Lipopolysaccharide (LPS)‐Induced Intra‐Uterine Fetal Death (IUFD) in Mice Is Principally Due to Maternal Cause but Not Fetal Sensitivity to LPS

Kohmura, Yasuhiro; Kirikae, Teruo; Kirikae, Fumiko; Nakano, Masayasu; Sato, Ikuo

doi:10.1111/j.1348-0421.2000.tb02581.x

Cited by 71 publications

(51 citation statements)

References 38 publications

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“…The effects of microbial infections on pregnancy outcomes have been observed in all mammalian species, including humans, and have been extensively studied in several animal models (6,30). Other studies suggest that some adverse pregnancy outcomes are associated with subclinical infections such as periodontitis.…”

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confidence: 99%

Porphyromonas gingivalisInfection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice

Lin¹,

Smith

Champagne³

et al. 2003

Infect Immun

119

117

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Epidemiological studies have shown a potential association between maternal periodontitis and pregnancy complications. We used a pregnant murine model to study the effect of infection with the periodontal pathogen Porphyromonas gingivalis on pregnancy outcomes. Female BALB/c mice were inoculated with heat-killed P. gingivalis (10 9 CFU) in a subcutaneous chamber and mated 2 weeks later. At gestation day (GD) 7.5, mice were challenged with live P. gingivalis ( Maternal liver, uterus, and spleen samples were examined for P. gingivalis DNA using a PCR technique. Of the eight challenged mice with FGR fetuses, three had PCR signals for P. gingivalis in liver and uterus, but not in the spleen. Liver, uterus, and spleen were negative for P. gingivalis DNA among all other challenged and control mice. In serum of dams with FGR fetuses, tumor necrosis factor alpha levels were elevated significantly, while interluekin-10 levels were significantly reduced compared to levels in dams with normal fetuses. P. gingivalis-specific serum immunoglobulin G levels were significantly elevated in dams with FGR fetuses compared to dams without any FGR fetuses. These data demonstrate that P. gingivalis-induced murine FGR is associated with systemic dissemination of the organism and activated maternal immune and inflammatory responses.

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mentioning

confidence: 99%

Porphyromonas gingivalisInfection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice

Lin¹,

Smith

Champagne³

et al. 2003

Infect Immun

119

117

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“…28 TLR4 expression has been reported in the neonatal 29,30 and adult rat brain, 31 and LPS can induce cytokine expression in glial and neuronal cultures prepared from human, murine and rat fetal brain; [32][33][34][35][36] however, it remains controversial whether transplacental transfer of LPS occurs in rodents in vivo. 37,38 The aim of the present study therefore was to investigate the distribution and site of action of LPS (i.e. fetal, placental and/or maternal) in order to elucidate whether behavioral changes observed in the adult offspring of dams infected during pregnancy are mediated via the direct, or indirect, action of LPS on the fetal brain.…”

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confidence: 99%

The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia

et al. 2005

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Maternal infections with bacterial or viral agents during pregnancy are associated with an increased incidence of schizophrenia in the offspring at adulthood although little is known about the mechanism by which maternal infection might affect fetal neurodevelopment. Exposure of pregnant rodents to the bacterial endotoxin, lipopolysaccharide (LPS), results in behavioral deficits in the adult offspring that are relevant to schizophrenia. It is however unknown whether these effects are due to the direct action of the inflammatory stimulus on the developing fetus, or due to secondary immune mediators (cytokines) activated at maternal/ fetal sites. In this study we sought to elucidate the site of action of LPS, following a single intraperitoneal (i.p.) injection, in pregnant rats at gestation day 18. Animals received 5 lCi of iodinated LPS ( 125 I-LPS) and its distribution was assessed in maternal/fetal tissues (1-8 h). In addition, induction of the inflammatory cytokines, TNF-a, IL-1b and IL-6, was measured in maternal/fetal tissues following maternal LPS challenge (0.05 mg/kg, i.p.) (2-8 h). 125I-LPS was detected in maternal tissues and placenta, but not the fetus. This distribution was accompanied by significant increases in TNF-a, IL-1b and IL-6 in maternal plasma and placenta, but not in fetal liver or brain. A significant increase in IL-1b was however detected in fetal plasma, possibly due to transfer from the maternal circulation or placenta. Collectively, these data suggest that effects of maternal LPS exposure on the developing fetal brain are not mediated by the direct action of LPS, but via indirect actions at the level of the maternal circulation or placenta.

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“…The cytokines, in turn, initiate the synthesis of secondary mediators, e.g., prostaglandins and matrix metalloproteinases involved in the preterm delivery (2,4). It has been proposed that fetal death results from a maternal response rather than fetal sensitivity to LPS (12,13).…”

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confidence: 99%

Maternal Endotoxin-Induced Preterm Birth in Mice: Fetal Responses in Toll-Like Receptors, Collectins, and Cytokines

et al. 2008

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Major cause of prematurity is spontaneous preterm birth (PTB) associated with intrauterine inflammation. Our aim was to establish a model of endotoxin Lipopolysaccharide-induced PTB of live-born pups and to study early immune activation in fetal and maternal compartments. Expression of several proteins that bind microbes (Toll-like receptors TLR4, TLR2; surfactant proteins SP-A, SP-D) was analyzed. At 16 or 17 d of gestation, C57BL/6 dams received a single dose of intraperitoneal LPS, leading to PTB within 17 h. Cytokine levels increased in maternal serum, followed by a modest increase in fetal serum and in amniotic fluid. In uterus, placenta, and fetal membranes, LPS mostly increased the expressions of TLR, SPs, and cytokines. The number of TLR2-positive macrophages increased in labyrinthine placenta. In fetal lung, intestine, liver, and brain there were modest changes in cytokine expressions. In fetal lung, SP and TLR mRNAs decreased and TLR2-positive macrophages redistributed around vessels. LPS-induced fetal deaths associated with early age (16 d gestation) rather than with proinflammatory activation. Here we propose that maternal LPS response leads to PTB and acute decrease of immune proteins in epithelial lining of fetal lung. Instead, acceleration of lung maturity has been previously observed in intraamniotic inflammation. (Pediatr Res 63: 280-286, 2008) P rematurity is the main cause of perinatal morbidity and mortality in developed countries. Altogether, 50 -70% of preterm births (PTBs) in humans are due to spontaneous onset of premature labor (1). There is a strong relationship between systemic or intrauterine infection and preterm delivery. Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, causes PTB in animals and has been implicated as a factor triggering preterm labor in humans (2). Different model systems have been established to study the induced PTB in mammalian species (3,4). The inflammatory models applied to mice involve intraperitoneal, intrauterine, or intraamniotic administration of heat-killed bacteria or bacterial products (5-7). Depending on the dose, gestational age, and site of exposure, the consequences of LPS-induced inflammatory response are variable. However, the administration of LPS has mostly resulted in fetal death or the delivery of dead fetuses (6 -11).The proposed sequence of inflammatory mediators leading to preterm labor and delivery involves the production of proinflammatory cytokines in uterus, placental tissue, and fetal tissues as a response to bacterial toxins. The cytokines, in turn, initiate the synthesis of secondary mediators, e.g., prostaglandins and matrix metalloproteinases involved in the preterm delivery (2,4). It has been proposed that fetal death results from a maternal response rather than fetal sensitivity to LPS (12,13).The innate immune system involved in nonclonal host defense is likely to influence fetal outcome. Toll-like receptors (TLRs) and collectins serve as signaling receptors for pathogen-associated molecular patterns...

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Lipopolysaccharide (LPS)‐Induced Intra‐Uterine Fetal Death (IUFD) in Mice Is Principally Due to Maternal Cause but Not Fetal Sensitivity to LPS

Abstract: Abstract:The present study deals with whether lipopolysaccharide

Cited by 71 publications

References 38 publications

Porphyromonas gingivalisInfection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice

Porphyromonas gingivalisInfection during Pregnancy Increases Maternal Tumor Necrosis Factor Alpha, Suppresses Maternal Interleukin-10, and Enhances Fetal Growth Restriction and Resorption in Mice

The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia

Maternal Endotoxin-Induced Preterm Birth in Mice: Fetal Responses in Toll-Like Receptors, Collectins, and Cytokines

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