EFFECT OF CHRONIC INFECTION ON PLACENTAL DEVELOPMENT

描述(申请人提供)：牙周病是一种慢性、多种微生物的口腔感染，影响高达50%的孕妇。这种口腔感染最近被认为与不良妊娠结局有关。患有活动性慢性感染的孕妇自然流产、先兆子痫和小于胎龄儿的风险增加三到五倍。尽管有动物和人类的数据表明口腔病原体系统性地传播到母体和胎儿的循环以及胎盘，但慢性母体口腔感染扰乱正常妊娠的机制尚不清楚。正常妊娠的维持是以正常的胎盘和胎盘发育为前提的。本研究旨在研究慢性母体口腔感染影响妊娠结局的机制。本研究旨在建立兔口腔病原体慢性母体感染对胎儿生长发育和胎盘发育影响的动物模型。 这一应用的假设是，慢性母体感染口腔病原体会导致这些病原体移位到子宫-胎盘单位，改变植入时母体与胎盘的相互作用，从而损害胎儿的生长。冗余存在于母胎界面，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入侵。慢性母体感染口腔病原体可能会改变使胎盘正常发育所必需的平衡。在具体目标1中，将在兔体内建立远离子宫的慢性母体感染口腔病原体的模型，并用于测量对胎儿生长的影响。在具体目标2中，将确定允许正常着床的母婴保护因素，并比较慢性感染口腔病原体的兔与未感染的兔的胎盘炎症和母体免疫耐受性。胎盘内炎症和免疫耐受生物标志物的存在与否将与胎盘和新生儿体重的恢复或口腔病原体相关。对这些机制的了解可能有助于制定干预措施，以保护胎儿和胎盘免受口腔病原体慢性母体感染造成的损害。

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.