Periodontitis and Preterm Birth:Nonhuman Primate Model

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Current human epidemiologic reports indicate a positive association between preterm birth/low birth weight (PTB/LBW) neonates and periodontal disease prevalence in the mother. Sixty percent of infant mortality (not attributable to congenital/anatomical defects) is linked with PTB/LBW. It is the objective of this project to investigate potential mechanisms of the association between PTB/LBW and periodontitis in an in vivo model system. The baboon, Papio anubis, which has a >95 percent genetic homology to humans will be used to investigate Aims testing hypotheses that: (1) the incidence and severity of periodontitis results in an increased incidence of PTB/LBW neonates; (2) the progression of periodontitis is characterized by an increase in pathogenic subgingival microbial species and systemic expression of plaque pathogenicity, which correlate with an increased incidence of PTB/LBW neonates; and (3) the progression of periodontitis is characterized by local and systemic inflammatory biomarkers, which correlate with an increased incidence of PTB/LBW neonates. 400 female baboons, housed at the Southwest Foundation for Biomedical Research (SFBR), a NIH Regional Primate Center, will be randomized into two groups. Following baseline sample collection (blood, crevicular fluid (GCF), subgingival plaque, clinical assessment) from all baboons, ligature will be placed (one maxillary/one mandibular quadrant; 6 molar teeth) in the experimental group (n=200). Both groups will then be introduced to males. Pregnancy will be confirmed and gestational age determined using ultrasound at approximately 3 months. Oral samples will be collected at this time point, followed by placement of ligatures on the contralateral maxillary and mandibular quadrants of the experimental group to extend the exposure variable (i.e. periodontitis). Animals will be sampled at approximately 30 days following the completion of the pregnancy and ligatures removed. In both experimental and control groups, dates of birth and post-natal weights will be obtained within 14 days of birth. Blood IGCF samples will be assayed for acute phase reactants and endotoxin activity. Sera will also be analyzed for IgG antibody to oral microorganisms. Differences in clinical and laboratory parameters will be assessed between outcome (PTB/LBW vs. normal neonates) and between groups (experimental vs. control). Results from this investigation will describe mechanisms of this linkage and contribute to the development of therapeutic and clinical intervention strategies.