Viral pathogenesis of chronic inflammatory lesions of the placenta

项目总结 早产和宫内发育受限在美国是严重的公共卫生问题， 分别影响10%和3-9%的新生儿。这些不良妊娠结局会增加罹患 死亡率和终生疾病，以及每年260亿美元的巨额货币成本。 宫内/胎盘炎症导致了一半以上的早产。大部分研究都与 TO胎盘炎症主要集中在急性炎症过程，通常是由细菌驱动的 羊膜腔内感染，对引发和维持的触发因素或机制知之甚少 慢性胎盘炎(CPI)。众所周知，一些CPI与病毒感染有关，例如 巨细胞病毒，但在大多数情况下，CPI的病因仍不清楚。我们假设大多数CPI是一个 胎盘对病毒感染的慢性炎症反应。我们将全面分析胎盘组织 以确定病毒和抗病毒炎症特征是否与CPI相关。 此外，我们将检测怀孕期间采集的孕妇血液，以确定是否可以识别病毒 和/或将预测CPI发展的主机信号。最后，我们将检测新生儿脐带血中的 病毒感染的存在或宿主信号与胎盘或孕妇血液中看到的一致。本研究 有可能导致CPI的预测性或诊断性测试的开发，它将帮助我们 了解CPI是如何触发和发展的，这样我们最终可能能够设计一种预防性或 治疗性治疗。最终，我们预测和/或预防CPI的能力将改善怀孕结果和 儿童健康。

PROJECT SUMMARY Preterm birth and intrauterine growth restriction are significant public health problems in the United States, affecting 10% and 3-9% of births, respectively. These adverse pregnancy outcomes result in increased risk of mortality and lifelong morbidities, in addition to substantial monetary costs of >$26 billion annually. Intrauterine/placental inflammation contributes to more than half of preterm birth. Much of the research related to placental inflammation has focused on acute inflammatory processes, which are typically driven by bacterial infections in the amniotic cavity, and little is known about the triggers or mechanisms that initiate and sustain chronic placental inflammation (CPI). It is well known that some CPI is associated with viral infection, such as cytomegalovirus, but in most cases, the etiology of CPI remains unknown. We hypothesize that most CPI is a chronic inflammatory reaction to viral infection in the placenta. We will comprehensively analyze placental tissue from pregnant women to determine whether viruses and antiviral inflammatory profiles are associated with CPI. Furthermore, we will test maternal blood collected during pregnancy to determine whether we can identify a viral and/or host signal that will predict development of CPI. Lastly, we will test neonatal umbilical cord blood for the presence of viral infection or host signal consistent with that seen in the placenta or maternal blood. This study has the potential to lead to the development of a predictive or diagnostic test for CPI, and it will help us to understand how CPI is triggered and progresses so that we may ultimately be able to design a preventative or therapeutic treatment. Ultimately, our ability to predict and/or prevent CPI will improve pregnancy outcomes and child health.