At the recent 89th General Session and Exhibition of the combined IADR, AADR, and CADR meeting in San Diego, March, 2011, numerous studies related to periodontal pathogens and/or disease and innate immunity and pregnancy were presented in oral and poster form.
Four of presentations addressed questions of interest via animal studies and thirteen involved pregnant women. Five of the latter studies concerned behavioral health issues and the remaining addressed, in various ways, the relationship between aspects of periodontal disease, inflammation, or infection and adverse pregnancy outcomes. The Dental Hub presents the results of the four animal experiments associated with pregnancy.
In one mouse study, H.A. Schenkein, et al, sought to assess the relationship of P. Gingivalis to adverse pregnancy outcomes. Porphyromonas gingivalis (P Gingivalis) is a non-motile, gram-negative, rod-shaped, anaerobic pathogenic bacterium that is strongly associated with periodontal disease and bone loss.
In an elegant experiment that involved the immunization of mice with antigen peptide sequences homologous to this bacteria in comparison to a defective mutant antigen coupled with other complicated bioassays’ they were able to show that P Gingivalis might induce pathogenic antigens that could contribute to adverse pregnancy outcomes.
In a second mouse study another periodontal pathogen, Campylobacter Rectus (C Rectus), was assessed for its connection to inflammation and low birth rate. In humans, this periodontal pathogen has been associated with fetal exposure and an increased risk for low-birth weight and prematurity. In- vitro studies have suggested that in mice when C rectus invades placental tissue it induces a localized inflammatory response and upregulation of the TLR4 receptor which is involved in the detection of gram negative bacteria and the activation of what has been termed ‘innate immunity’.
As the authors of this study, R.M. Arce and colleagues of the University of North Carolina, Chapel Hill, point out “it is still unclear whether TLR4 mediates placental inflammatory responses and IUGR onset in vivo”.
What they found was that maternal C Rectus infection did significantly decrease fetal weight and fetal length. They also concluded that cytokine activation may be mediated by the TLR4 receptor during low birth weight and preterm “delivery pathogenesis”.
A third study of mice looked at another aspect of innate immunity and pregnancy. This research focused on what are termed ‘macrophage pattern recognition scavenger receptors (SR-A/CD36). In the murine model for colitis these receptors protect against inflammatory complications.
The authors of this research, H.S. Oz and his colleagues from the Center for oral Health Research, SOD, University of Kentucky, Lexington, hypothesized that this ‘aspect of innate immunity could be essential in bacterial translocation at maternal mucosal surfaces and alterations in this system would increase adverse fetal outcomes”.
They conclude, based on analysis of their data from this mouse study, that the macrophage scavenger receptors are indeed required for fetal protection against microbial attack and that this aspect of maternal ‘innate immunity’ is a crucial aspect of this protection.
Finally, in the last animal study presented at the IADR conference with potential implications for pregnancy, G Knutsen and colleagues from Baylor College of Dentistry in Dallas, Tx and Texas A&M Health Science center assessed the effect of a hormono-dependent underlying mechanism which could explain the fact that the treatment of periodontitis during pregnancy does not appear to improve pregnancy outcomes or eclamptic pregancy. As they note in their abstract, “endothelin signaling is involved in inflammation” as elevated endothelin-A receptor expression has been found to be associated with periodontitis and diseased tissue.
The gene associated with turning on this receptor has also been found to have putative “progesterone response elements”. Given this, the authors analyzed endothelin-A receptor (Ednra) expression in the gingival tissue of pregnant and progesterone-treated mice to see if Ednra was involved in the etiology of periodontitis during pregnancy.
What they found was that Ednra expression increased during pregnancy and progesterone treatment of ovariectomized mice partially recapitulated the effects. They conclude that Ednra may be part of the many molecular hormonal mechanisms promoting the development of periodontitis during pregnancy. They also note that to confirm this possibility, additional studies are necessary.
Taken together, these studies using animal models provide additional evidence of a link between periodontal pathogens and adverse pregnancy outcomes.
Submitted by Jeff Burgess DDS MSD, Editor in Chief