Porphyromonas gingivalisInfection in Pregnant Mice Is Associated with Placental Dissemination, an Increase in the Placental Th1/Th2 Cytokine Ratio, and Fetal Growth Restriction

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Abstract
Our previous animal studies showed that maternalPorphyromonas gingivalisinfection in a subcutaneous chamber is associated with hepatic and uterine translocation, as well as systemic induction of maternal inflammatory responses, both of which were associated with fetal growth restriction (FGR). However,P. gingivalis-challenged dams had fetuses with either FGR (2 standard deviations below mean weight of nonchallenged dams) or normal weight. Therefore, the objective of this study was to determine whether maternal infection withP. gingivaliscompromises normal fetal development via direct placental invasion and induction of fetus-specific placental immune responses characterized by a proinflammatory Th1-type cytokine profile.P. gingivalis-specific DNA was detected in placentas and fetuses of FGR and normal littermates fromP. gingivalis-infected dams. Th1- and Th2-type cytokine mRNA as well as tumor necrosis factor alpha and transforming growth factor β2 mRNA were examined in placental tissue by using reverse transcription-PCR to determine Th1/Th2 ratios. For eight litters containing both normal-weight and FGR fetuses,P. gingivalisDNA was detected only in the placentas of FGR fetuses. All fetuses and all amniotic fluid samples from infected and control dams were negative forP. gingivalisDNA. mRNA levels of gamma interferon and interleukin-2 (IL-2) were significantly increased in placentas of FGR fetuses, while expression of IL-10 was significantly decreased in the same group. These data indicate that, inP. gingivalis-challenged dams, within each litter there is placenta-specific translocation ofP. gingivalisthat results in growth restriction of the targeted fetus, which is associated with a shift in the placental Th1/Th2 cytokine balance.