PLACENTAL DYSFUNCTION IN MATERNAL OBESITY — A KEY MECHANISM OF FETAL PROGRAMMING OF METABOLIC SYNDROME
Abstract
The placenta is a critical link between the maternal and fetal bodies and is therefore a central organ to be studied in the context of fetal programming of the metabolic syndrome. Obesity causes placental dysfunction through a variety of mechanisms, including impaired expression of fatty acid transporter genes, esterification enzymes and lipid deposition. The resulting lipotoxic environment, by increasing the levels of a number of proinflammatory markers in both maternal plasma and placenta, activation of placental inflammatory signaling, and upregulation of proinflammatory genes, determines intraplacental functional abnormalities and programs long-term metabolic disorders in the fetus. Evidence of increased placental reactive oxygen species (ROS) levels, protein nitrosylation, altered cytokine concentrations; increased lipid peroxidation with subsequent endothelial dysfunction of the placental vascular network is recorded. The results of studies on the determination of hormone levels in both placental tissues and fetal cord blood in obese women demonstrate various metabolic shifts. Of particular interest is the consideration of sexual dimorphism in the context of fetal programming. There is a definite cascade of differences in the genetic, metabolic, inflammatory profile depending on the sex of the fetus. These changes represent mechanisms that contribute to placental dysfunction and programming of obesity and metabolic diseases in the fetus, which are realized at a later age. However, many aspects of placental dysfunction in maternal obesity require further investigation.
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