Disruption of the feto-maternal transfer zone via maternal obesity

育龄妇女的肥胖人数正在增加，因产妇肥胖而导致的怀孕人数也在增加。几项研究揭示了母亲肥胖与胎盘功能障碍风险之间的联系，而胎盘功能障碍反过来又会对胎儿发育产生负面影响。在本项目中，我们旨在研究母体肥胖诱导主要由IL-6和tnf - α介导的系统性炎症反应，从而降低胎盘的胎母转移能力，从而降低胎儿供应的假设。我们的数据表明，肥胖引起的炎症改变了内皮细胞的稳态，破坏了胎母转移区胎盘细胞之间的细胞间连接。在这项资助中，我们将确定细胞因子介导的胎盘损伤的潜在分子机制，并在我们的母体肥胖小鼠模型中，我们将分析怀孕期间的营养干预或直接阻断IL-6和tnf - α是否可以防止胎母转移区血管改变和细胞间不稳定，从而改善胎儿发育。我们的研究将使我们能够确定有效的预防和治疗策略的分子靶点，以对抗母亲肥胖导致的胎盘功能障碍。

Obesity in women at reproductive age is increasing, and so is the number of pregnancies complicated by maternal obesity. Several studies revealed a connection between maternal obesity and the risk to develop a placental dysfunction, which in turn negatively affects fetal development. In this project we aim to study the hypothesis that maternal obesity induces a systemic inflammatory reaction which is mainly mediated by IL-6 and TNF-alpha, and which reduces the feto-maternal transfer capacity of the placenta and hence, fetal supply. Our data indicate that the obesity-induced inflammation alters endothelial cell homeostasis and destabilizes the intercellular connections between placental cells located within the feto-maternal transfer zone. In this grant we will determine the underlying molecular mechanisms of cytokine mediated placental damage and in our mouse model of maternal obesity we will analyse whether a nutritional intervention during pregnancy or a direct block of IL-6 and TNF-alpha may prevent vascular alterations and intercellular destabilisation in the feto-maternal transfer zone to improve fetal development. Our study will allow us to determine molecular targets for effective preventive and therapeutic strategies against placental dysfunction as a consequence of maternal obesity.