Effect of Salmonella Endotoxin Administered to the Pregnant Sheep at 133–142 Days Gestation on Fetal Oxygenation, Maternal and Fetal Adrenocorticotropic Hormone and Cortisol, and Maternal Plasma Tufnor Necrosis Factor α Concentrations1

Schlafer, Donald H.; Yuh, Bertrum; Foley, George L.; Elssaser, T H; Sadowsky, Drew W.; Nathanielsz, Peter W.

doi:10.1095/biolreprod50.6.1297

Cited by 42 publications

(30 citation statements)

References 40 publications

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“…Endotoxin-induced pregnancy losses associated with embryonic death, abortion, preterm labor and delivery have been documented in a number of species (Edqvist et al 1984, Fredriksson et al 1986, Giri et al 1990, Schlafer et al 1994. However, the mechanism of LPS-induced abortion is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

A ‘minimum dose’ of lipopolysaccharide required for implantation failure: assessment of its effect on the maternal reproductive organs and interleukin-1α expression in the mouse

Deb¹,

Chaturvedi²,

Jaiswal³

2004

Reproduction

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Genital tract infections caused by gram-negative bacteria induce abortion and are one of the most common complications of human pregnancy. This study was carried out to decipher the mechanism of gram-negative bacterial lipopolysaccharide (LPS)-induced pregnancy loss, using a mouse (Park strain) model. Since many of the biological effects of LPS are mediated by interleukin (IL)-1a, the role of IL-1a in LPS-induced pregnancy loss was studied. Pregnant female animals were injected intraperitoneally (i.p.) with different doses (1 to 50 mg) of LPS from Salmonella minnesota Re-595, on day 0.5 of pregnancy. We found that 250 mg/kg body weight (i.e. 5 mg/female mouse) of LPS when given on day 0.5 of pregnancy was the 'minimum dose' (MD) required to completely inhibit the implantation of the blastocyst in the mouse. The effect of this dose on the pathophysiology of the various reproductive organs (i.e. uterus, ectoplacental cones, developing fetus, ovaries etc.) was assessed on day 14 of pregnancy. The effects of this dose on the level and pattern of expression of the proinflammatory cytokine IL-1a in the maternal uterine horns and preimplantation stage embryos were studied by RT-PCR. A single dose (100 ng/mouse) of recombinant mouse IL-1a was given i.p. to pregnant females on day 1 of pregnancy to study its effect on implantation. Our results show that treatment of the pregnant animals with LPS may alter cell proliferation and induce leukocyte infiltration, degeneration of luminal glandular epithelium, and hyperplasia in the various reproductive organs, and may also alter both embryonic and uterine IL-1a expression. IL-1a administration also caused implantation failure similar to that of LPS. The observations suggest that the determined MD of LPS may alter the expression of developmentally important proinflammatory cytokines such as IL-1a, which could, in turn, inhibit the normal processes of blastocyst implantation. Therefore, it is proposed that the LPS-induced histopathological alterations in the various reproductive organs of pregnant animals could be mediated by IL-1a and this may be one of the causes of failure of blastocyst implantation in the mouse.

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Section: Discussionmentioning

confidence: 99%

A ‘minimum dose’ of lipopolysaccharide required for implantation failure: assessment of its effect on the maternal reproductive organs and interleukin-1α expression in the mouse

Deb¹,

Chaturvedi²,

Jaiswal³

2004

Reproduction

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“…Animal models used to investigate the mechanisms whereby infection causes PTB have included the mouse, 9-12 rat, 13,14 rabbit, 15 sheep, 16 guinea pig, 17,18 and monkey. 19,20 Infectioninduced PTB can be caused by systemic or local administration of a bacterial product such as lipopolysaccharide (LPS) or endotoxin.…”

Section: Introductionmentioning

confidence: 99%

An imbalance between innate and adaptive immune cells at the maternal–fetal interface occurs prior to endotoxin-induced preterm birth

et al. 2015

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“…Clinically, it is not clear how much and by which route endotoxins enter the fetal circulation, but it is likely that the fetus is usually exposed to quite small amounts of endotoxin. In fetal sheep, doses of LPS Ͼ1 g/kg can be fatal (27), whereas doses of 1-100 g/kg are often used in studies of the adult laboratory animal (16,28). In this study, using a low dose of LPS (0.1 g/kg) that produced only transient effects on fetal pH and blood gas parameters, we found that LPS caused changes of cerebral COX-2 expression and penetration of endogenous albumin and peripheral macrophages into the brain.…”

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confidence: 99%

Cerebrovascular Responses in the Fetal Sheep Brain to Low-Dose Endotoxin

et al. 2004

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Clinical and experimental evidence indicate that infection in pregnancy is associated with fetal brain damage. However, the inflammatory processes that compromise the fetal brain are not fully understood. In this study, we used a single, low dose of lipopolysaccharide (LPS, 0.1 g/kg i.v.) to provoke an acutephase response in unanesthetized fetal sheep in utero. COX-2 mRNA was increased in the cortex and cerebellum at 24 and 48 h after LPS, and immunoreactive COX-2 protein was increased in perivascular cells throughout gray and white matter at 24 h after LPS administration. Plasma albumin was observed in the parenchyma of the brain in cortex, thalamus, hypothalamus, corpus callosum, fornix, hippocampus, midbrain, subcallosal bundle, and cerebellar Purkinje cells. Large, rounded, lectin-positive cells with the appearance of macrophages were observed around blood vessels in subventricular white matter. These results indicate that blood-brain barrier permeability is increased in the fetal brain after exposure to endotoxin and suggests that cytotoxic and pro-inflammatory substances could pass from the circulation into the brain after peripheral inflammatory stimulation. There is a strong association between perinatal brain damage and intrauterine infection in human pregnancy (1). Infection is associated with histologic evidence of vascular inflammation of the umbilical cord (2), raised cytokine levels in amniotic fluid (3, 4), and increased incidence of white matter damage in the brain of the neonate (5). Nonetheless, the inflammatory responses provoked by infection in the fetus, and the events that lead to compromise of the fetal and neonatal brain, are poorly understood.Stimulation of the immune system by the bacterial endotoxin LPS leads to a series of host responses known as the acutephase reaction. The acute-phase reaction is mediated in large part by inflammatory cytokines (6). Cytokines in the circulation cross the BBB slowly and in amounts too small to stimulate inflammatory responses in the brain itself (7). However, cytokine receptors present on the luminal surface of the endothelial cells of cerebral blood vessels (8) may lead to stimulation of PG production on the basal side of the endothelial cell (9). This suggests that endothelial-derived PG could act on signal transduction pathways within the CNS, leading to the febrile response (10), changes of the sleep-wake cycle, and activation of the autonomic nervous system and hypothalamopituitary-adrenal axis (11).COX-1 and COX-2 are the rate-limiting enzymes for PG production from arachidonic acid. COX-1 is constitutively expressed in many cell types and is relatively unaffected by immune stimulation (12). In the adult brain, the constitutive synthesis of PG may be important for maintaining neuronal metabolism and synaptic function. COX-1 is localized to specific regions in fetal sheep brain, including some regions of cortex, hypothalamus, hippocampus, midbrain, pons, and medulla (13). In contrast to the COX-1 isoform, COX-2 expression is usually minimal unde...

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Effect of Salmonella Endotoxin Administered to the Pregnant Sheep at 133–142 Days Gestation on Fetal Oxygenation, Maternal and Fetal Adrenocorticotropic Hormone and Cortisol, and Maternal Plasma Tufnor Necrosis Factor α Concentrations1

Cited by 42 publications

References 40 publications

A ‘minimum dose’ of lipopolysaccharide required for implantation failure: assessment of its effect on the maternal reproductive organs and interleukin-1α expression in the mouse

A ‘minimum dose’ of lipopolysaccharide required for implantation failure: assessment of its effect on the maternal reproductive organs and interleukin-1α expression in the mouse

An imbalance between innate and adaptive immune cells at the maternal–fetal interface occurs prior to endotoxin-induced preterm birth

Cerebrovascular Responses in the Fetal Sheep Brain to Low-Dose Endotoxin

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