Porphyromonas ingivalis (Pg) is a common periodontal pathogen of humans that is also strongly associated with low birth weight, intrauterine growth restriction, preeclampsia, and spontaneous preterm birth. Epidemiologic studies suggest that Pg may promote adverse pregnancy outcomes through the direct pathway via hematogenous delivery into the uterine and fetal compartment. However, the circumstances or mechanisms whereby Pg promotes obstetric disease remains elusive, and current approaches to treat/prevent periodontal disease during pregnancy have had limited efficacy in reducing the incidence of preterm birth. Recent work by our group indicates that Pg can translocate from the oral cavity and colonize the non-pregnant uterus. Further, during pregnancy, Pg preferentially colonizes the deep placental bed of pregnant rats, and that Pg strains that co-express particular virulence factors (polysaccharide capsule and fimbriae) induce uterine atherosis that coincides with poor trophoblast invasion into the myometrium. Based on these features we propose that Pg promotes adverse pregnancy outcomes by colonizing the uterine stroma (before pregnancy) or the deep placental bed (during early pregnancy). Depending on the Pg virulence phenotype, the microbe induces uterine arteritis/atherosis, which during pregnancy, disrupts the physiologic process of uterine spiral artery remodeling resulting in abnormal placentation and promoting obstetric complications. The objectives of this application are to test our hypothesis using common human Pg isolates with varying virulence phenotypes in our rat model of chronic oral infection.
The aims of this proposal are 1) Define the Pg virulence phenotype that produces persistent uterine arteritis/atherosis in the non-pregnant uterus during chronic oral infection, and 2) Characterize the Pg induced inflammatory profile that results in poor extravillous trophoblast invasion, impaired spiral artery remodeling, and IUGR following chronic oral infection. Relevance to public health: This application address a significant problem in perinatal medicine referred to as defective deep placentation, which occurs in several obstetrical syndromes including miscarriages, intrauterine growth retardation (IUGR), preeclampsia, and preterm birth. Therefore, elucidating the early pathologic events that disrupt physiologic remodeling of the spiral arteries is a research priority since this could lead o the development of novel methods that may prevent placental bed disorders or improve early detection of individuals at risk for this syndrome.
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|Phillips, Priscilla; Brown, Mary B; Progulske-Fox, Ann et al. (2018) Porphyromonas gingivalis strain-dependent inhibition of uterine spiral artery remodeling in the pregnant rat. Biol Reprod 99:1045-1056|
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