Relationship between endotoxin-induced abortion and the synthesis of prostaglandin F

Summary. Treatment of rabbits with indomethacin (10 mg/kg/day) 48 hr before mating, and with 20 mg/kg at 12 hr followed by 8 mg/kg at 48, 72 or 96 hr after mating did not affect the rate of egg transport through the oviduct. Indomethacin treatment at the time of implantation interfered with pregnancy and caused degeneration and resorption of embryos. These results suggest that inhibition of prostaglandin synthesis does not directly affect egg transport, but that prostaglandin appears to be required for the retention of implanted embryos.

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“…As shown in Table 2 Skarnes & Harper, 1972). One clear effect of indomethacin was its interference with normal pregnancy.…”

Section: Resultsmentioning

confidence: 99%

Effect of indomethacin on egg transport and pregnancy in the rabbit

El-Banna¹,

Sacher²,

Schilling³

1976

Reproduction

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“…Skarnes & Harper (1972) demonstrated increased levels of prostaglandins and inhibition of diarrhoea by indomethacin in a model involving the same dose and type of endotoxin as used in the present study. Since the substrate for the synthesis of the relevant prostaglandin is arachidonic acid, and the main source of arachidonic acid in mammalian tissues is the phospholipid esters, endotoxin diarrhoea must involve activation of the mechanism which releases this arachidonic acid prior to its metabolism to the diarrhoea-inducing prostaglandins.…”

Section: Discussionmentioning

confidence: 66%

“…Although intraperitoneal administration of endotoxin was effective, even at high doses, this route was never as effective as the intravenous one. Skarnes & Harper (1972) also used this route and dose of endotoxin to induce diarrhoea in mice. The onset of diarrhoea was more rapid with PGE2 and arachidonic acid than with endotoxin, but all three agents had produced their maximal incidence and severity of diarrhoea by 1.5 h after injection.…”

Section: Induction Of Diarrhoeamentioning

confidence: 99%

Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

Doherty¹

1981

British J Pharmacology

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Dexamethasone blocked endotoxin‐induced diarrhoea in mice, but not that induced by arachidonic acid or prostaglandin E2. Indomethacin blocked endotoxin and arachidonic acid‐induced diarrhoea, but not that induced by prostaglandin E2. Codeine blocked all three forms of diarrhoea. The above data, when considered in relation to literature reports that endotoxin induces prostaglandin synthesis, suggest that dexamethasone blocks diarrhoea by preventing the release of arachidonic acid, the substrate for prostaglandin biosynthesis. The activities of indomethacin and dexamethasone in castor oil diarrhoea support the above conclusion and their inactivity in 5‐hydroxytryptophan‐induced diarrhoea confirms the absence of ‘codeine‐like’ direct effects on the gut. Other glucocorticoids (hydrocortisone, prednisolone) were also able to block endotoxin diarrhoea, but oestradiol, testosterone and progesterone did not. The inhibitory action of dexamethasone on endotoxin diarrhoea could not be blocked by the protein synthesis inhibitor, cycloheximide, nor by the glucocorticoid receptor antagonist, progesterone. Thus, involvement of glucocorticoid receptor‐mediated gene activation could not be demonstrated.

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“…of exogenous progesterone delays the commencement of labor in mice (Skarnes and Harper, 1972). The importance of progesterone withdrawal for murine labor has been highlighted by the observed phenotypes of several genetically modified mouse lines.…”

Section: Dmmbiologistsorg 408mentioning

confidence: 99%

Preventing preterm birth: the past limitations and new potential of animal models

Ratajczak

Fay²,

Muglia

2010

Disease Models &Amp; Mechanisms

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The high rate of preterm birth in the USA and many other countries is a potential target for improving children's immediate health and reducing the medical problems they face as adults. The acute complications for infants born prematurely often require intensive care management and are followed by long-lasting cognitive, sensory, motor, and cardiovascular deficits that substantially limit adult capabilities and survival. The inability to effectively reduce preterm birth stems from the failure to understand normal mechanisms of parturition in humans. Although studies from several model organisms help define the physiology of maintenance and termination of pregnancy, there are fundamental differences between species. For example, species regulate their production of progesterone, the crucial hormone in sustaining pregnancy, differently. This limits the extent to which models can provide meaningful information about the physiological mechanisms of human gestation. The growing wealth of sequenced mammalian genomes, computational comparative genomic tools and systems biology approaches provides new potential to utilize the divergence of DNA sequences and physiology between species to understand the genetic underpinnings of preterm birth. Plunkett and Muglia, 2008). The association of these polymorphisms with disease is small and variable, but one emerging finding links racial differences in preterm birth frequency with a functional polymorphism in the promoter of a chaperone that is essential for collagen synthesis, SERPINH1. The mutation associated with preterm birth reduces the activity of the SERPINH1 promoter (Wang et al., 2006). This variant is increased in populations of African descent, and is associated with a 3.22-fold increase (95% confidence interval: 1.50-7.22) in the incidence of preterm birth associated with premature rupture of the fetal membranes. Disease Models & Mechanisms DMMSpontaneous idiopathic preterm birth may reflect acceleration of the normal gestational clock. Microarray data from uterine tissue reveals similar gene regulation patterns among women who labor prematurely and those who do not labor until their infants are full term (Bethin et al., 2003). The lack of distinguishing pathways between preterm and full-term gestation suggests that normal pathways may be accelerated in preterm birth. Thus, factors involved in normal pathway timing may be targets for predicting or preventing preterm birth.Infection deregulates the normal timing of parturition mechanisms. Mothers who deliver preterm infants, particularly at very early gestational ages, display an increased frequency of colonization with possibly pathologic microorganisms, even when they do not demonstrate overt evidence of infection (Watts et al., 1992;Onderdonk et al., 2008). Several animal models have been utilized to explore the normal timing mechanisms of parturition and the consequences of infection to elucidate pathways for preterm birth. Although they do not recapitulate the human disease in full, they do offer valuable insight...

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Relationship between endotoxin-induced abortion and the synthesis of prostaglandin F

Cited by 128 publications

References 28 publications

Effect of indomethacin on egg transport and pregnancy in the rabbit

Effect of indomethacin on egg transport and pregnancy in the rabbit

Inhibition of Arachidonic Acid Release as the Mechanism by Which Glucocorticoids Inhibit Endotoxin‐induced Diarrhoea

Preventing preterm birth: the past limitations and new potential of animal models

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