EFFECT OF CHRONIC INFECTION ON PLACENTAL DEVELOPMENT

慢性感染对胎盘发育的影响

• 批准号: 6719097
• 负责人: Kim A Boggess
• 金额: $ 12.6万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-13 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6719097
• 关键词: Bacteroides gingivalis; amniotic fluid; biomarker; embryo /fetus; embryogenesis; growth /development; histology; humoral immunity; immunocytochemistry; in situ hybridization; laboratory rabbit; northern blottings; oral bacteria; periodontium disorder; placenta; placental transfer; polymerase chain reaction; pregnancy circulation; prenatal stress; terminal nick end labeling; western blottings

DESCRIPTION (provided by applicant): Periodontal disease is a chronic, polymicrobial oral infection that affects up to 50% of pregnant women. This oral infection has recently been associated with adverse pregnancy outcome. Pregnant women with active chronicoral infection have a three to five-fold increased risk for spontaneous miscarriage, preeclampsia, and small-for-gestational age infants. The mechanisms by which chronic maternal oral infection disrupts normal pregnancy is unknown, although there are animal and human data to demonstrate systemic dissemination of oral pathogens to the maternal and fetal circulation, and to the placenta. Maintenance of normal pregnancy is predicated by normal placentation and placental development. This application seeks to study the mechanisms that chronic maternal oral infection could affect pregnancy outcome. The purpose of this investigation is to develop a rabbit model to study the effects of chronic maternal infection with oral pathogens on fetal growth and placental development. The hypothesis of this application is that chronic maternal infection with oral pathogens results in translocation of these pathogens to the utero-placental unit, altering maternal-placental interaction at the time of implantation, thus impairing fetal growth. Redundancy exists at the maternal-fetal interface that protects against maternal complement activation and inflammation, which allows normal embryo attachment and placental invasion. Chronic maternal infection with oral pathogens may alter the balance necessary to allow normal placental development to occur. In Specific Aim 1, a model of chronic maternal infection with oral pathogens, distant from the uterus, will be developed in the rabbit and used to measure the effect on fetal growth. In Specific Aim 2, maternal and fetal protective factors that allow normal implantation will be characterized in the rabbit, and placental inflammation and maternal immune tolerance will be compared between rabbits chronically infected with oral pathogens and those uninfected. The presence or absence of biomarkers of inflammation and immune tolerance within the placenta will be correlated with recovery or oral pathogens from the placenta and newborn weight. Understanding of these mechanisms may assist in the development of interventions to protect the fetus and placenta from damage as a result of chronic maternal infection with oral pathogens.

描述（由申请人提供）：牙周疾病是一种慢性多菌病口腔感染，影响多达50％的孕妇。这种口腔感染最近与不良妊娠结局有关。患有活跃慢性感染的孕妇的自发性流产，先兆子痫和小胎龄的婴儿的风险增加了三到五倍。慢性母亲口腔感染破坏正常妊娠的机制尚不清楚，尽管有动物和人类数据可以证明对母体和胎儿循环以及胎盘的全身传播口腔病原体的传播。正常妊娠的维持是通过正常胎盘和胎盘发育来取决的。该应用旨在研究慢性母体口腔感染可能影响妊娠结局的机制。这项研究的目的是开发一种兔模型，以研究口腔病原体对胎儿生长和胎盘发育的慢性母体感染的影响。 该应用的假设是，口腔病原体的慢性母体感染会导致这些病原体转移到子宫位单位，从而改变了植入时的母体 - 定位相互作用，从而损害了胎儿生长。冗余存在于产妇界面，可预防母体补体激活和炎症，这允许正常的胚胎附着和胎盘侵袭。口腔病原体的慢性母体感染可能会改变允许正常胎盘发育的必要平衡。在特定的目标1中，将在兔子中开发出远离子宫的慢性母体感染模型，并用于衡量对胎儿生长的影响。在特定的目标2中，将在兔子中表征允许正常植入的母体和胎儿保护因子，并且将在长期感染口腔病原体的兔子和未感染的兔子之间比较胎盘炎症和孕妇免疫耐受性。胎盘内炎症和免疫耐受性的生物标志物的存在或不存在与胎盘和新生体重的恢复或口腔病原体有关。了解这些机制可能有助于开发干预措施，以保护胎儿和胎盘免受口腔病原体的慢性母体感染的损害。