Membrane inflammasome activation by choriodecidual Ureaplasma parvum infection without intra-amniotic infection in a Non-Human Primate model†.

Intrauterine infection is a significant cause of neonatal morbidity and mortality. Ureaplasma parvum is a microorganism commonly isolated from cases of preterm birth and preterm premature rupture of membranes (pPROM). However, the mechanisms of early stage ascending reproductive tract infection remain poorly understood. To examine inflammation in fetal (chorioamnionic) membranes we utilized a non-human primate (NHP) model of choriodecidual U. parvum infection. Eight chronically catheterized pregnant rhesus macaques underwent maternal-fetal catheterization surgery at ~105-112 days gestation and choriodecidual inoculation with U. parvum (105 CFU/mL, n =4) or sterile media (controls; n = 4) starting at 115-119 days, repeated at 5-day intervals until C-section at 136-140 days (term=167 days). The average inoculation to delivery interval was 21 days, and Ureaplasma infection of the amniotic fluid (AF) was undetectable in all animals. Choriodecidual Ureaplasma infection resulted in increased fetal membrane expression of MMP-9 and PTGS2, but did not result in preterm labor or increased concentrations of AF pro-inflammatory cytokines. However, membrane expression of inflammasome sensors, NLRP3, NLRC4, AIM2, and NOD2, and adaptor ASC (PYCARD) gene expression were significantly increased. Gene expression of IL-1ß, IL-18, IL-18R1  , CASPASE-1, and pro-CASPASE-1 protein increased with Ureaplasma infection. Downstream inflammatory genes MYD88 and NFκB (Nuclear factor kappa-light-chain-enhancer of activated B cells) were also significantly upregulated. These results demonstrate that choriodecidual Ureaplasma infection, can cause activation of inflammasome complexes and pathways associated with pPROM and preterm labor prior to microbes being detectable in the AF.

Streptococcus pyogenes infects human endometrium by limiting the innate immune response.

Group A Streptococcus (GAS), a Gram-positive human-specific pathogen, yields 517,000 deaths annually worldwide, including 163,000 due to invasive infections and among them puerperal fever. Before efficient prophylactic measures were introduced, the mortality rate for mothers during childbirth was approximately 10%; puerperal fever still accounts for over 75,000 maternal deaths annually. Yet, little is known regarding the factors and mechanisms of GAS invasion and establishment in postpartum infection. We characterized the early steps of infection in an ex vivo infection model of the human decidua, the puerperal fever portal of entry. Coordinate analysis of GAS behavior and the immune response led us to demonstrate that (a) GAS growth was stimulated by tissue products; (b) GAS invaded tissue and killed approximately 50% of host cells within 2 hours, and these processes required SpeB protease and streptolysin O (SLO) activities, respectively; and (c) GAS impaired the tissue immune response. Immune impairment occurred both at the RNA level, with only partial induction of the innate immune response, and protein level, in an SLO- and SpeB-dependent manner. Our study indicates that efficient GAS invasion of the decidua and the restricted host immune response favored its propensity to develop rapid invasive infections in a gynecological-obstetrical context.

Modulation of Death and Inflammatory Signaling in Decidual Stromal Cells following Exposure to Group B Streptococcus.

Group B Streptococcus (GBS) is an opportunistic bacterial pathogen that contributes to miscarriage, preterm birth, and serious neonatal infections. Studies have indicated that some multilocus sequence types (STs) of GBS are more likely to cause severe disease than others. We hypothesized that the ability of GBS to elicit varying host responses in maternal decidual tissue during pregnancy is an important factor regulating infection and disease severity. To address this hypothesis, we utilized an antibody microarray to compare changes in production and activation of host signaling proteins in decidualized telomerase-immortalized human endometrial stromal cells (dT-HESCs) following infection with GBS strains from septic neonates or colonized mothers. GBS infection increased levels of total and phosphorylated mitogen-activated protein kinase (MAPK) family members such as p38 and JNK and induced nuclear factor kappa B (NF-κB) pathway activation. Infection also altered the regulation of additional proteins that mediate cell death and inflammation in a strain-specific manner, which could be due to the observed variation in attachment to and invasion of the decidual stromal cells and ability to lyse red blood cells. Further analyses confirmed array results and revealed that p38 promotes programmed necrosis in dT-HESCs. Together, the observed signaling changes may contribute to deregulation of critical developmental signaling cascades and inflammatory responses following infection, both of which could trigger GBS-associated pregnancy complications.

The Unique Microbiome and Innate Immunity During Pregnancy.

A successful pregnancy depends on not only the tolerance of the fetal immune system by the mother but also resistance against the threat of hazardous microorganisms. Infection with pathogenic microorganisms during pregnancy may lead to premature delivery, miscarriage, growth restriction, neonatal morbidity, and other adverse outcomes. Moreover, the host also has an intact immune system to avoid these adverse outcomes. It is important to note the presence of normal bacteria in the maternal reproductive tract and the principal role of the maternal-placental-fetal interaction in antimicrobial immunity. Previous studies mainly focused on maternal infection during pregnancy. However, this review summarizes the new views on the study of the maternal microbiome and expounds the innate immune defense mechanism of the maternal vagina and decidua as well as how cytotrophoblasts and syncytiotrophoblasts recognize and kill bacteria in the placenta. Fetal immune systems, thought to be weak, also exhibit an immune defense function that is indispensable for maintaining the safety of the fetus. The skin, lungs, and intestines of the fetus during pregnancy constitute the main immune barriers. These findings will provide a new understanding of the effects of normal microbial flora and how the host resists harmful microbes during pregnancy. We believe that it may also contribute to the reference on the clinical prevention and treatment of gestational infection to avoid adverse pregnancy outcomes.

Decidual stromal cell-derived PGE2 regulates macrophage responses to microbial threat.

PROBLEM: Bacterial chorioamnionitis causes adverse pregnancy outcomes, yet host-microbial interactions are not well characterized within gestational membranes. The decidua, the outermost region of the membranes, is a potential point of entry for bacteria ascending from the vagina to cause chorioamnionitis. We sought to determine whether paracrine communication between decidual stromal cells and macrophages shaped immune responses to microbial sensing. METHOD OF STUDY: Decidual cell-macrophage interactions were modeled in vitro utilizing decidualized, telomerase-immortalized human endometrial stromal cells (dTHESCs) and phorbol ester-differentiated THP-1 macrophage-like cells. The production of inflammatory mediators in response to LPS was monitored by ELISA for both cell types, while phagocytosis of bacterial pathogens (Escherichia coli and Group B Streptococcus (GBS)) was measured in THP-1 cells or primary human placental macrophages. Diclofenac, a non-selective cyclooxygenase inhibitor, and prostaglandin E2 (PGE2 ) were utilized to interrogate prostaglandins as decidual cell-derived paracrine immunomodulators. A mouse model of ascending chorioamnionitis caused by GBS was utilized to assess the colocalization of bacteria and macrophages in vivo and assess PGE2 production. RESULTS: In response to LPS, dTHESC and THP-1 coculture demonstrated enhancement of most inflammatory mediators, but a potent suppression of macrophage TNF-α generation was observed. This appeared to reflect a paracrine-mediated effect of decidual cell-derived PGE2 . In mice with GBS chorioamnionitis, macrophages accumulated at sites of bacterial invasion with increased PGE2 in amniotic fluid, suggesting such paracrine effects might hold relevance in vivo. CONCLUSION: These data suggest key roles for decidual stromal cells in modulating tissue responses to microbial threat through release of PGE2 .

Proteomic profiling of human decidual immune proteins during Toxoplasma gondii infection.

A Toxoplasma gondii infection during pregnancy can result in spontaneous abortion, preterm labor, or congenital fetal defects. The decidual immune system plays a critical role in regulating the immune micro-environment and in the induction of immune tolerance. To better understand the factors that mediate the decidual immune response associated with the T. gondii infection, a large-scale study employing TMT proteomics was conducted to characterize the differential decidual immune proteomes from infected and uninfected human decidual immune cells samples. The decidual immune cells from 105 human voluntary abortion tissues were purified, and of the 5510 unique proteins identified, 181 proteins were found to be differentially abundant (>1.2-fold cutoff, p < 0.05) in the T. gondii-infected decidual immune cells. 11 proteins of 181 differentially expressed proteins associated with trophoblast invasion, placental development, intrauterine fetal growth, and immune tolerance were verified using a quantitative real-time polymerase chain reaction and western blotting. This systematic analysis for the proteomics of decidual immune cells identified a broad range of immune factors in human decidual immune cells, shedding a new insight into the decidual immune molecular mechanism for abnormal pregnancy outcomes associated with T. gondii infection.

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis.

The bacterial pathogen Listeria monocytogenes causes foodborne systemic disease in pregnant women, which can lead to preterm labor, stillbirth, or severe neonatal disease. Colonization of the maternal decidua appears to be an initial step in the maternal component of the disease as well as bacterial transmission to the placenta and fetus. Host-pathogen interactions in the decidua during this early stage of infection remain poorly understood. Here, we assessed the dynamics of L. monocytogenes infection in primary human decidual organ cultures and in the murine decidua in vivo A high inoculum was necessary to infect both human and mouse deciduas, and the data support the existence of a barrier to initial colonization of the murine decidua. If successful, however, colonization in both species was followed by significant bacterial expansion associated with an inability of the decidua to mount appropriate innate cellular immune responses. The innate immune deficits included the failure of bacterial foci to attract macrophages and NK cells, cell types known to be important for early defenses against L. monocytogenes in the spleen, as well as a decrease in the tissue density of inflammatory Ly6Chi monocytes in vivo These results suggest that the infectivity of the decidua is not the result of an enhanced recruitment of L. monocytogenes to the gestational uterus but rather is due to compromised local innate cellular immune responses.

Chlamydia trachomatis infection of human endometrial stromal cells induces defective decidualisation and chemokine release.

Miscarriage affects ~20% of pregnancies and maternal infections account for ~15% of early miscarriages. Chlamydia trachomatis (Ct) has been associated with miscarriage but the underlying mechanisms are unknown. Successful implantation requires endometrial stromal cell (ESC) decidualisation. Maintenance of pregnancy requires angiogenesis, establishment of the correct cellular milieu and trophoblast invasion, all of which involve the action of chemokines. Our objective was to determine whether Ct infection impacts upon ESC decidualisation and chemokine secretion. Human primary ESC were decidualised in-vitro, infected with Ct serovar E, and changes in expression of genes of interest were measured using RT-PCR, proteomic array and ELISA. We demonstrate for the first time that Ct can infect and proliferate in ESC. Expression of the decidualisation marker prolactin was decreased in Ct-infected ESC at both mRNA and protein levels. Ct infection altered the chemokine profile of decidualised ESC as shown by proteomic array. Chemokines CXCL12 and CXCL16, important for trophoblast invasion, were analysed further and expression was reduced in infected decidualised cells at mRNA and protein levels. Our data indicate that Ct infection of ESC impairs decidualisation and alters chemokine release. These findings at least partially explain how Ct infection could result in adverse pregnancy outcomes.

Abnormal Expression of TRAIL Receptors in Decidual Tissue of Chlamydia trachomatis-Infected Rats During Early Pregnancy Loss.

Chlamydia trachomatis is the scientific name of pathogenic bacteria causing infection that has been linked to spontaneous abortion. In this study, the expression pattern of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL; a cytokine related to cell apoptosis) and its receptors was monitored in the decidua of C trachomatis-infected pregnant rats during early gestation to investigate the potential role of this molecular system in C trachomatis-induced spontaneous abortion. The data showed that C trachomatis infection significantly altered the messenger RNA (mRNA) expression of the receptors; death receptor (DR) 4 and DR5 increased, but decoy receptor (DcR) 1 and DcR2 decreased. Consistent with mRNA data, immunohistochemical staining of TRAIL and its receptors indicated that both DR4 and DR5 protein levels were elevated in infected tissues, primarily, decidual cells, decidual vessel wall, and uterine glands, whereas DcR1 and DcR2 showed lower levels compared to the noninfected group. Although receptor expression was altered, there was no difference detected in TRAIL expression. The observed altered expression of TRAIL receptors in C trachomatis-infected rats compared to noninfected rats during the embryo implantation phase suggests a possible mechanism for spontaneous abortion due to apoptosis and therefore failed embryo implantation. In addition, the observed increase in caspase-3 levels in infected cells further supports this finding. Taken together, the data presented in this study suggests C trachomatis infection altered the expression of TRAIL receptors, thus representing a general mechanism for C trachomatis-induced spontaneous abortion in C trachomatis-infected rats during early pregnancy loss.

Membrane Vesicles of Group B Streptococcus Disrupt Feto-Maternal Barrier Leading to Preterm Birth.

Infection of the genitourinary tract with Group B Streptococcus (GBS), an opportunistic gram positive pathogen, is associated with premature rupture of amniotic membrane and preterm birth. In this work, we demonstrate that GBS produces membrane vesicles (MVs) in a serotype independent manner. These MVs are loaded with virulence factors including extracellular matrix degrading proteases and pore forming toxins. Mice chorio-decidual membranes challenged with MVs ex vivo resulted in extensive collagen degradation leading to loss of stiffness and mechanical weakening. MVs when instilled vaginally are capable of anterograde transport in mouse reproductive tract. Intra-amniotic injections of GBS MVs in mice led to upregulation of pro-inflammatory cytokines and inflammation mimicking features of chorio-amnionitis; it also led to apoptosis in the chorio-decidual tissue. Instillation of MVs in the amniotic sac also resulted in intrauterine fetal death and preterm delivery. Our findings suggest that GBS MVs can independently orchestrate events at the feto-maternal interface causing chorio-amnionitis and membrane damage leading to preterm birth or fetal death.

[DYNAMICS OF CHANGES IN THE NUMERICAL DENSITY OF PLACENTAL MACROPHAGES DURING UROGENITAL INFECTION IN EARLY PREGNANCY].

The changes in the numerical density of macrophages of maternal (basal decidua) and fetal (Kashchenko-Hofbauer cells) origin were studied in the placenta of women with opportunistic (Ureaplasma urealyticum and Mycoplasma hominis) and pathogenic (Chlamydia trachomatis) urogenital microflora. Histological study of placenta was performed and CD68-immunoreactive cells were detected immunohistochemically in the basal decidua and in the chorionic villi obtained during artificial abortions for non-medical reasons in the 6-8th week of pregnancy (n=136). The results showed no changes in the numerical density of macrophages of maternal origin and a significant decrease in the numerical density of macrophages in the stroma of the chorionic villi, which was associated in Chlamydial infection with a delayed, and in Ureaplasma and Mycoplasma infection - with an accelerated development of the villous tree.

Escherichia coli-induced temporal and differential secretion of heat-shock protein 70 and interleukin-1ß by human fetal membranes in a two-compartment culture system.

INTRODUCTION: Escherichia coli is recognized as an etiological bacteria associated with chorioamnionitis and the preterm premature rupture of fetal membranes. This pathological condition induces pro-inflammatory cytokines and degradative metalloproteinases, which are considered biological markers secreted in an acute stage of infection. Heat-shock proteins (HSPs) are an important component of the innate immunity response and are found in different pathological conditions. They have not been previously measured in human fetal membranes in response to infectious conditions. We hypothesized that the choriodecidual tissue and amniotic epithelium secreted temporal and differential Hsp-60, Hsp-70, and interleukin (IL)-1ß mediated by E. coli infection. METHODS: Fetal membranes were mounted in a two-compartment culture system and infected with two passes of live E. coli at different doses (10², 104, 105, and 106 colony-forming units (CFU)/mL) and intervals of incubation (3, 6, and 24 h). The culture medium was collected, and Hsp-60, Hsp-70, and IL-1ß were assessed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: After 3 and 6 h of infection, E. coli induced an increase in Hsp-70 secretion in the choriodecidual tissue. However, after 24 h of incubation, Hsp-70 was downregulated and we observed an increase in IL-1ß secretion. By contrast, E. coli induced a lower Hsp-60 secretion in the amnion compared to Hsp-70. DISCUSSION: Human fetal membranes responded actively to E. coli infection, with an increase in Hsp-70 during the first hours of infection. After 24 h, there was an increase in the liberation of IL-1ß.

sHLA-G involved in the apoptosis of decidual natural killer cells following Toxoplasma gondii infection.

This study aims to assess whether soluble HLA-G (sHLA-G) is involved in apoptosis of decidual natural killer (dNK) cells following Toxoplasma gondii infection. dNK cells or NK-92 cells were infected with T. gondii and co-cultured with trophoblast cells or BeWo cells. Infected co-cultured cells were treated without or with sHLA-G neutralizing antibody. Uninfected co-cultured cells were used as controls. Apoptosis of dNK cells were analyzed by flow cytometry and confocal microscope. Real-time PCR and Western blot were used to determine caspase 3 and caspase 8 expression. sHLA-G in supernatant were measured by enzyme-linked immunosorbent assay (ELISA). In infection groups, sHLA-G was increased, while dNK apoptosis proteins caspase 3 and caspase 8 were up-regulated, but significantly decreased in the presence of sHLA-G neutralizing antibody compared to controls. Under the situation of T. gondii-infected dNK cells co-cultured with trophoblast cells, the up-regulation of sHLA-G could induce dNK cells apoptosis which ultimately may contribute to the abnormal pregnancy outcomes with T. gondii infection.

Toll-like receptors at the maternal-fetal interface in normal pregnancy and pregnancy complications.

Toll-like receptors (TLRs) form the major family of pattern recognition receptors (PRRs) that are involved in innate immunity. Innate immune responses against microorganisms at the maternal-fetal interface may have a significant impact on the success of pregnancy, as intrauterine infections have been shown to be strongly associated with certain complications of pregnancy. At the maternal-fetal interface, TLRs are expressed not only in the immune cells but also in non-immune cells such as trophoblasts and decidual cells; moreover, their expression patterns vary according to the stage of pregnancy. Here, we will update potential functions of TLRs in these cells, their recognition and response to microorganisms, and their involvement in the innate immunity. The impact of TLR-mediated innate immune response will be discussed via animal model studies, as well as clinical observations.

Effect of oxygen tension on bacteria-stimulated cytokine production by fetal membranes.

AIM: Tissue culture studies indicate that bacterial products stimulate the production of proinflammatory cytokines by reproductive tissues. However, most of these studies have been performed under room air conditions, supplemented with 5% CO2. In this study, we tested whether O2 tension affects bacteria-stimulated cytokine production by extra-placental fetal membranes. METHODS: Cultures of full-thickness membranes, isolated choriodecidua, and isolated amnion were exposed to bacteria and incubated under 21% (room air) or 5% O2 for 18 h. Cytokine concentrations in conditioned medium was quantified by immunoassay. RESULTS: Culture under 5% O2 increased production of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, but reduced IL-10 and IL-6 production by full membranes. Isolated choriodecidua responded to 5% O2 with increased IL-1ß production and reduced IL-6 production, but had no effect on TNF-α and IL-10 production was not detected. No effect of O2 tension on IL-1ß or IL-6 production by isolated amnion was detected, however, Escherichia coli-stimulated IL-10, TNF-α and IL-8 production was enhanced by culture under 5% O2. CONCLUSIONS: Increased oxygen tension reduces the pro-inflammatory responsiveness of cell cultures to E. coli and promotes an anti-inflammatory cytokine profile. Differential effects of O2 tension on choriodecidua and amnion suggests a network of paracrine factors that regulate cytokine levels in response to changes in O2 tension.

Antimicrobial peptide response to group B Streptococcus in human extraplacental membranes in culture.

OBJECTIVE: Streptococcus agalactiae (GBS) is an important cause of chorioamnionitis. This study characterizes GBS colonization and stimulation of antimicrobial responses in human extraplacental membranes using an ex vivo transwell two-compartment system of full-thickness membranes and live GBS. STUDY DESIGN: Human extraplacental membranes were affixed to transwell frames (without synthetic membranes). Live GBS was added to the decidual side of membranes in transwell cultures, and cocultures were incubated for 4, 8 and 24 h. GBS recovery from homogenized membranes and culture medium was determined by enumerating colony forming units (CFU) on blood agar. Antimicrobial peptide expression was identified using immunohistochemistry and ELISA. GBS killing by HBDs was assessed in vitro by incubating GBS with different human beta defensins (HBDs) for 3 h, then enumerating CFU. RESULTS: GBS recovery from membranes markedly decreased over time (P < 0.05). The antimicrobial peptides HBD-1, HBD-2, HBD-3, and lactoferrin were expressed in both GBS-exposed and non-exposed tissues. Notably, a pattern of localized increased HBD-2 in the amnion of GBS-infected tissue was observed. Moreover, GBS-treated membranes released increased amounts of HBD-2 into the amniotic and decidual compartments of the transwell cultures after 24 h (P < 0.05). In bacterial cultures, HBD-2 decreased GBS viability in a concentration-dependent manner (P < 0.05). CONCLUSION: Innate immune responses in ex vivo human extraplacental membranes suppress GBS growth. HBD-2 was implicated in this GBS suppression with evidence of signal transduction across the tissue. Antimicrobial peptides may be important for innate immune defense against intrauterine GBS infections during pregnancy.

Preserved ex vivo inflammatory status in decidual cells from women with preterm labor and subclinical intrauterine infection.

OBJECTIVE: To compare the inflammatory response preserved ex vivo by decidual cells isolated from women who experienced preterm labor with and without subclinical intrauterine infection. METHODS: Fetal membranes were obtained after cesarean section from 35 women who delivered before 37 weeks of gestation following spontaneous preterm labor, with no clinical evidence of intrauterine infection. Decidua was microbiologically tested and cultured. Concentrations of anti-inflammatory cytokines (IL-2, IL-4, IL-10), pro-inflammatory cytokines (IL-6, IL-8, IL-1ß and TNF-α), and matrix metalloproteinases (MMP-1, MMP-2, MMP-3, MMP-7, MMP-8, MMP-9) were measured in the supernatants using Bio-Plex, and prostaglandin E(2) (PGE(2)) was measured by enzyme immunoassay. RESULTS: Subclinical infection was confirmed in 10 women (28.5%). Microorganisms isolated were Ureaplasma urealyticum (4), group B streptococci (3), Gardnerella vaginalis (1), and Escherichia coli (2). We found a significant increase of pro-inflammatory cytokines and a significant decrease of anti-inflammatory cytokines in supernatants from decidual cells obtained from women with preterm labor and subclinical intrauterine infection compared to women without infection. Secretion of MMP-1, MMP-8, MMP-9 and PGE(2) was significantly higher in infected women. Secretion of IL-8 by decidual cells from infected women persisted upon repeated in vitro culture passages. CONCLUSIONS: Almost 30% of idiopathic preterm labor cases were associated with subclinical intrauterine infection, and decidual cells isolated from these cases preserved an ex vivo inflammatory status after in vivo bacterial exposure.

An experimental mixed bacterial infection induced differential secretion of proinflammatory cytokines (IL-1ß, TNFα) and proMMP-9 in human fetal membranes.

Overall, 1-4% of all births in the US are complicated by choriamnionitis. Choriamnionitis is a polymicrobial infection most often due to ascending genital microbes which, in over 65% of positive amniotic fluid cultures, involves two or more organisms. In this study, we determine the cytokines expression (IL-1ß, TNFα) and prometalloproteinase activation (proMMP-2 and proMMP-9) after double o single infection an in vitro model of human fetal membranes. Fetal membranes at term were mounted in the Transwell culture system and after 24 h of infection, choriodecidual, and amnion media was collected. IL-1ß and TNFα were evaluated by ELISA, whereas proMMP-9 and proMMP-2 were determined by substrate gel zymography. The choriodecidual and amnion compartments actively respond to the infectious process, which induced the secretion of IL-1ß, TNFα, and proMMP-9 after either mixed or single infection. The proMMP-2 secretion profile was the same after all experimental conditions. There was no synergy between Streptococcus agalactiae and Escherichia coli for inducing the secretion of inflammatory factors or degradative metalloproteinase. In conclusion, these two bacteria could initiate different pathways to induce chorioamnioitis.

Innate inflammatory responses of human decidual cells to periodontopathic bacteria.

OBJECTIVE: The purpose of this study was to test the hypothesis that periodontopathic bacteria exert potent proinflammatory effects in human decidua. STUDY DESIGN: The immunostimulatory effects of Gram-positive and negative periodontopathic bacteria and their lipopolysaccharides were tested in human decidual cell cultures in comparison with Escherichia coli. Cytokine production was measured by enzyme-linked immunosorbent assay; inflammatory gene expression was measured by oligonucleotide arrays and quantitative real time-polymerase chain reaction. RESULTS: All bacteria that were tested elicited an inflammatory response, although concentration-dependence and efficacy varied considerably with organism and culture. Lipopolysaccharides were more potent stimuli than intact bacterial cells, although bacteria exerted greater effects at high concentrations. Of 112 genes on the arrays, 18 genes were stimulated significantly by one or more lipopolysaccharide preparation. CONCLUSION: The ability of periodontopathic bacteria to stimulate a decidual inflammatory response is highly variable and partly dependent on the presence and structure of constituent lipopolysaccharides. This adds to our understanding of the causal association between periodontal disease and preterm birth.

Localization of P. gingivalis in preterm delivery placenta.

Increasing evidence suggests an association between periodontal disease and adverse pregnancy outcomes. Although infection is considered as a risk factor for preterm delivery, the localization of oral bacteria or their antigens in chorioamnionitis placental tissue has never been demonstrated. This study was devised to test the hypothesis that periodontal pathogens may be present and affect human placenta in cases of chorioamnionitis. Using immunocytochemistry, we have identified the presence of Porphyromonas gingivalis antigens in placental tissues. The antigens were detected in the placental syncytiotrophoblasts, chorionic trophoblasts, decidual cells, and amniotic epithelial cells, as well as the vascular cells. There was a substantial increase in immunostaining intensity of the tissues sectioned from women with chorioamnionitis compared to those experiencing normalterm pregnancy, p < 0.019 (Mann-Whitney test). These results suggest that P. gingivalis may commonly colonize placental tissue, and that the presence of the organism may contribute to preterm delivery.