In vivo and in vitro developmental toxicity in LPS-induced zinc-deficient rabbits

Pitt, Jeffrey A.

doi:10.1016/s0890-6238(97)00060-9

Cited by 8 publications

(5 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although maternal Zn redistribution does occur following LPS exposure, these data suggest that Zn deficiency does not have a primary role in acute LPS embryolethality in mice. Similar results were observed in experiments on the role of Zn in LPS-induced embryolethality in rabbits by Pitt et al (1997). These investigators found a high incidence of embryo resorptions following maternal LPS exposure on either gd 8 or gd 10, and also observed a striking elevation of maternal hepatic MT (ϳ30-fold) as well as a drop in maternal plasma Zn within 24 h of LPS treatment.…”

Section: Discussionsupporting

confidence: 80%

See 1 more Smart Citation

The Embryolethality of Lipopolysaccharide in CD-1 and Metallothionein I-II Null Mice: Lack of a Role for Induced Zinc Deficiency or Metallothionein Induction

Leazer¹

2003

Toxicological Sciences

View full text Add to dashboard Cite

Lipopolysaccharide (LPS) is embryolethal in CD-1 mice. LPS induces metallothionein (MT) via cytokines, including TNF-alpha, IL-1, and IL-6, which initiate and maintain the acute phase response. Maternal hepatic MT induction in pregnant rats, by diverse toxicants, can result in maternal hypozincemia and subsequent embryonal zinc (Zn) deficiency. We examined the hypothesis that LPS causes embryo toxicity in CD-1 mice via MT induction and subsequent embryo Zn deficiency by (1) determining whether LPS induces maternal hepatic MT and causes Zn redistribution, (2) assessing the effects of maternal Zn supplementation on LPS developmental toxicity, and (3) assessing the role of MT with MT I-II null mice (MTKO). Timed pregnant CD-1 mice were dosed i.p. with LPS (S. typhimurium) (0.05 mg/kg) on gestation day (gd) 9. Zn supplementation was administered on gd 8 (10 mg/kg, pretreatment) or on gd 9 as a cotreatment (5 or 10 mg/kg). MTKO and wild type (WT) mice were dosed with LPS (0.05 or 0.1 mg/kg) on gd 9, and maternal liver MT and Zn and plasma Zn were measured. In CD-1 mice, maternal hepatic MT was elevated 24 h after LPS treatment, and cotreatment with Zn caused further elevation of MT. Maternal hepatic Zn concentrations paralleled hepatic MT concentrations. Maternal plasma Zn on gd 10 showed no consistent effect of LPS treatment or Zn cotreatment on gd 9. Zn pretreatment (10 mg/kg) on gd 8 did not ameliorate LPS embryolethality, while Zn cotreatment (5 or 10 mg/kg) on gd 9 exacerbated the toxicity of LPS. LPS produced a similar incidence of embryolethality in MTKO and WT strains on gd10. Plasma Zn concentrations were similar in both strains, while hepatic Zn concentrations were significantly higher in WT than in the MTKO strain. In conclusion, while LPS can induce maternal hepatic MT and Zn redistribution in CD-1 mice, this does not appear to be a key mechanism leading to LPS embryotoxicity.

show abstract

Section: Discussionsupporting

confidence: 80%

“…Cotreatment with Zn oxide on gd 8 did not reduce the incidence of LPS-induced resorptions, while cotreatment on gd 10 partially improved outcome, reducing the resorption incidence by 44%. Our treatment of CD-1 mice with LPS produced a much smaller induction of MT (ϳtwofold) than did treatment of rabbits by Pitt et al (1997).…”

Section: Discussionmentioning

confidence: 70%

The Embryolethality of Lipopolysaccharide in CD-1 and Metallothionein I-II Null Mice: Lack of a Role for Induced Zinc Deficiency or Metallothionein Induction

Leazer¹

2003

Toxicological Sciences

View full text Add to dashboard Cite

show abstract

“…Massive LPS administration has been shown to cause 100% mouse embryo loss during gestation (Aisemberg et al, 2013). Zn 2+ deficiency has been postulated to trigger LPS-induced increase of the rates of rabbit embryo loss (Pitt, Zoellner, & Carney, 1997). Even minimal doses of LPS can cause DNA damage in preimplantated embryos and maternal uterine cells, which might lead to abnormal embryo development and even ultimately inhibit implantation (Jaiswal, Jaiswal, Agrawal, & Chaturvedi, 2009).…”

mentioning

confidence: 99%

Microbiota‐derived lipopolysaccharide retards chondrocyte hypertrophy in the growth plate through elevating Sox9 expression

Cheng

Wang

et al. 2018

Journal Cellular Physiology

View full text Add to dashboard Cite

Accumulating data show that the cytotoxicity of bacterial lipopolysaccharides (LPS) from microbiota or infection is associated with many disorders observed in the clinics. However, it is still obscure whether or not embryonic osteogenesis is affected by the LPS exposure during gestation. Using the early chicken embryo model, we could demonstrate that LPS exposure inhibits chondrogenesis of the 8‐day chicken embryos by Alcian Blue‐staining and osteogenesis of 17‐day by Alcian Blue and Alizarin Red staining. Further analysis of the growth plates showed that the length of the proliferating zone (PZ) increases whereas that of the hypertrophic zone (HZ) decreased following LPS exposure. However there is no significant change on cell proliferation in the growth plates. Immunofluorescent staining, western blot analysis, and quantitive polymerase chain reaction revealed that Sox9 and Col2a1 are highly expressed at the messenger RNA level and their protein products are also abundant. LPS exposure causes a downregulation of Runx2 and Col10a1 expression in 8‐day hindlimbs, and a suppression of Runx2, Col10a1, and Vegfa expression in 17‐day phalanges. Knocking down Sox9 in ATDC5 cells by small interfering RNA transfection lead to the expression reduction of Col2a1, Runx2, and Col10a1, implying the vital role of Sox9 in the process of LPS‐induced delay in the transition from proliferating chondrocytes to hypertrophic chondrocytes in the growth plate. In the presence of LPS, the antioxidant defense regulator nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) is highly expressed, and the activities of superoxide dismutase 1 (SOD1), SOD2, and glutaredoxin rise in 17‐day phalanges and ADTC5 cells. Simultaneously, an increase of intracellular ROS is observed. When Nrf2 expression was knocked down in ATDC5 cells, the expressions of Sox9, Col2a1, Runx2, Col10a1, and Vegfa were also going down as well. Taken together, our current data suggest that LPS exposure during gestation could restrict the chondrocytes conversion from proliferating to hypertrophic in the growth plate, in which LPS‐induced Sox9 plays a crucial role to trigger the cascade of downstream genes by excessive ROS production and Nrf2 elevation.

show abstract

“…After that, the TLR4 signal transduction cascade activates the PI3K/Akt pathway and NF‐κB signaling to induce subsequent biological effects 13 . There are reports that massive LPS administration would cause 100% mouse embryo loss during gestation 14 ; LPS increased the rate of rabbit embryo loss via the pathogenesis of Zn deficiency 15 . Traces of LPS could cause DNA damage in preimplantation embryonic and maternal uterine cells, which might interfere with blastocyst implantation or later embryo malformation 16 .…”

Section: Introductionmentioning

confidence: 99%

Dysbacteriosis‐induced LPS elevation disturbs the development of muscle progenitor cells by interfering with retinoic acid signaling

et al. 2020

View full text Add to dashboard Cite

Whether myogenesis is affected by the maternal gut dysbacteriosis still remains ambiguous. In this study, first we show the elevated level of lipopolysaccharides (LPS) in a gut microbiota dysbiosis mouse model. Second, we demonstrate that the diameter of muscle fibers, limb development, and somitogenesis were inhibited in both the gut microbiota dysbiosis and LPS exposed mice and chicken embryos. These might be due to LPS disturbed the cell survival and key genes which regulate the somitogenesis and myogenesis. RNA sequencing and subsequent validation experiments verified that retinoic acid (RA) signaling perturbation was mainly responsible for the aberrant somite formation and differentiation. Subsequently, we found that LPS‐induced reactive oxygen species (ROS generation and antioxidant genes such as Nrf2, AKR1B10) contributed to the above ‐mentioned interference with RA signaling. These findings highlight that the gut microbiota homeostasis is also involved in regulating the development of muscle progenitor cells during pregnancy.

show abstract

In vivo and in vitro developmental toxicity in LPS-induced zinc-deficient rabbits

Cited by 8 publications

References 37 publications

The Embryolethality of Lipopolysaccharide in CD-1 and Metallothionein I-II Null Mice: Lack of a Role for Induced Zinc Deficiency or Metallothionein Induction

The Embryolethality of Lipopolysaccharide in CD-1 and Metallothionein I-II Null Mice: Lack of a Role for Induced Zinc Deficiency or Metallothionein Induction

Microbiota‐derived lipopolysaccharide retards chondrocyte hypertrophy in the growth plate through elevating Sox9 expression

Dysbacteriosis‐induced LPS elevation disturbs the development of muscle progenitor cells by interfering with retinoic acid signaling

Contact Info

Product

Resources

About