It is well documented that endotoxins can elicit birth complications in pregnant animals and humans. These complications include spontaneous abortions, premature delivery, low birth weight, intrauterine fetal death, and congenital malformations. The central hypothesis of this investigation is that the indigenous gram-negative bacterial flora associated with the oral cavity and/or the gut may play a role in birth complications in humans. We hypothesize that endotoxin, which is contained in high concentrations in both the oral periodontal flora and in the gut, may mediate abnormal pregnancy outcomes (APOs), especially in the presence of periodontal disease or increased penetration of endotoxin (lipopolysaccharide, LPS) at mucosal membranes. We propose experiments using the pregnant hamster model to determine how various routes, types, dosages and frequency of LPS challenges influence pregnancy outcome, mediator production and immune sensitization. Animals will be challenged with Bacteroides gingivalis (B.g.) either as whole cells, heat-killed or isolated LPS prior to mating and/or during pregnancy. Challenge will be either intravenously, by inoculation into a previously implanted subcutaneous tissue chamber, by oral periodontal infection model or by gastric intubation. We will determine the effects of various LPS exposure routes and dosage regimens on fetal weight, viability and frequency of malformation. Bacterial and LPS specific antibody responses will be determined in maternal serum, chamber exudate and colostral whey by ELISA and transimmunoblot techniques, measuring lgG, lgM, lgA and secretory lgA (slgA). Furthermore, we plan to determine if selected LPS-induced secondary mediators are present in the maternal serum, chamber exudate or the amnionic fluid. We will examine these fluids for the presence of lipid mediators including the prostaglandins and thromboxanes, and the monokine, tumor necrosis factor (TNF). The influence of immune sensitization on LPS-induced APOs will also be examined by passive immunization using antibody from immunized animals and by performing adoptive transfer of splenocytes from sensitized animals to pregnant animals prior to LPS challenge. By performing these experiments in C3H, LPS responsive and LPS non-responsive congenic mouse strains, the effects of genetically-determined LPS responsiveness on LPS elicited APOs will be determined and correlated with changes in inflammatory mediators.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD026652-03
Application #
3328188
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1990-08-01
Project End
1993-07-31
Budget Start
1991-08-01
Budget End
1992-07-31
Support Year
3
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Dentistry
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Horton, Amanda L; Boggess, Kim A; Moss, Kevin L et al. (2010) Periodontal disease, oxidative stress, and risk for preeclampsia. J Periodontol 81:199-204
Horton, Amanda L; Boggess, Kim A; Moss, Kevin L et al. (2009) Maternal periodontal disease and soluble fms-like tyrosine kinase-1 expression. J Periodontol 80:1506-10
Horton, Amanda L; Boggess, Kim A; Moss, Kevin L et al. (2008) Periodontal disease early in pregnancy is associated with maternal systemic inflammation among African American women. J Periodontol 79:1127-32
Picklesimer, Amy H; Jared, Heather L; Moss, Kevin et al. (2008) Racial differences in C-reactive protein levels during normal pregnancy. Am J Obstet Gynecol 199:523.e1-6
Ruma, Michael; Boggess, Kim; Moss, Kevin et al. (2008) Maternal periodontal disease, systemic inflammation, and risk for preeclampsia. Am J Obstet Gynecol 198:389.e1-5
Champagne, C M; Madianos, P N; Lieff, S et al. (2000) Periodontal medicine: emerging concepts in pregnancy outcomes. J Int Acad Periodontol 2:13-Sep
Offenbacher, S; Jared, H L; O'Reilly, P G et al. (1998) Potential pathogenic mechanisms of periodontitis associated pregnancy complications. Ann Periodontol 3:233-50
Offenbacher, S; Beck, J D; Lieff, S et al. (1998) Role of periodontitis in systemic health: spontaneous preterm birth. J Dent Educ 62:852-8
Salvi, G E; Yalda, B; Collins, J G et al. (1997) Inflammatory mediator response as a potential risk marker for periodontal diseases in insulin-dependent diabetes mellitus patients. J Periodontol 68:127-35
Salvi, G E; Collins, J G; Yalda, B et al. (1997) Monocytic TNF alpha secretion patterns in IDDM patients with periodontal diseases. J Clin Periodontol 24:8-16

Showing the most recent 10 out of 18 publications