Prenatal exposure to lipopolysaccharide results in neurodevelopmental damage that is ameliorated by zinc in mice

Chua, Joanne S C; Cowley, Carina J; Manavis, Jim; Rofe, Allan M.; Coyle, Peter

doi:10.1016/j.bbi.2011.10.002

Cited by 41 publications

(32 citation statements)

References 64 publications

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“…According to an earlier report, injection with zinc sulfate reduced LPS-induced teratogenicity in mice (28). A recent study found that s.c. injection with zinc sulfate alleviated LPS-induced neurodevelopmental damage in fetal brain (29). Importantly, dietary zinc supplementation during pregnancy could reduce LPS-induced teratogenicity and cognitive impairments in offspring (45,46).…”

Section: Discussionmentioning

confidence: 99%

“…An earlier report showed that injection with zinc sulfate reduced LPS-induced teratogenicity in mice (28). A recent study found that s.c. injection with zinc sulfate alleviated LPS-induced neurodevelopmental damage in fetal brain (29). Nevertheless, the molecular mechanism of zinc-mediated protection against LPSinduced developmental toxicity remains obscure.…”

Section: Ipopolysaccharide Is a Toxic Component Of Cell Walls Inmentioning

confidence: 99%

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Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect

Chen

Zhao

Xue

et al. 2012

The Journal of Immunology

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LPS is associated with adverse developmental outcomes, including preterm delivery, fetal death, teratogenicity, and intrauterine growth restriction (IUGR). Previous reports showed that zinc protected against LPS-induced teratogenicity. In the current study, we investigated the effects of zinc supplementation during pregnancy on LPS-induced preterm delivery, fetal death and IUGR. All pregnant mice except controls were i.p. injected with LPS (75 μg/kg) daily from gestational day (GD) 15 to GD17. Some pregnant mice were administered zinc sulfate through drinking water (75 mg elemental Zn per liter) throughout the pregnancy. As expected, an i.p. injection with LPS daily from GD15 to GD17 resulted in 36.4% (4/11) of dams delivered before GD18. In dams that completed the pregnancy, 63.2% of fetuses were dead. Moreover, LPS significantly reduced fetal weight and crown–rump length. Of interest, zinc supplementation during pregnancy protected mice from LPS-induced preterm delivery and fetal death. In addition, zinc supplementation significantly alleviated LPS-induced IUGR and skeletal development retardation. Further experiments showed that zinc supplementation significantly attenuated LPS-induced expression of placental inflammatory cytokines and cyclooxygenase-2. Zinc supplementation also significantly attenuated LPS-induced activation of NF-κB and MAPK signaling in mononuclear sinusoidal trophoblast giant cells of the labyrinth zone. It inhibited LPS-induced placental AKT phosphorylation as well. In conclusion, zinc supplementation during pregnancy protects against LPS-induced fetal growth restriction and demise through its anti-inflammatory effect.

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Section: Discussionmentioning

confidence: 99%

Section: Ipopolysaccharide Is a Toxic Component Of Cell Walls Inmentioning

confidence: 99%

Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect

Chen

Zhao

Xue

et al. 2012

The Journal of Immunology

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“…However, to date, no report has indicated which dose of s.c. LPS is sufficient to trigger a response in the mother and fetus without causing death. A limited number of articles have been published studying the effects of zinc supplementation and teratogenicity after prenatal exposure to LPS [25,26,27]. However, no evidence has been reported on effects on intrauterine or neonatal mortality, litter size, or gestational length.…”

Section: Discussionmentioning

confidence: 99%

Effects of Subcutaneous LPS Injection on Gestational Length and Intrauterine and Neonatal Mortality in Mice

Lopez

Steinbusch²,

Rutten³

et al. 2015

Neuroimmunomodulation

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Background: Infection during pregnancy can predispose offspring to develop various psychiatric disorders such as depression in later life. In order to investigate the potential mechanisms underlying these associations, animal models of maternal infection have been employed. As such, lipopolysaccharide (LPS) has been commonly used to mimic a bacterial infection in pregnant mice. Objective: The original aim of our study was to investigate the effects of different doses of subcutaneous LPS administration on affective behavior in adult mouse offspring. In the present paper, however, we report that subcutaneous LPS administration has a profound impact on gestational length, litter size, and perinatal mortality in the offspring, even at a relatively low dose. Methods: Pregnant mice were randomly divided into 3 groups, receiving either a high (2 mg/kg) or a low (0.5 mg/kg) dose of LPS or phosphate-buffered saline by means of subcutaneous injection. Subsequently, the effects on gestational length, litter size, and perinatal mortality in the offspring were assessed. Results: After subcutaneous injection with a high dose of LPS, we observed a significant decrease in gestational length and an increase in neonatal mortality. When the low dose was administered, a tendency towards a reduced litter size was observed, most likely reflecting increased intrauterine mortality in response to prenatal maternal LPS exposure. Conclusions: We showed that subcutaneous administration of 2 mg/kg LPS to pregnant mice in the last phase of gestation should be avoided because of high offspring mortality rates, whereas subcutaneous injection of 0.5 mg/kg LPS seems to result in reabsorption of the fetuses.

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“…Tissue sections were then dehydrated in graded ethanol series and coverslips mounted by using DePex mounting media. Detection of apoptotic cells by TUNEL was performed on formalin-fixed, paraffin-embedded thymic lymphoma sections as previously described (32). Digital images were acquired by using a NanoZoomer (Hamamatsu).…”

mentioning

confidence: 99%

Loss of caspase-2 augments lymphomagenesis and enhances genomic instability in Atm -deficient mice

Puccini

Shalini

Voss

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Caspase-2, the most evolutionarily conserved member of the caspase family, has been shown to be involved in apoptosis induced by various stimuli. Our recent work indicates that caspase-2 has putative functions in tumor suppression and protection against cellular stress. As such, the loss of caspase-2 enhances lymphomagenesis in Eμ-Myc transgenic mice, and caspase-2 KO (Casp2 Casp2−/− mice also showed increased levels of aneuploidy. These observations suggest that the tumor suppressor activity of caspase-2 is linked to its function in the maintenance of genomic stability and suppression of oxidative damage. Given that ATM and caspase-2 are important components of the DNA damage and antioxidant defense systems, which are essential for the maintenance of genomic stability, these proteins may synergistically function in tumor suppression by regulating these processes.

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Prenatal exposure to lipopolysaccharide results in neurodevelopmental damage that is ameliorated by zinc in mice

Cited by 41 publications

References 64 publications

Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect

Zinc Supplementation during Pregnancy Protects against Lipopolysaccharide-Induced Fetal Growth Restriction and Demise through Its Anti-inflammatory Effect

Effects of Subcutaneous LPS Injection on Gestational Length and Intrauterine and Neonatal Mortality in Mice

Loss of caspase-2 augments lymphomagenesis and enhances genomic instability in Atm -deficient mice

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