EFFECT OF CHRONIC INFECTION ON PLACENTAL DEVELOPMENT

描述（由申请人提供）：牙周病是一种慢性、多种微生物口腔感染，影响高达50%的孕妇。这种口腔感染最近与不良妊娠结局有关。患有活动性慢性口腔感染的孕妇发生自然流产、先兆子痫和小于胎龄儿的风险增加3 - 5倍。尽管有动物和人类数据证明口腔病原体向母体和胎儿循环以及胎盘的全身传播，但慢性母体口腔感染破坏正常妊娠的机制尚不清楚。正常妊娠的维持取决于正常的胎盘形成和胎盘发育。本申请旨在研究慢性母体口腔感染可能影响妊娠结局的机制。本研究的目的是建立一个兔模型，以研究母亲慢性口腔病原体感染对胎儿生长和胎盘发育的影响。 本申请的假设是，母体慢性感染口腔病原体导致这些病原体易位至子宫-胎盘单位，改变着床时母体-胎盘相互作用，从而损害胎儿生长。红细胞存在于母体-胎儿界面，保护母体补体激活和炎症，从而允许正常的胚胎附着和胎盘侵入。母亲口腔病原体的慢性感染可能会改变胎盘正常发育所需的平衡。在具体目标1中，将在家兔中建立远离子宫的口腔病原体慢性母体感染模型，并用于测量对胎仔生长的影响。在特定目标2中，将在家兔中表征允许正常着床的母体和胎仔保护因子，并将在口腔病原体慢性感染家兔和未感染家兔之间比较胎盘炎症和母体免疫耐受性。胎盘内炎症和免疫耐受的生物标志物的存在或不存在将与胎盘的恢复或口腔病原体和新生儿体重相关。了解这些机制可能有助于制定干预措施，以保护胎儿和胎盘免受因母亲慢性口腔病原体感染而造成的损害。

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.