) remains to be established. The aim of this study was to compare the gestational-age profile of PdEs in maternal plasma of GDM with normal pregnancies and to determine the effect of exosomes on cytokine release from human umbilical vein endothelial cells. A prospective cohort of patients was sampled at three time points during pregnancy for each patient (i.e., 11–14, 22–24, and 32–36 weeks' gestation). A retrospective stratified study design was used to quantify exosomes present in maternal plasma of normal (n = 13) and GDM (n = 7) pregnancies. Gestational age and pregnancy status were identified as significant factors contributing to variation in plasma exosome concentration (ANOVA, P < 0.05). Post hoc analyses established that PdE concentration increased during gestation in both normal and GDM pregnancies; however, the increase was significantly greater in GDM (∼2.2-fold, ∼1.5-fold, and ∼1.8-fold greater at each gestational age compared with normal pregnancies). Exosomes isolated from GDM pregnancies significantly increased the release of proinflammatory cytokines from endothelial cells. Although the role of exosomes during GDM remains to be fully elucidated, exosome profiles may be of diagnostic utility for screening asymptomatic populations.
Although the role of exosomes during PE remains to be fully elucidated, we suggest that the concentration and content of exosomes may be of diagnostic utility for women at risk for developing PE.
Preeclampsia (PE) is one of the main causes of maternal and fetal morbidity and mortality in the world, causing nearly 40% of births delivered before 35 weeks of gestation. PE begins with inadequate trophoblast invasion early in pregnancy, which produces an increase in oxidative stress contributing to the development of systemic endothelial dysfunction in the later phases of the disease, leading to the characteristic clinical manifestation of PE. Numerous methods have been used to predict the onset of PE with different degrees of efficiency. These methods have used fetal/placental and maternal markers in different stages of pregnancy. From an epidemiological point of view, many studies have shown that PE is a disease with a strong familiar predisposition, which also varies according to geographical, socioeconomic, and racial features, and this information can be used in the prediction process. Large amounts of research have shown a genetic association with a multifactorial polygenic inheritance in the development of this disease. Many biological candidate genes and polymorphisms have been examined in their relation with PE. We will discuss the most important of them, grouped by the different pathogenic mechanisms involved in PE.
Hypertensive disorders are a major cause of maternal death. Preeclampsia (PE) affects about 5% of pregnancies and is associated to high cardiovascular death risk. Understanding of its origin and cause is difficult and many etiologies have been proposed. So far, little can be done for real prevention and the only treatment is pregnancy interruption, increasing the child's risk for prematurity complications. Early markers of disease are a promising path for understanding the pathogenesis and developing new strategies for prediction and eventually disease prevention.
Gestational diabetes (GD), defined as carbohydrate intolerance with onset or first recognition during pregnancy, has a prevalence of 7% and is a growing problem worldwide. Infants born to mothers with GD are more likely to be large for gestational age, incur traumatic birth injury, require a stay in the intensive care unit and develop postnatal metabolic disturbances. As the worldwide epidemic of obesity worsens, more women are entering pregnancy with metabolic alterations and preexisting insulin resistance, which is heightened by the hormonal milieu of pregnancy. The Hyperglycemia Adverse Pregnancy Outcome (HAPO) study has clearly shown that GD-related complications correlate with glycemic control. We will review the current understanding of the physiology of GD and the screening and treatment guidelines that are commonly utilized in clinical care. In addition, we will discuss the need for development of multiparametric models combining maternal clinical risk factors and biomarkers early in pregnancy to better stratify and predict risk of GD-related complications and offer targeted intervention.
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