The role of maternal obesity-driven inflammation and adverse pregnancy outcomes in a mouse model of preeclampsia

项目摘要： 怀孕是一种炎症的生理状态。然而，怀孕期间炎症加剧与 不良后果，如先兆子痫（PE）。PE的临床体征包括母体高血压和 妊娠后半期出现蛋白尿。虽然PE在怀孕后期出现，但其起源被认为是 开始在怀孕早期或甚至在受孕之前。重要的是，母亲的高血压只有在 胎盘的分娩;因此，人们普遍认为胎盘形成异常在PE中起着因果作用 发病机制，虽然病因不明。一些母亲的特征，包括肥胖， 是已知的发生PE的危险因素。据推测，母亲肥胖可能有助于提高 炎症和随后的异常胎盘血管发育。其总体目标是， 提出的研究是为了验证这一假设，即由特定的免疫细胞产生的促炎介质 母体脂肪组织内的促血管生成因子减少母体-胎儿界面处的促血管生成因子。我们将进行我们的 使用BPH/5小鼠PE模型的研究。

Project Summary: Pregnancy is a physiological state of inflammation. However, heightened inflammation during pregnancy is linked to adverse outcomes, such as preeclampsia (PE). The clinical signs of PE include maternal hypertension and proteinuria during the second half of gestation. While PE presents later in pregnancy, its origins are thought to begin early in pregnancy or even before conception. Importantly, maternal hypertension only resolves after delivery of the placenta; therefore, it is widely accepted that abnormal placentation plays a causal role in PE pathogenesis, though the etiology of this is unknown. A number of maternal characteristics, including obesity, are known risk factors for developing PE. It is hypothesized maternal adiposity may contribute to heightened inflammation and subsequent abnormal placental vascular development. The overarching goal of these proposed studies is to test the hypothesis that pro-inflammatory mediators produced by specific immune cells within maternal adipose tissue reduce pro-angiogenic factors at the maternal-fetal interface. We will conduct our studies using the BPH/5 mouse model of PE.