Carbohydrate receptors, preterm labor, and periodontitis

Epidemiological studies suggest that pregnant women with periodontitis experience a moderate risk of preterm labor and low-birth-weight infants. However, the molecular mechanisms underlying this association remain unknown. Bacterial infections and host inflammatory responses initiated by invading bacteria, such as those observed in the pathogenesis of periodontitis, are strongly associated with preterm labor. Various carbohydrate structures assembled by an array of glycosyltransferases mediate bacterial attachment and leukocyte trafficking. I hypothesized that mucin-coated oral and uterine cavities present similar carbohydrate motifs that specify bacterial ecology and leukocyte recruitment in both regions. As a corollary to this theory, I proposed that certain individuals express oligosaccharides that make them susceptible to both periodontitis and preterm labor. I chose laboratory mice as a model system in which to test these suppositions. The first part of the project profiled glycosylation-related genes in the mouse uterus and major salivary glands. I conducted a global analysis of glycosylation-related gene expression patterns in these regions. The study design took into consideration potential effects from the ovarian hormones estrogen and progesterone. The results revealed that both the uterus and the salivary glands contained comprehensive glycosylation machinery enabling the construction of a complex glycome. Significantly, I noted about 300 glycosylation-related genes that were differentially regulated by estrogen and/or progesterone in the mouse uterus, but not in major salivary glands. For a subset of genes, I confirmed the glycoarray data at the mRNA level by quantitative PCR and at the protein level by immunolocalization. In the second part of the project, a bank of lectins and antibodies that recognize specific oligosaccharide structures was used to characterize the glycans expressed in mouse uterine and salivary tissues. Specialized carbohydrate structures that govern bacterial and leukocyte adhesion were detected in both regions. Many of these carbohydrate motifs were differentially regulated by estrogen and/or progesterone in the mouse uterus, as well as in major salivary glands. The information obtained from this project serves as an important prerequisite for developing the mouse as a powerful model system to study the association of periodontitis and preterm labor in the context of carbohydrate-mediated cell-cell adhesion